Introduction to Biopharmaceutics: Emergence, Evolution and Application
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About This Presentation
Biopharmaceutics Lecture 1
Instructor: Baasir Umair Khattak (MPhil Pharmacology, QAU)
Topic: The Emergence and Evolution of Biopharmaceutics as a Distinct Discipline and Its Classical and Modern Applications
Description:
This lecture traces the birth and evolution of biopharmaceutics—a disciplin...
Slide Content
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
1
The Emergence and Evolution of Biopharmaceutics as a Distinct Discipline
and its Classical and Modern application
1. Introduction
The mid-20th century witnessed a critical realization: drugs do not act merely as chemical entities
but as formulations, and the way they are delivered profoundly affects their clinical performance.
Biopharmaceutics was introduced as a term by Gerhard Levy in the 1960s, reflecting the
recognition that a scientific framework was needed to connect dosage form properties with drug
availability and therapeutic outcome. Before this recognition, drug therapy was studied largely
through the dual lenses of clinical pharmacology (effects in humans) and pharmaceutical chemistry
(drug design and stability). However, unexplained variability in therapeutic outcomes across
different formulations created a gap that demanded its own discipline.
This review will outline how biopharmaceutics arose, how it differs from pharmacokinetics, and
why its establishment was necessary despite pharmacology’s existing coverage of PK and PD.
2. Historical Background
2.1 Early Pharmacokinetic Thinking
The first systematic attempts to quantify drug movement within the body date back to the 1920s.
Widmark and Tandberg (1924) developed mathematical models to describe alcohol kinetics in
blood, while Torsten Teorell (1937) proposed a physiological compartmental model of drug
distribution—often considered the true birth of pharmacokinetics. Later, F.H. Dost in the 1950s
formalized the field and popularized the term pharmacokinetics, describing it as the “quantitative
study of drug absorption, distribution, metabolism, and excretion (ADME).”
2.2 Emergence of Biopharmaceutics (1960s)
The term biopharmaceutics was introduced in the 1960s by Gerhard Levy, a visionary in drug
development and pharmacology. Levy, a Hungarian-born Canadian American pharmacologist and
biopharmaceutical scientist, is often regarded as the “father of biopharmaceutics.” His primary
concern was to explain why drugs with identical chemical compositions or doses could produce
very different therapeutic outcomes in patients. At the time, drug disposition was studied largely
under clinical pharmacology and medicinal chemistry, but Levy recognized that neither of these
fields fully addressed the interplay between drug formulation, release, absorption, and clinical
response. He realized that a new scientific lens was needed—one that could bridge pharmaceutical
technology and therapeutic action. Thus, the discipline of biopharmaceutics was born.
The early vision of Levy was anchored in clinical observations: two drugs, or even two dosage
forms of the same drug, often yielded different therapeutic profiles, despite being chemically
identical. Why did one brand of digoxin or theophylline work while another failed? Why did
patient variability persist even when doses were the same? Levy argued that the missing link was
1
The Emergence and Evolution of Biopharmaceutics as a Distinct Discipline
and its Classical and Modern application
1. Introduction
The mid-20th century witnessed a critical realization: drugs do not act merely as chemical entities
but as formulations, and the way they are delivered profoundly affects their clinical performance.
Biopharmaceutics was introduced as a term by Gerhard Levy in the 1960s, reflecting the
recognition that a scientific framework was needed to connect dosage form properties with drug
availability and therapeutic outcome. Before this recognition, drug therapy was studied largely
through the dual lenses of clinical pharmacology (effects in humans) and pharmaceutical chemistry
(drug design and stability). However, unexplained variability in therapeutic outcomes across
different formulations created a gap that demanded its own discipline.
This review will outline how biopharmaceutics arose, how it differs from pharmacokinetics, and
why its establishment was necessary despite pharmacology’s existing coverage of PK and PD.
2. Historical Background
2.1 Early Pharmacokinetic Thinking
The first systematic attempts to quantify drug movement within the body date back to the 1920s.
Widmark and Tandberg (1924) developed mathematical models to describe alcohol kinetics in
blood, while Torsten Teorell (1937) proposed a physiological compartmental model of drug
distribution—often considered the true birth of pharmacokinetics. Later, F.H. Dost in the 1950s
formalized the field and popularized the term pharmacokinetics, describing it as the “quantitative
study of drug absorption, distribution, metabolism, and excretion (ADME).”
2.2 Emergence of Biopharmaceutics (1960s)
The term biopharmaceutics was introduced in the 1960s by Gerhard Levy, a visionary in drug
development and pharmacology. Levy, a Hungarian-born Canadian American pharmacologist and
biopharmaceutical scientist, is often regarded as the “father of biopharmaceutics.” His primary
concern was to explain why drugs with identical chemical compositions or doses could produce
very different therapeutic outcomes in patients. At the time, drug disposition was studied largely
under clinical pharmacology and medicinal chemistry, but Levy recognized that neither of these
fields fully addressed the interplay between drug formulation, release, absorption, and clinical
response. He realized that a new scientific lens was needed—one that could bridge pharmaceutical
technology and therapeutic action. Thus, the discipline of biopharmaceutics was born.
The early vision of Levy was anchored in clinical observations: two drugs, or even two dosage
forms of the same drug, often yielded different therapeutic profiles, despite being chemically
identical. Why did one brand of digoxin or theophylline work while another failed? Why did
patient variability persist even when doses were the same? Levy argued that the missing link was
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
2
not pharmacology alone but rather how the dosage form interacted with the biological system to
control drug availability. His work essentially reframed the conversation: it was not enough to
know the drug’s chemical properties or its pharmacological target—one must also understand how
the formulation and biological environment shaped drug exposure.
This is why biopharmaceutical techniques initially grew out of clinical pharmacology and
pharmaceutical chemistry. Clinical pharmacologists were already concerned with the therapeutic
action of drugs in humans, while chemists focused on drug molecules themselves. Levy merged
these worlds, creating a discipline that studied what happens between drug formulation and drug
action. His emphasis was on the rate and extent of drug absorption, which made biopharmaceutics
a mechanistic bridge between chemistry, formulation science, and therapeutic pharmacology.
In more simple terms, it is everything that controls the availability of the drug: how the drug exits
the dosage form and travels to the systemic circulation (for systemically acting drugs) or to the
local site of action (for locally acting agents). It provides a link between the formulation and the
clinical performance of a drug. A mechanistic understanding of biopharmaceutics ensures that the
formulation is optimized in terms of exposure.
2.3 Why It Was Initially Considered Part of Clinical Pharmacology and Chemistry
Before biopharmaceutics was recognized as a separate subject, the subject matter was split:
Clinical pharmacology monitored blood levels and linked dose to response but paid little
attention to formulation variables.
Pharmaceutical chemistry focused on solubility, stability, and excipients, but often
without connecting these to clinical data.
Levy’s innovation was to merge these perspectives, giving birth to a new field that could
systematically answer formulation-related therapeutic failures.
MeSH Definition (1970s):
“The study of the physical and chemical properties of a drug and its dosage form as related to the
onset, duration and intensity of its action.”
Modern Definition:
In modern parlance, the term biopharmaceutics encompasses the science associated with the
physical/chemical properties of the drug product (including all components therein) and their
interactions with parameters linked to the route of administration that affect the rate and extent of
drug uptake or presence at the site for local action.
Widely Used Definitions of Biopharmaceutics
The most widely used definition is:
2
not pharmacology alone but rather how the dosage form interacted with the biological system to
control drug availability. His work essentially reframed the conversation: it was not enough to
know the drug’s chemical properties or its pharmacological target—one must also understand how
the formulation and biological environment shaped drug exposure.
This is why biopharmaceutical techniques initially grew out of clinical pharmacology and
pharmaceutical chemistry. Clinical pharmacologists were already concerned with the therapeutic
action of drugs in humans, while chemists focused on drug molecules themselves. Levy merged
these worlds, creating a discipline that studied what happens between drug formulation and drug
action. His emphasis was on the rate and extent of drug absorption, which made biopharmaceutics
a mechanistic bridge between chemistry, formulation science, and therapeutic pharmacology.
In more simple terms, it is everything that controls the availability of the drug: how the drug exits
the dosage form and travels to the systemic circulation (for systemically acting drugs) or to the
local site of action (for locally acting agents). It provides a link between the formulation and the
clinical performance of a drug. A mechanistic understanding of biopharmaceutics ensures that the
formulation is optimized in terms of exposure.
2.3 Why It Was Initially Considered Part of Clinical Pharmacology and Chemistry
Before biopharmaceutics was recognized as a separate subject, the subject matter was split:
Clinical pharmacology monitored blood levels and linked dose to response but paid little
attention to formulation variables.
Pharmaceutical chemistry focused on solubility, stability, and excipients, but often
without connecting these to clinical data.
Levy’s innovation was to merge these perspectives, giving birth to a new field that could
systematically answer formulation-related therapeutic failures.
MeSH Definition (1970s):
“The study of the physical and chemical properties of a drug and its dosage form as related to the
onset, duration and intensity of its action.”
Modern Definition:
In modern parlance, the term biopharmaceutics encompasses the science associated with the
physical/chemical properties of the drug product (including all components therein) and their
interactions with parameters linked to the route of administration that affect the rate and extent of
drug uptake or presence at the site for local action.
Widely Used Definitions of Biopharmaceutics
The most widely used definition is:
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
3
“The study of the influence of formulation on the therapeutic activity of a drug product.”
“Alternatively, it may be defined as a study of the relationship of the physical and chemical
properties of the drug and its dosage form to the biological effects observed following the
administration of the drug in its various dosage forms”
Biopharmaceutics is the study of basic and applied research that focuses on the interactions
between drugs and their physicochemical properties and dosage form, as well as their
pharmacokinetics and clinical responses in response to its administration(Shargel et al,2012).
3. Scientific Drivers for Biopharmaceutics
3.1 The Problem of Unexplained Variability
The core scientific driver was the observation that patients on the same drug, same dose, but
different formulations could experience therapeutic failure or toxicity. This variability could not
be explained by PK models alone because PK assumed a drug dose was already available for
absorption.
3.2 Dosage Form as a Determinant
Levy emphasized that the dosage form controls drug liberation, disintegration, dissolution, and
subsequent absorption. Biopharmaceutics thus begins before PK: it studies how the drug exits its
dosage form, a process not formally included in classical PK models.
3.3 Early Case Studies
Digoxin: Different brands and batches showed dramatic differences in dissolution rates,
leading to variability in plasma levels and toxicity.
Levodopa-Carbidopa: Formulation adjustments improved bioavailability,
revolutionizing Parkinson’s therapy.
Griseofulvin: Micronization of particles significantly increased bioavailability.
These cases made it clear that without a framework for formulation effects, pharmacology could
not fully explain therapeutic outcomes.
4. Differentiating Biopharmaceutics from Pharmacokinetics
4.1 Origins of Pharmacokinetics
Pharmacokinetics (from Teorell, 1937; Dost, 1953) deals with ADME once the drug is available
in the body. It models concentration–time profiles and generates parameters such as clearance,
volume of distribution, and half-life.
4.2 How Biopharmaceutics Differs
3
“The study of the influence of formulation on the therapeutic activity of a drug product.”
“Alternatively, it may be defined as a study of the relationship of the physical and chemical
properties of the drug and its dosage form to the biological effects observed following the
administration of the drug in its various dosage forms”
Biopharmaceutics is the study of basic and applied research that focuses on the interactions
between drugs and their physicochemical properties and dosage form, as well as their
pharmacokinetics and clinical responses in response to its administration(Shargel et al,2012).
3. Scientific Drivers for Biopharmaceutics
3.1 The Problem of Unexplained Variability
The core scientific driver was the observation that patients on the same drug, same dose, but
different formulations could experience therapeutic failure or toxicity. This variability could not
be explained by PK models alone because PK assumed a drug dose was already available for
absorption.
3.2 Dosage Form as a Determinant
Levy emphasized that the dosage form controls drug liberation, disintegration, dissolution, and
subsequent absorption. Biopharmaceutics thus begins before PK: it studies how the drug exits its
dosage form, a process not formally included in classical PK models.
3.3 Early Case Studies
Digoxin: Different brands and batches showed dramatic differences in dissolution rates,
leading to variability in plasma levels and toxicity.
Levodopa-Carbidopa: Formulation adjustments improved bioavailability,
revolutionizing Parkinson’s therapy.
Griseofulvin: Micronization of particles significantly increased bioavailability.
These cases made it clear that without a framework for formulation effects, pharmacology could
not fully explain therapeutic outcomes.
4. Differentiating Biopharmaceutics from Pharmacokinetics
4.1 Origins of Pharmacokinetics
Pharmacokinetics (from Teorell, 1937; Dost, 1953) deals with ADME once the drug is available
in the body. It models concentration–time profiles and generates parameters such as clearance,
volume of distribution, and half-life.
4.2 How Biopharmaceutics Differs
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
4
Biopharmaceutics, in contrast, focuses on the rate and extent of drug release from the dosage form
and its availability at the site of absorption. It is concerned with solubility, dissolution rate,
permeability, excipient interactions, particle size, and manufacturing processes—factors generally
outside the scope of pharmacokinetics.
4.3 Overlap Between the Two
The overlap lies in absorption:
Biopharmaceutics investigates how formulation influences absorption.
Pharmacokinetics quantifies absorption once it occurs.
4.4 Key Conceptual Distinction
Pharmacokinetics = “What the body does to the drug.”
Biopharmaceutics = “What the dosage form does to the drug before the body can act on
it.”
BIOPHARMACEUTIC PRINCIPLES
A. Physicochemical Properties
The physicochemical properties of a drug profoundly influence its absorption, distribution,
metabolism, and excretion (ADME) characteristics.
These parameters determine bioavailability, formulation design, therapeutic effectiveness, and
stability.
Below are the major physicochemical factors affecting drug dissolution and absorption.
1. Drug Dissolution
For most drugs with limited water solubility, the rate at which the solid drug enters into solution
(i.e., the rate of dissolution) is often the rate-limiting step in bioavailability. This means that the
rate at which a drug dissolves directly influences how quickly and how much of it becomes
available for absorption into systemic circulation.
The Noyes–Whitney equation describes the diffusion-controlled rate of drug dissolution (dm/dt;
i.e., the change in the amount of drug in solution with respect to time):
D = diffusion coefficient of the solute
A = surface area of the solid undergoing dissolution
δ = thickness of the diffusion layer
4
Biopharmaceutics, in contrast, focuses on the rate and extent of drug release from the dosage form
and its availability at the site of absorption. It is concerned with solubility, dissolution rate,
permeability, excipient interactions, particle size, and manufacturing processes—factors generally
outside the scope of pharmacokinetics.
4.3 Overlap Between the Two
The overlap lies in absorption:
Biopharmaceutics investigates how formulation influences absorption.
Pharmacokinetics quantifies absorption once it occurs.
4.4 Key Conceptual Distinction
Pharmacokinetics = “What the body does to the drug.”
Biopharmaceutics = “What the dosage form does to the drug before the body can act on
it.”
BIOPHARMACEUTIC PRINCIPLES
A. Physicochemical Properties
The physicochemical properties of a drug profoundly influence its absorption, distribution,
metabolism, and excretion (ADME) characteristics.
These parameters determine bioavailability, formulation design, therapeutic effectiveness, and
stability.
Below are the major physicochemical factors affecting drug dissolution and absorption.
1. Drug Dissolution
For most drugs with limited water solubility, the rate at which the solid drug enters into solution
(i.e., the rate of dissolution) is often the rate-limiting step in bioavailability. This means that the
rate at which a drug dissolves directly influences how quickly and how much of it becomes
available for absorption into systemic circulation.
The Noyes–Whitney equation describes the diffusion-controlled rate of drug dissolution (dm/dt;
i.e., the change in the amount of drug in solution with respect to time):
D = diffusion coefficient of the solute
A = surface area of the solid undergoing dissolution
δ = thickness of the diffusion layer
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
5
Cs = concentration of the solute at saturation (at the surface)
Cb = concentration of the drug in the bulk solution at time t
Interpretation:
This equation indicates that dissolution is faster when:
The surface area (A) is larger
The concentration gradient (Cs − Cb) is higher
The diffusion layer thickness (δ) is thinner
The diffusion coefficient (D) is greater (which is affected by temperature and solvent
viscosity)
Example: Drugs like griseofulvin and digoxin show dissolution-rate limited absorption due to their
poor solubility.
2. Drug Solubility in a Saturated Solution
Drug solubility in a saturated solution (see Chapter 2, IV) is a static (equilibrium) property.
The dissolution rate of a drug, however, is a dynamic property related to the rate of absorption.
Additional Insight:
Solubility represents how much drug can dissolve, while dissolution represents how fast it
dissolves.
A drug with high solubility but slow dissolution (e.g., certain crystalline drugs) may still
exhibit poor bioavailability.
Factors such as temperature, pH, presence of surfactants, and crystal form affect solubility.
3. Particle Size and Surface Area
Particle size and surface area are inversely related. As solid drug particle size decreases, the particle
surface area increases.
a. Influence on Dissolution
As described by the Noyes–Whitney equation, the dissolution rate is directly proportional to the
surface area.
An increase in surface area allows for greater contact between the solid drug particles and the
solvent, resulting in a faster dissolution rate (see III.A.1).
b. Limitation with Hydrophobic Drugs
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Cs = concentration of the solute at saturation (at the surface)
Cb = concentration of the drug in the bulk solution at time t
Interpretation:
This equation indicates that dissolution is faster when:
The surface area (A) is larger
The concentration gradient (Cs − Cb) is higher
The diffusion layer thickness (δ) is thinner
The diffusion coefficient (D) is greater (which is affected by temperature and solvent
viscosity)
Example: Drugs like griseofulvin and digoxin show dissolution-rate limited absorption due to their
poor solubility.
2. Drug Solubility in a Saturated Solution
Drug solubility in a saturated solution (see Chapter 2, IV) is a static (equilibrium) property.
The dissolution rate of a drug, however, is a dynamic property related to the rate of absorption.
Additional Insight:
Solubility represents how much drug can dissolve, while dissolution represents how fast it
dissolves.
A drug with high solubility but slow dissolution (e.g., certain crystalline drugs) may still
exhibit poor bioavailability.
Factors such as temperature, pH, presence of surfactants, and crystal form affect solubility.
3. Particle Size and Surface Area
Particle size and surface area are inversely related. As solid drug particle size decreases, the particle
surface area increases.
a. Influence on Dissolution
As described by the Noyes–Whitney equation, the dissolution rate is directly proportional to the
surface area.
An increase in surface area allows for greater contact between the solid drug particles and the
solvent, resulting in a faster dissolution rate (see III.A.1).
b. Limitation with Hydrophobic Drugs
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
6
With certain hydrophobic drugs, excessive particle size reduction does not always increase the
dissolution rate.
Small particles tend to reaggregate into larger particles to reduce the high surface free energy
produced by size reduction.
c. Prevention of Aggregation
To prevent the formation of aggregates, small drug particles are molecularly dispersed in agents
such as:
Polyethylene glycol (PEG)
Polyvinylpyrrolidone (PVP; povidone)
Dextrose
Example:
A molecular dispersion of griseofulvin in a water-soluble carrier such as PEG 4000 (Gris–PEG)
enhances its dissolution and bioavailability.
Additional Notes:
Micronization and nanosizing are industrial methods used to reduce particle size.
Solid dispersions and co-precipitation are strategies to improve dissolution of poorly
soluble drugs.
4. Partition Coefficient and Extent of Ionization
a. Partition Coefficient
The partition coefficient (P) of a drug is the ratio of its solubility at equilibrium in a nonaqueous
solvent (e.g., n-octanol) to that in an aqueous solvent (e.g., water; pH 7.4 buffer solution).
Hydrophilic drugs (higher water solubility) have faster dissolution rates.
Lipophilic drugs have poor water solubility and often rely on lipid absorption mechanisms.
Clinical Relevance:
The partition coefficient reflects lipid membrane permeability, critical for oral absorption and
blood-brain barrier penetration.
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With certain hydrophobic drugs, excessive particle size reduction does not always increase the
dissolution rate.
Small particles tend to reaggregate into larger particles to reduce the high surface free energy
produced by size reduction.
c. Prevention of Aggregation
To prevent the formation of aggregates, small drug particles are molecularly dispersed in agents
such as:
Polyethylene glycol (PEG)
Polyvinylpyrrolidone (PVP; povidone)
Dextrose
Example:
A molecular dispersion of griseofulvin in a water-soluble carrier such as PEG 4000 (Gris–PEG)
enhances its dissolution and bioavailability.
Additional Notes:
Micronization and nanosizing are industrial methods used to reduce particle size.
Solid dispersions and co-precipitation are strategies to improve dissolution of poorly
soluble drugs.
4. Partition Coefficient and Extent of Ionization
a. Partition Coefficient
The partition coefficient (P) of a drug is the ratio of its solubility at equilibrium in a nonaqueous
solvent (e.g., n-octanol) to that in an aqueous solvent (e.g., water; pH 7.4 buffer solution).
Hydrophilic drugs (higher water solubility) have faster dissolution rates.
Lipophilic drugs have poor water solubility and often rely on lipid absorption mechanisms.
Clinical Relevance:
The partition coefficient reflects lipid membrane permeability, critical for oral absorption and
blood-brain barrier penetration.
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
7
b. Extent of Ionization
Drugs that are weak acids or bases exist in both ionized and nonionized forms in solution. The
extent of ionization depends on the pKa of the drug and the pH of the environment.
The ionized form is more polar and thus more water soluble, whereas the nonionized form is more
lipid-soluble and readily crosses biological membranes.
This relationship is described by the Henderson–Hasselbalch equation:
Example:
Weak acids like aspirin are absorbed better in the stomach (acidic medium).
Weak bases like morphine are absorbed better in the intestine (alkaline medium).
5. Salt Formation
The choice of salt form for a drug depends on the desired physical, chemical, or pharmacologic
properties. Certain salts are designed to provide:
Slower dissolution, extended action, or controlled release
Greater stability or reduced irritation/toxicity
(1) Stability Considerations
Some soluble salt forms are less stable than the nonionized form.
Example: Sodium aspirin is less stable than aspirin in its acid form.
(2) Buffered Formulations
Solid dosage forms containing buffering agents may be formulated with the free acid form of the
drug (e.g., buffered aspirin):
7
b. Extent of Ionization
Drugs that are weak acids or bases exist in both ionized and nonionized forms in solution. The
extent of ionization depends on the pKa of the drug and the pH of the environment.
The ionized form is more polar and thus more water soluble, whereas the nonionized form is more
lipid-soluble and readily crosses biological membranes.
This relationship is described by the Henderson–Hasselbalch equation:
Example:
Weak acids like aspirin are absorbed better in the stomach (acidic medium).
Weak bases like morphine are absorbed better in the intestine (alkaline medium).
5. Salt Formation
The choice of salt form for a drug depends on the desired physical, chemical, or pharmacologic
properties. Certain salts are designed to provide:
Slower dissolution, extended action, or controlled release
Greater stability or reduced irritation/toxicity
(1) Stability Considerations
Some soluble salt forms are less stable than the nonionized form.
Example: Sodium aspirin is less stable than aspirin in its acid form.
(2) Buffered Formulations
Solid dosage forms containing buffering agents may be formulated with the free acid form of the
drug (e.g., buffered aspirin):
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
8
(a) The buffering agent forms an alkaline medium in the GIT, and the drug dissolves in situ.
(b) The dissolved salt diffuses into the bulk fluid, forms a fine precipitate that redissolves rapidly,
enhancing absorption.
(3) Effervescent Preparations
Effervescent granules or tablets contain the acid drug plus sodium bicarbonate, tartaric acid, or
citric acid, added to water before administration.
The excess sodium bicarbonate forms an alkaline solution that enhances drug dissolution while
carbon dioxide evolution aids dispersion.
(4) Solubility Trends
For weakly acidic drugs, potassium and sodium salts are more soluble than calcium,
magnesium, or aluminum salts.
For weak bases, hydrochloride, sulfate, citrate, and gluconate salts are highly water-
soluble, whereas estolate, napsylate, and stearate is less soluble.
6. Polymorphism
Polymorphism is the ability of a drug to exist in more than one crystalline form.
Different polymorphs show differences in melting point, solubility, and dissolution rate.
Amorphous (noncrystalline) forms usually dissolve faster than crystalline forms.
Example: Ritonavir and carbamazepine exhibit polymorphism, significantly affecting their
formulation performance and bioavailability.
7. Chirality
Chirality is the ability of a drug to exist as optically active stereoisomers (enantiomers).
Enantiomers often differ in pharmacokinetic and pharmacodynamic properties.
Example: Ibuprofen exists as R- and S-enantiomers; only the S-enantiomer is pharmacologically
active.When the racemic mixture is taken orally, the R-enantiomer undergoes presystemic
inversion in the gut to the active S-form.
Because inversion is site-specific and formulation-dependent, ibuprofen’s activity may
vary considerably.
Clinical Note: Many modern drugs are now marketed as single enantiomer formulations
(e.g., esomeprazole, levocetirizine) to improve safety and efficacy.
8. Hydrates
Drugs may exist in a hydrated (solvated) form or as an anhydrous molecule.
Their dissolution rates differ significantly.
Example:
The anhydrous form of ampicillin dissolves faster and is absorbed more rapidly than the
hydrated form.
Additional Example:
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(a) The buffering agent forms an alkaline medium in the GIT, and the drug dissolves in situ.
(b) The dissolved salt diffuses into the bulk fluid, forms a fine precipitate that redissolves rapidly,
enhancing absorption.
(3) Effervescent Preparations
Effervescent granules or tablets contain the acid drug plus sodium bicarbonate, tartaric acid, or
citric acid, added to water before administration.
The excess sodium bicarbonate forms an alkaline solution that enhances drug dissolution while
carbon dioxide evolution aids dispersion.
(4) Solubility Trends
For weakly acidic drugs, potassium and sodium salts are more soluble than calcium,
magnesium, or aluminum salts.
For weak bases, hydrochloride, sulfate, citrate, and gluconate salts are highly water-
soluble, whereas estolate, napsylate, and stearate is less soluble.
6. Polymorphism
Polymorphism is the ability of a drug to exist in more than one crystalline form.
Different polymorphs show differences in melting point, solubility, and dissolution rate.
Amorphous (noncrystalline) forms usually dissolve faster than crystalline forms.
Example: Ritonavir and carbamazepine exhibit polymorphism, significantly affecting their
formulation performance and bioavailability.
7. Chirality
Chirality is the ability of a drug to exist as optically active stereoisomers (enantiomers).
Enantiomers often differ in pharmacokinetic and pharmacodynamic properties.
Example: Ibuprofen exists as R- and S-enantiomers; only the S-enantiomer is pharmacologically
active.When the racemic mixture is taken orally, the R-enantiomer undergoes presystemic
inversion in the gut to the active S-form.
Because inversion is site-specific and formulation-dependent, ibuprofen’s activity may
vary considerably.
Clinical Note: Many modern drugs are now marketed as single enantiomer formulations
(e.g., esomeprazole, levocetirizine) to improve safety and efficacy.
8. Hydrates
Drugs may exist in a hydrated (solvated) form or as an anhydrous molecule.
Their dissolution rates differ significantly.
Example:
The anhydrous form of ampicillin dissolves faster and is absorbed more rapidly than the
hydrated form.
Additional Example:
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
9
Caffeine anhydrate shows a higher dissolution rate than its hydrated counterpart.
9. Complex Formation
A complex is formed by the reversible or irreversible association of two or more interacting
molecules or ions.
Chelates are complexes involving ringlike structures between ligands and metal ions.
Many biologically important molecules—hemoglobin, insulin, cyanocobalamin—are
chelates.
Drugs such as tetracyclines form chelates with divalent (Ca²⁺, Mg²⁺) and trivalent (Al³⁺, Bi³⁺)
metals.
Many drugs also adsorb on charcoal or clay (kaolin, bentonite) forming complexes.
Complexes can also form with proteins like albumin or α₁-acid glycoprotein.
a. Effects on Properties
Complex formation usually alters the physical and chemical characteristics of the drug:
(1) The chelate of tetracycline with calcium is less soluble and poorly absorbed.
(2) Aminophylline (a theophylline-ethylenediamine complex) is more water soluble and used
parenterally.
(3) Cyclodextrins form complexes with many drugs to increase solubility and stability.
b. Permeability
Large drug–protein complexes cannot cross cell membranes easily.
These complexes must dissociate to release the free drug for absorption or transport.
Summary Table: Physicochemical Properties and Their Impact
Property
Definition /
Mechanism
Key Equations /
Relations
Influence on Drug
Performance
Examples / Notes
Dissolution Rate
Rate of solid drug
entering solution
Noyes–Whitney
equation
Determines rate-
limited absorption
Griseofulvin, Digoxin
Solubility
Static property
(maximum solubility)
—
Affects dissolution
and absorption
Influenced by pH,
temperature
Particle Size
Smaller size → larger
surface area
∝ 1/size Faster dissolution Gris-PEG formulation
Partition
Coefficient (P)
Lipid/water solubility
ratio
P = Co/Cw
Determines membrane
permeability
Affects BBB penetration
9
Caffeine anhydrate shows a higher dissolution rate than its hydrated counterpart.
9. Complex Formation
A complex is formed by the reversible or irreversible association of two or more interacting
molecules or ions.
Chelates are complexes involving ringlike structures between ligands and metal ions.
Many biologically important molecules—hemoglobin, insulin, cyanocobalamin—are
chelates.
Drugs such as tetracyclines form chelates with divalent (Ca²⁺, Mg²⁺) and trivalent (Al³⁺, Bi³⁺)
metals.
Many drugs also adsorb on charcoal or clay (kaolin, bentonite) forming complexes.
Complexes can also form with proteins like albumin or α₁-acid glycoprotein.
a. Effects on Properties
Complex formation usually alters the physical and chemical characteristics of the drug:
(1) The chelate of tetracycline with calcium is less soluble and poorly absorbed.
(2) Aminophylline (a theophylline-ethylenediamine complex) is more water soluble and used
parenterally.
(3) Cyclodextrins form complexes with many drugs to increase solubility and stability.
b. Permeability
Large drug–protein complexes cannot cross cell membranes easily.
These complexes must dissociate to release the free drug for absorption or transport.
Summary Table: Physicochemical Properties and Their Impact
Property
Definition /
Mechanism
Key Equations /
Relations
Influence on Drug
Performance
Examples / Notes
Dissolution Rate
Rate of solid drug
entering solution
Noyes–Whitney
equation
Determines rate-
limited absorption
Griseofulvin, Digoxin
Solubility
Static property
(maximum solubility)
—
Affects dissolution
and absorption
Influenced by pH,
temperature
Particle Size
Smaller size → larger
surface area
∝ 1/size Faster dissolution Gris-PEG formulation
Partition
Coefficient (P)
Lipid/water solubility
ratio
P = Co/Cw
Determines membrane
permeability
Affects BBB penetration
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
10
Property
Definition /
Mechanism
Key Equations /
Relations
Influence on Drug
Performance
Examples / Notes
Ionization (pKa)
Weak acids/bases
ionization balance
Henderson–
Hasselbalch
pH-dependent
absorption
Aspirin (acid), Morphine
(base)
Salt Formation
Drug + acid/base form
salts
—
Alters solubility,
stability
Na⁺, K⁺ salts (acidic drugs);
HCl salts (basic drugs)
Polymorphism
Existence of multiple
crystal forms
—
Alters dissolution &
stability
Ritonavir, Carbamazepine
Chirality
Optical isomers with
distinct activity
— Alters PK/PD profile Ibuprofen (S-active)
Hydration
Anhydrous vs
hydrated forms
—
Affects dissolution
rate
Ampicillin anhydrate
Complexation
Drug + ligand/metal
association
—
Alters solubility &
absorption
Tetracycline–Ca²⁺,
Aminophylline
B. Drug product and delivery system formulation:
1. General considerations:
a. Design of the appropriate dosage form or delivery system depends on the:
Physical and chemical properties of the drug
Dose of the drug,
Route of administration
Type of drug delivery system desired
Desired therapeutic effect
Physiologic release of the drug from the delivery system
Bioavailability of the drug at the absorption site
Pharmacokinetics and pharmacodynamics of the drug.
b. Bioavailability:
The more complicated the formulation of the finished drug product (e.g., controlled-release tablet,
enteric-coated tablet, transdermal patch), the greater the potential for a bioavailability problem.
For example, the release of a drug from a peroral dosage form and its subsequent bioavailability
depend on the succession of rate processes.
These processes may include the following:
Attrition, disintegration, or disaggregation of the drug product
Dissolution of the drug in an aqueous environment
10
Property
Definition /
Mechanism
Key Equations /
Relations
Influence on Drug
Performance
Examples / Notes
Ionization (pKa)
Weak acids/bases
ionization balance
Henderson–
Hasselbalch
pH-dependent
absorption
Aspirin (acid), Morphine
(base)
Salt Formation
Drug + acid/base form
salts
—
Alters solubility,
stability
Na⁺, K⁺ salts (acidic drugs);
HCl salts (basic drugs)
Polymorphism
Existence of multiple
crystal forms
—
Alters dissolution &
stability
Ritonavir, Carbamazepine
Chirality
Optical isomers with
distinct activity
— Alters PK/PD profile Ibuprofen (S-active)
Hydration
Anhydrous vs
hydrated forms
—
Affects dissolution
rate
Ampicillin anhydrate
Complexation
Drug + ligand/metal
association
—
Alters solubility &
absorption
Tetracycline–Ca²⁺,
Aminophylline
B. Drug product and delivery system formulation:
1. General considerations:
a. Design of the appropriate dosage form or delivery system depends on the:
Physical and chemical properties of the drug
Dose of the drug,
Route of administration
Type of drug delivery system desired
Desired therapeutic effect
Physiologic release of the drug from the delivery system
Bioavailability of the drug at the absorption site
Pharmacokinetics and pharmacodynamics of the drug.
b. Bioavailability:
The more complicated the formulation of the finished drug product (e.g., controlled-release tablet,
enteric-coated tablet, transdermal patch), the greater the potential for a bioavailability problem.
For example, the release of a drug from a peroral dosage form and its subsequent bioavailability
depend on the succession of rate processes.
These processes may include the following:
Attrition, disintegration, or disaggregation of the drug product
Dissolution of the drug in an aqueous environment
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
11
Convection and diffusion of the drug molecules to the absorbing surface
Absorption of the drug across cell membranes into the systemic circulation
c. Th e rate-limiting step in the bioavailability of a drug from a drug product is the slowest step
in a series of kinetic processes.
For most conventional solid drug products (e.g., capsules, tablets), the dissolution rate is
the slowest, or rate-limiting, step for bioavailability.
For a controlled- or sustained-release drug product, the release of the drug from the
delivery system is the rate-limiting step.
2. Solutions:
Solutions are homogeneous mixtures of one or more solutes dispersed molecularly in a dissolving
medium (solvent).
Compared with other oral and peroral drug formulations, a drug dissolved in an aqueous
solution is in the most bioavailable and consistent form. Because the drug is already in
solution, no dissolution step is necessary before systemic absorption occurs. Peroral drug
solutions are often used as reference preparation for solid peroral formulations.
A drug dissolved in a hydroalcoholic solution (e.g., elixir) also has good bioavailability.
Alcohol aids drug solubility. However, when the drug is diluted by gastrointestinal tract
fluid and other gut contents (e.g., food), it may form a finely divided precipitate in the
lumen of the gastrointestinal tract. Because of the extensive dispersion and large surface
area of such finely divided precipitates, redissolution and subsequent absorption occur
rapidly.
A viscous drug solution (e.g., syrup) may interfere with dilution and mix with
gastrointestinal tract content. The solution decreases the gastric emptying rate and the rate
of transfer of drug solution to the duodenal region, where absorption is most efficient.
3. Suspensions:
Suspensions are dispersions of finely divided solid particles of a drug in a liquid medium in which
the drug is not readily soluble. Th e liquid medium of a suspension comprises a saturated solution
of the drug in equilibrium with the solid drug.
The bioavailability of the drug from suspensions may be like that of a solution because the
finely divided particles are dispersed and provide a large surface area for rapid dissolution.
On the other hand, a slow dissolution rate decreases the absorption rate.
Suspending agents are often hydrophilic colloids (e.g., cellulose derivatives, acacia,
xanthan gum) added to suspensions to increase viscosity, inhibit agglomeration, and
decrease the rate at which particles settle. Highly viscous suspensions may prolong gastric
emptying time, slow drug dissolution, and decrease the absorption rate.
11
Convection and diffusion of the drug molecules to the absorbing surface
Absorption of the drug across cell membranes into the systemic circulation
c. Th e rate-limiting step in the bioavailability of a drug from a drug product is the slowest step
in a series of kinetic processes.
For most conventional solid drug products (e.g., capsules, tablets), the dissolution rate is
the slowest, or rate-limiting, step for bioavailability.
For a controlled- or sustained-release drug product, the release of the drug from the
delivery system is the rate-limiting step.
2. Solutions:
Solutions are homogeneous mixtures of one or more solutes dispersed molecularly in a dissolving
medium (solvent).
Compared with other oral and peroral drug formulations, a drug dissolved in an aqueous
solution is in the most bioavailable and consistent form. Because the drug is already in
solution, no dissolution step is necessary before systemic absorption occurs. Peroral drug
solutions are often used as reference preparation for solid peroral formulations.
A drug dissolved in a hydroalcoholic solution (e.g., elixir) also has good bioavailability.
Alcohol aids drug solubility. However, when the drug is diluted by gastrointestinal tract
fluid and other gut contents (e.g., food), it may form a finely divided precipitate in the
lumen of the gastrointestinal tract. Because of the extensive dispersion and large surface
area of such finely divided precipitates, redissolution and subsequent absorption occur
rapidly.
A viscous drug solution (e.g., syrup) may interfere with dilution and mix with
gastrointestinal tract content. The solution decreases the gastric emptying rate and the rate
of transfer of drug solution to the duodenal region, where absorption is most efficient.
3. Suspensions:
Suspensions are dispersions of finely divided solid particles of a drug in a liquid medium in which
the drug is not readily soluble. Th e liquid medium of a suspension comprises a saturated solution
of the drug in equilibrium with the solid drug.
The bioavailability of the drug from suspensions may be like that of a solution because the
finely divided particles are dispersed and provide a large surface area for rapid dissolution.
On the other hand, a slow dissolution rate decreases the absorption rate.
Suspending agents are often hydrophilic colloids (e.g., cellulose derivatives, acacia,
xanthan gum) added to suspensions to increase viscosity, inhibit agglomeration, and
decrease the rate at which particles settle. Highly viscous suspensions may prolong gastric
emptying time, slow drug dissolution, and decrease the absorption rate.
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
12
4. Capsules:
Capsules are solid dosage forms with hard or soft gelatin shells that contain drugs, usually admixed
with excipients. Coating the capsule shell or the drug particles within the capsule can affect
bioavailability.
Hard gelatin capsules are usually filled with a powder blend that contains the drug.
Typically, the powder blend is simpler and less compacted than the blend in a compressed
tablet. After ingestion, the gelatin softens, swells, and begins to dissolve in the
gastrointestinal tract. Encapsulated drugs are released rapidly and dispersed easily, and
bioavailability is good. Hard gelatin capsules are the preferred dosage form for early
clinical trials of new drugs.
Soft gelatin capsules may contain a nonaqueous solution, a powder, or a drug suspension.
The vehicle may be water miscible (e.g., PEG). Th e cardiac glycoside digoxin, dispersed
in a water-miscible vehicle (Lanoxicaps), has better bioavailability than a compressed
tablet formulation (Lanoxin). However, a soft gelatin capsule that contains the drug
12
4. Capsules:
Capsules are solid dosage forms with hard or soft gelatin shells that contain drugs, usually admixed
with excipients. Coating the capsule shell or the drug particles within the capsule can affect
bioavailability.
Hard gelatin capsules are usually filled with a powder blend that contains the drug.
Typically, the powder blend is simpler and less compacted than the blend in a compressed
tablet. After ingestion, the gelatin softens, swells, and begins to dissolve in the
gastrointestinal tract. Encapsulated drugs are released rapidly and dispersed easily, and
bioavailability is good. Hard gelatin capsules are the preferred dosage form for early
clinical trials of new drugs.
Soft gelatin capsules may contain a nonaqueous solution, a powder, or a drug suspension.
The vehicle may be water miscible (e.g., PEG). Th e cardiac glycoside digoxin, dispersed
in a water-miscible vehicle (Lanoxicaps), has better bioavailability than a compressed
tablet formulation (Lanoxin). However, a soft gelatin capsule that contains the drug
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
13
dissolved in a hydrophobic vehicle (e.g., vegetable oil) may have poorer bioavailability
than a compressed tablet formulation of the drug.
Aging and storage conditions can affect the moisture content of the gelatin component of
the capsule shell and the bioavailability of the drug.
At low moisture levels, the capsule shell becomes brittle and is easily ruptured.
At high moisture levels, the capsule shell becomes moist, soft, and distorted.
Moisture may be transferred to the capsule contents, particularly if the contents
are hygroscopic.
5. Compressed tablets:
Compressed tablets are solid dosage forms in which high pressure is used to compress a powder
blend or granulation that contains the drug and other ingredients, or excipients, into a solid mass.
a. Excipients:
These include diluents (fillers), binders, disintegrants, lubricants, glidants, surfactants, dye,
and flavoring agents, have the following properties:
They permit the efficient manufacture of compressed tablets.
They affect the physical and chemical characteristics of the drug.
They affect bioavailability.
The higher the ratio of excipient to active drug, the greater the likelihood that the
excipients affect bioavailability.
b. Examples of Excipients:
1. Disintegrants (e.g. starch, croscarmellose, sodium starch glycolate) vary in action,
depending on their concentration; the method by which they are mixed with the powder
formulation; and the degree of tablet compaction. Although tablet disintegration is usually
not a problem because it often occurs more rapidly than drug dissolution, it is necessary
for dissolution in immediate-release formulations. Inability to disintegrate may interfere
with bioavailability.
2. Lubricants are usually hydrophobic, water-insoluble substances such as stearic acid,
magnesium stearate, hydrogenated vegetable oil, and talc. They may reduce wetting of the
surface of the solid drug particles, slowing the dissolution and bioavailability rates of the
drug. “Water soluble lubricants, such as l-leucine, do not interfere with dissolution or
bioavailability”
3. Glidants (e.g., colloidal silicon dioxide) improve the flow properties of a dry powder blend
before it is compressed. Rather than posing a potential problem with bioavailability,
glidants may reduce tablet-to-tablet variability and improve product efficacy.
4. Surfactants enhance drug dissolution rates and bioavailability by reducing interfacial
tension at the boundary between solid drug and liquid and by improving the wettability
(contact) of solid drug particles by the solvent.
13
dissolved in a hydrophobic vehicle (e.g., vegetable oil) may have poorer bioavailability
than a compressed tablet formulation of the drug.
Aging and storage conditions can affect the moisture content of the gelatin component of
the capsule shell and the bioavailability of the drug.
At low moisture levels, the capsule shell becomes brittle and is easily ruptured.
At high moisture levels, the capsule shell becomes moist, soft, and distorted.
Moisture may be transferred to the capsule contents, particularly if the contents
are hygroscopic.
5. Compressed tablets:
Compressed tablets are solid dosage forms in which high pressure is used to compress a powder
blend or granulation that contains the drug and other ingredients, or excipients, into a solid mass.
a. Excipients:
These include diluents (fillers), binders, disintegrants, lubricants, glidants, surfactants, dye,
and flavoring agents, have the following properties:
They permit the efficient manufacture of compressed tablets.
They affect the physical and chemical characteristics of the drug.
They affect bioavailability.
The higher the ratio of excipient to active drug, the greater the likelihood that the
excipients affect bioavailability.
b. Examples of Excipients:
1. Disintegrants (e.g. starch, croscarmellose, sodium starch glycolate) vary in action,
depending on their concentration; the method by which they are mixed with the powder
formulation; and the degree of tablet compaction. Although tablet disintegration is usually
not a problem because it often occurs more rapidly than drug dissolution, it is necessary
for dissolution in immediate-release formulations. Inability to disintegrate may interfere
with bioavailability.
2. Lubricants are usually hydrophobic, water-insoluble substances such as stearic acid,
magnesium stearate, hydrogenated vegetable oil, and talc. They may reduce wetting of the
surface of the solid drug particles, slowing the dissolution and bioavailability rates of the
drug. “Water soluble lubricants, such as l-leucine, do not interfere with dissolution or
bioavailability”
3. Glidants (e.g., colloidal silicon dioxide) improve the flow properties of a dry powder blend
before it is compressed. Rather than posing a potential problem with bioavailability,
glidants may reduce tablet-to-tablet variability and improve product efficacy.
4. Surfactants enhance drug dissolution rates and bioavailability by reducing interfacial
tension at the boundary between solid drug and liquid and by improving the wettability
(contact) of solid drug particles by the solvent.
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
14
c. Coated Tablets
Coatings may be sugar, film, or enteric and serve to:
Protect from moisture, light, air
Mask taste/odor
Enhance appearance
Modify release profile
d. Enteric Coated Tablet:
In addition, enteric coatings minimize contact between the drug and the gastric region by resisting
dissolution or attrition and preventing contact between the underlying drug and the gastric contents
or gastric mucosa. Some enteric coatings minimize gastric contact because they are insoluble at
acidic pHs. Other coatings resist attrition and remain whole long enough for the tablet to leave the
gastric area.
By resisting dissolution or attrition, enteric coating may decrease bioavailability. Enteric coatings
are used to
Minimize irritation of the gastric mucosa by the drug
Prevent inactivation or degradation of the drug in the stomach
Delay the release of drug until the tablet reaches the small intestine, where conditions for
absorption may be optimal.
5. Modified-release dosage forms:
These are drug products that alter the rate or timing of drug release. Because modified-release
dosage forms are more complex than conventional immediate-release dosage forms, more
stringent quality control and bioavailability tests are required. Dose dumping or the abrupt,
uncontrolled release of a large amount of drug is a problem.
a. Extended-release dosage forms include controlled-release, sustained-action, and long-acting
drug delivery systems. These delivery systems allow at least a twofold reduction in dosing
frequency compared with conventional immediate-release formulations.
The extended, slow release of controlled-release drug products produces a relatively
flat, sustained plasma drug concentration that avoids toxicity (from high drug
concentrations) or lack of efficacy (from low drug concentrations).
Extended-release dosage forms provide an immediate (initial) release of the drug,
followed by a slower sustained release.
b. Delayed-release dosage forms release active drug at a time other than immediately after
administration at a desired site in the gastrointestinal tract. For example, an enteric- coated drug
product does not allow for dissolution in the acid environment of the stomach but, rather, in the
less acidic environment of the small intestine.
14
c. Coated Tablets
Coatings may be sugar, film, or enteric and serve to:
Protect from moisture, light, air
Mask taste/odor
Enhance appearance
Modify release profile
d. Enteric Coated Tablet:
In addition, enteric coatings minimize contact between the drug and the gastric region by resisting
dissolution or attrition and preventing contact between the underlying drug and the gastric contents
or gastric mucosa. Some enteric coatings minimize gastric contact because they are insoluble at
acidic pHs. Other coatings resist attrition and remain whole long enough for the tablet to leave the
gastric area.
By resisting dissolution or attrition, enteric coating may decrease bioavailability. Enteric coatings
are used to
Minimize irritation of the gastric mucosa by the drug
Prevent inactivation or degradation of the drug in the stomach
Delay the release of drug until the tablet reaches the small intestine, where conditions for
absorption may be optimal.
5. Modified-release dosage forms:
These are drug products that alter the rate or timing of drug release. Because modified-release
dosage forms are more complex than conventional immediate-release dosage forms, more
stringent quality control and bioavailability tests are required. Dose dumping or the abrupt,
uncontrolled release of a large amount of drug is a problem.
a. Extended-release dosage forms include controlled-release, sustained-action, and long-acting
drug delivery systems. These delivery systems allow at least a twofold reduction in dosing
frequency compared with conventional immediate-release formulations.
The extended, slow release of controlled-release drug products produces a relatively
flat, sustained plasma drug concentration that avoids toxicity (from high drug
concentrations) or lack of efficacy (from low drug concentrations).
Extended-release dosage forms provide an immediate (initial) release of the drug,
followed by a slower sustained release.
b. Delayed-release dosage forms release active drug at a time other than immediately after
administration at a desired site in the gastrointestinal tract. For example, an enteric- coated drug
product does not allow for dissolution in the acid environment of the stomach but, rather, in the
less acidic environment of the small intestine.
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
15
7. Transdermal drug delivery systems, or patches:
These are controlled-release devices that contain the drug for systemic absorption after topical
application to the skin surface. Transdermal drug delivery systems are available for several drugs
(nitroglycerin, nicotine, scopolamine, clonidine, fentanyl, 17--estradiol, and testosterone).
Although the formulation matrices of these delivery systems differ somewhat, they all differ from
conventional topical formulations in the following ways:
They have an impermeable occlusive backing film that prevents insensible water loss from
the skin beneath the patch. This film causes increased hydration and skin temperature under
the patch and enhanced permeation of the skin by the drug.
The formulation matrix of the patch maintains the drug concentration gradient within the
device after application so that drug delivery to the interface between the patch and the
skin is sustained. As a result, drug partitioning and diffusion into the skin persist, and
systemic absorption is maintained throughout the dosing interval.
Transdermal drug delivery systems are kept in place on the skin surface by an adhesive
layer, ensuring drug contact with the skin and continued drug delivery.
8. Targeted (site-specific) drug delivery systems are drug carrier systems that place the drug
at or near the receptor site.
Examples include macromolecular drug carriers (protein drug carriers), particulate drug delivery
systems (e.g., liposomes, nanoparticles), and monoclonal antibodies. With targeted drug delivery,
the drug may be delivered to:
the capillary bed of the active site
a special type of cell (e.g., tumor cells) but not to the normal cells, and
a specific organ or tissue by complexing with a carrier that recognizes the target.
9. Inserts, Implants, and Devices
Used for localized or systemic controlled release.
Drug is embedded in biodegradable or nonbiodegradable matrices.
Inserted in cavities (vaginal, buccal) or tissues (subdermal).
Example: Leuprolide acetate implant (Viadur) for 1-year prostate cancer therapy.
Summary Table: Drug Delivery Systems and Key Characteristics
Dosage Form Physical State Key Mechanism
Rate-
Limiting
Step
Bioavailability
Key
Physicochemical
Factors
Examples
Solutions
Liquid (solute +
solvent)
Diffusion and
absorption
None
(already
dissolved)
Highest
Solubility,
stability
Aqueous
elixirs
Suspensions Solid in liquid Dissolution Dissolution
Moderate–
High
Particle size,
viscosity
Antacids,
antibiotics
15
7. Transdermal drug delivery systems, or patches:
These are controlled-release devices that contain the drug for systemic absorption after topical
application to the skin surface. Transdermal drug delivery systems are available for several drugs
(nitroglycerin, nicotine, scopolamine, clonidine, fentanyl, 17--estradiol, and testosterone).
Although the formulation matrices of these delivery systems differ somewhat, they all differ from
conventional topical formulations in the following ways:
They have an impermeable occlusive backing film that prevents insensible water loss from
the skin beneath the patch. This film causes increased hydration and skin temperature under
the patch and enhanced permeation of the skin by the drug.
The formulation matrix of the patch maintains the drug concentration gradient within the
device after application so that drug delivery to the interface between the patch and the
skin is sustained. As a result, drug partitioning and diffusion into the skin persist, and
systemic absorption is maintained throughout the dosing interval.
Transdermal drug delivery systems are kept in place on the skin surface by an adhesive
layer, ensuring drug contact with the skin and continued drug delivery.
8. Targeted (site-specific) drug delivery systems are drug carrier systems that place the drug
at or near the receptor site.
Examples include macromolecular drug carriers (protein drug carriers), particulate drug delivery
systems (e.g., liposomes, nanoparticles), and monoclonal antibodies. With targeted drug delivery,
the drug may be delivered to:
the capillary bed of the active site
a special type of cell (e.g., tumor cells) but not to the normal cells, and
a specific organ or tissue by complexing with a carrier that recognizes the target.
9. Inserts, Implants, and Devices
Used for localized or systemic controlled release.
Drug is embedded in biodegradable or nonbiodegradable matrices.
Inserted in cavities (vaginal, buccal) or tissues (subdermal).
Example: Leuprolide acetate implant (Viadur) for 1-year prostate cancer therapy.
Summary Table: Drug Delivery Systems and Key Characteristics
Dosage Form Physical State Key Mechanism
Rate-
Limiting
Step
Bioavailability
Key
Physicochemical
Factors
Examples
Solutions
Liquid (solute +
solvent)
Diffusion and
absorption
None
(already
dissolved)
Highest
Solubility,
stability
Aqueous
elixirs
Suspensions Solid in liquid Dissolution Dissolution
Moderate–
High
Particle size,
viscosity
Antacids,
antibiotics
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
16
Dosage Form Physical State Key Mechanism
Rate-
Limiting
Step
Bioavailability
Key
Physicochemical
Factors
Examples
Capsules (Hard) Solid
Dissolution post-
shell breakdown
Dissolution Good
Moisture,
excipient mix
Antibiotics,
vitamins
Capsules (Soft) Semisolid
Diffusion/release
from vehicle
Release
from
matrix
Variable Vehicle polarity
Digoxin
(Lanoxicaps)
Tablets Solid
Disintegration →
dissolution
Dissolution Variable
Compression
force, excipients
Aspirin,
acetaminophen
Enteric-Coated
Tablets
Solid
Dissolution in
intestine
Coating
dissolution
Delayed pH stability Omeprazole
Extended-
Release
Solid
Controlled
diffusion
Release
from
matrix
Sustained
Polymer
permeability
Propranolol
LA
Transdermal
Systems
Patch
Diffusion across
skin
Skin
barrier
Controlled
Lipophilicity,
MW
Nitroglycerin,
estradiol
Targeted
Systems
Nanoparticulate
Receptor-
mediated uptake
Transport
to site
Specific
Surface charge,
ligand affinity
Liposomal
doxorubicin
Implants/Inserts Solid (matrix)
Controlled
diffusion or
degradation
Matrix
erosion
Sustained
Polymer
composition
Leuprolide
(Viadur)
5. Regulatory and Practical Foundations
5.1 Dissolution Testing
In the 1960s, dissolution testing was introduced as an in vitro method to predict vivo absorption.
This became a regulatory cornerstone, required for quality control and batch-to-batch consistency.
5.2 In Vitro–In Vivo Correlation (IVIVC)
In the 1970s–1990s, IVIVC emerged as a tool linking dissolution profiles to plasma concentration–
time curves, enabling better formulation prediction and reducing the need for extensive human
studies.
5.3 Biopharmaceutics Classification System (BCS)
In 1995, Gordon Amidon and colleagues proposed the BCS, classifying drugs based on solubility
and permeability. The FDA adopted this framework in 2000, allowing biowaivers for certain drugs,
thereby institutionalizing biopharmaceutics in drug regulation.
6. Stories that Shaped Biopharmaceutics
6.1 Digoxin Brand Variability
Digoxin became infamous for brand-to-brand variability. Dissolution differences translated into
changes in clinical efficacy and toxicity, driving the FDA to tighten regulations and enforce
bioequivalence testing.
16
Dosage Form Physical State Key Mechanism
Rate-
Limiting
Step
Bioavailability
Key
Physicochemical
Factors
Examples
Capsules (Hard) Solid
Dissolution post-
shell breakdown
Dissolution Good
Moisture,
excipient mix
Antibiotics,
vitamins
Capsules (Soft) Semisolid
Diffusion/release
from vehicle
Release
from
matrix
Variable Vehicle polarity
Digoxin
(Lanoxicaps)
Tablets Solid
Disintegration →
dissolution
Dissolution Variable
Compression
force, excipients
Aspirin,
acetaminophen
Enteric-Coated
Tablets
Solid
Dissolution in
intestine
Coating
dissolution
Delayed pH stability Omeprazole
Extended-
Release
Solid
Controlled
diffusion
Release
from
matrix
Sustained
Polymer
permeability
Propranolol
LA
Transdermal
Systems
Patch
Diffusion across
skin
Skin
barrier
Controlled
Lipophilicity,
MW
Nitroglycerin,
estradiol
Targeted
Systems
Nanoparticulate
Receptor-
mediated uptake
Transport
to site
Specific
Surface charge,
ligand affinity
Liposomal
doxorubicin
Implants/Inserts Solid (matrix)
Controlled
diffusion or
degradation
Matrix
erosion
Sustained
Polymer
composition
Leuprolide
(Viadur)
5. Regulatory and Practical Foundations
5.1 Dissolution Testing
In the 1960s, dissolution testing was introduced as an in vitro method to predict vivo absorption.
This became a regulatory cornerstone, required for quality control and batch-to-batch consistency.
5.2 In Vitro–In Vivo Correlation (IVIVC)
In the 1970s–1990s, IVIVC emerged as a tool linking dissolution profiles to plasma concentration–
time curves, enabling better formulation prediction and reducing the need for extensive human
studies.
5.3 Biopharmaceutics Classification System (BCS)
In 1995, Gordon Amidon and colleagues proposed the BCS, classifying drugs based on solubility
and permeability. The FDA adopted this framework in 2000, allowing biowaivers for certain drugs,
thereby institutionalizing biopharmaceutics in drug regulation.
6. Stories that Shaped Biopharmaceutics
6.1 Digoxin Brand Variability
Digoxin became infamous for brand-to-brand variability. Dissolution differences translated into
changes in clinical efficacy and toxicity, driving the FDA to tighten regulations and enforce
bioequivalence testing.
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
17
6.2 Cyclosporine Reformulation
The development of cyclosporine microemulsion formulations showed how dramatic
improvements in bioavailability could be achieved by manipulating biopharmaceutic properties.
6.3 Generic Drug Expansion
As generic markets expanded, the need to demonstrate bioequivalence (a biopharmaceutic
principle) became critical, further reinforcing the discipline’s regulatory importance.
7. The Modern Role of Biopharmaceutics
7.1 Integration with Pharmacokinetics
Today, biopharmaceutics and pharmacokinetics are interwoven, especially through physiologically
based pharmacokinetic (PBPK) modeling, which uses solubility, dissolution, and permeability data
to predict systemic exposure.
7.2 Clinical Relevance
Biopharmaceutics now underpins:
Quality control testing (dissolution, disintegration).
Generic drug approval (bioequivalence).
Early drug development (formulation optimization).
Regulatory decision-making (biowaivers, BCS, IVIVC).
8. Applications of Biopharmaceutics
Since its inception, biopharmaceutics has grown into a highly applied science, serving as a
foundation for both drug development and clinical practice. Its applications can be categorized
into classical, modern, and futuristic realms.
Classical Applications
1. Bioavailability and Bioequivalence Studies
Early in the 1960s and 70s, researchers and regulators noticed that patients responded
differently to supposedly “identical” formulations of drugs such as digoxin and
theophylline. This variability gave rise to the concepts of bioavailability (the rate and extent
to which a drug reaches systemic circulation) and bioequivalence (when two products show
comparable bioavailability under similar conditions). These studies became the
cornerstone of generic drug approval worldwide. Today, regulatory agencies like the FDA,
EMA, and WHO still rely heavily on these studies to ensure patient safety and therapeutic
interchangeability.
2. Dosage Form Design
17
6.2 Cyclosporine Reformulation
The development of cyclosporine microemulsion formulations showed how dramatic
improvements in bioavailability could be achieved by manipulating biopharmaceutic properties.
6.3 Generic Drug Expansion
As generic markets expanded, the need to demonstrate bioequivalence (a biopharmaceutic
principle) became critical, further reinforcing the discipline’s regulatory importance.
7. The Modern Role of Biopharmaceutics
7.1 Integration with Pharmacokinetics
Today, biopharmaceutics and pharmacokinetics are interwoven, especially through physiologically
based pharmacokinetic (PBPK) modeling, which uses solubility, dissolution, and permeability data
to predict systemic exposure.
7.2 Clinical Relevance
Biopharmaceutics now underpins:
Quality control testing (dissolution, disintegration).
Generic drug approval (bioequivalence).
Early drug development (formulation optimization).
Regulatory decision-making (biowaivers, BCS, IVIVC).
8. Applications of Biopharmaceutics
Since its inception, biopharmaceutics has grown into a highly applied science, serving as a
foundation for both drug development and clinical practice. Its applications can be categorized
into classical, modern, and futuristic realms.
Classical Applications
1. Bioavailability and Bioequivalence Studies
Early in the 1960s and 70s, researchers and regulators noticed that patients responded
differently to supposedly “identical” formulations of drugs such as digoxin and
theophylline. This variability gave rise to the concepts of bioavailability (the rate and extent
to which a drug reaches systemic circulation) and bioequivalence (when two products show
comparable bioavailability under similar conditions). These studies became the
cornerstone of generic drug approval worldwide. Today, regulatory agencies like the FDA,
EMA, and WHO still rely heavily on these studies to ensure patient safety and therapeutic
interchangeability.
2. Dosage Form Design
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
18
Controlled-release tablets, enteric-coated formulations, and soft-gel capsules were classical
applications of biopharmaceutic knowledge. By studying dissolution rates, gastric pH, and
intestinal transit, scientists could modify drug release patterns. For example, enteric-coated
aspirin protects the stomach lining while ensuring absorption in the intestine.
3. Drug–Food Interactions
Classical studies revealed how food could alter drug absorption. For example, tetracyclines
chelate with calcium in milk, drastically reducing their bioavailability. Similarly, high-fat
meals can delay gastric emptying and thus delay drug absorption. Such findings still inform
drug labeling and dosing recommendations today.
Modern Applications
1. Biopharmaceutics Classification System (BCS)
Introduced by Amidon et al. in the 1990s, BCS categorizes drugs into four classes based
on solubility and intestinal permeability. This classification revolutionized regulatory
sciences by determining when biowaivers (exemption from in vivo studies) could be
granted. For example, highly soluble and highly permeable drugs (Class I) often do not
require extensive bioequivalence trials.
2. Biopharmaceutics Drug Disposition Classification System (BDDCS)
A refinement of BCS, BDDCS also considers drug metabolism. Proposed by Benet and
colleagues, it helps predict not only absorption but also how a drug will be eliminated
(hepatic metabolism vs. renal excretion). This system guides early drug discovery,
formulation design, and even drug–drug interaction studies.
3. In Vitro–In Vivo Correlation (IVIVC):
To reduce animal and human testing, IVIVC models were developed to predict human
absorption from laboratory dissolution profiles. Regulatory authorities now encourage
IVIVC as a tool to accelerate formulation development, optimize release profiles, and
support biowaivers.
4. Patient-Centric Formulation
Modern biopharmaceutics ensures dosage forms are tailored to special populations: orally
disintegrating tablets (ODTs) for children, liquid suspensions for pediatrics, and easy-to-
swallow gels or dissolving films for geriatrics. The focus is shifting from one-size-fits-all
to patient convenience and compliance.
5. Targeted and Controlled Drug Delivery
Biopharmaceutics underpins the engineering of nanoparticles, liposomes, microspheres,
and polymeric implants. These systems control absorption rates, bypass biological barriers,
and enable targeted therapy—such as liposomal doxorubicin for cancer, which reduces
systemic toxicity.
6. Physiologically Based Pharmacokinetic (PBPK) Modeling
18
Controlled-release tablets, enteric-coated formulations, and soft-gel capsules were classical
applications of biopharmaceutic knowledge. By studying dissolution rates, gastric pH, and
intestinal transit, scientists could modify drug release patterns. For example, enteric-coated
aspirin protects the stomach lining while ensuring absorption in the intestine.
3. Drug–Food Interactions
Classical studies revealed how food could alter drug absorption. For example, tetracyclines
chelate with calcium in milk, drastically reducing their bioavailability. Similarly, high-fat
meals can delay gastric emptying and thus delay drug absorption. Such findings still inform
drug labeling and dosing recommendations today.
Modern Applications
1. Biopharmaceutics Classification System (BCS)
Introduced by Amidon et al. in the 1990s, BCS categorizes drugs into four classes based
on solubility and intestinal permeability. This classification revolutionized regulatory
sciences by determining when biowaivers (exemption from in vivo studies) could be
granted. For example, highly soluble and highly permeable drugs (Class I) often do not
require extensive bioequivalence trials.
2. Biopharmaceutics Drug Disposition Classification System (BDDCS)
A refinement of BCS, BDDCS also considers drug metabolism. Proposed by Benet and
colleagues, it helps predict not only absorption but also how a drug will be eliminated
(hepatic metabolism vs. renal excretion). This system guides early drug discovery,
formulation design, and even drug–drug interaction studies.
3. In Vitro–In Vivo Correlation (IVIVC):
To reduce animal and human testing, IVIVC models were developed to predict human
absorption from laboratory dissolution profiles. Regulatory authorities now encourage
IVIVC as a tool to accelerate formulation development, optimize release profiles, and
support biowaivers.
4. Patient-Centric Formulation
Modern biopharmaceutics ensures dosage forms are tailored to special populations: orally
disintegrating tablets (ODTs) for children, liquid suspensions for pediatrics, and easy-to-
swallow gels or dissolving films for geriatrics. The focus is shifting from one-size-fits-all
to patient convenience and compliance.
5. Targeted and Controlled Drug Delivery
Biopharmaceutics underpins the engineering of nanoparticles, liposomes, microspheres,
and polymeric implants. These systems control absorption rates, bypass biological barriers,
and enable targeted therapy—such as liposomal doxorubicin for cancer, which reduces
systemic toxicity.
6. Physiologically Based Pharmacokinetic (PBPK) Modeling
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
19
PBPK models integrate anatomical, physiological, and biochemical parameters into a
mathematical framework that simulates drug absorption, distribution, metabolism, and
excretion across organs. They allow prediction of drug behavior in children, pregnant
women, renal/hepatic impairment, and even different ethnic populations, often before
clinical trials. Regulators like FDA and EMA now accept PBPK as part of submissions for
dosage adjustments and drug–drug interaction assessments.
Future Realm of Biopharmaceutics
1. Personalized Biopharmaceutics
Future formulations will not only consider general physiology but also individual
variations in genetics, microbiome composition, and disease state. For example,
polymorphisms in drug transporters (like P-glycoprotein) may influence absorption, while
gut microbiota may metabolize drugs differently. Personalized formulations (via genomic
and microbiome profiling) could optimize therapeutic outcomes.
2. Organs-on-Chips and In Silico Biopharmaceutics
o Organs-on-Chips: Microfluidic devices mimicking the human intestine, liver, and
kidney can replicate absorption and metabolism more accurately than animal
models. For example, gut-on-chip models simulate peristalsis and mucus secretion,
making drug absorption studies more realistic.
o In Silico Software: Advanced computational tools (e.g., GastroPlus, Simcyp, PK-
Sim) integrate dissolution, permeability, and physiological data to simulate
absorption and predict pharmacokinetics in humans. These are now standard tools
in pharma R&D.
3. Artificial Intelligence (AI) in Drug Absorption Prediction
AI and machine learning models are being trained on massive datasets of drug solubility,
permeability, dissolution, and PK profiles to design optimized formulations. This allows
prediction of how a new molecule will behave in the body, minimizing trial-and-error in
development.
4. 3D Printing of Medicines
3D printing enables the creation of tablets with complex geometries, layered drug release
profiles, and individualized doses. In 2015, the FDA approved Spritam® (levetiracetam),
the first 3D-printed drug for epilepsy, manufactured by Aprecia Pharmaceuticals using
ZipDose® technology. This breakthrough demonstrated that 3D printing can produce
highly porous tablets that disintegrate rapidly, improving patient compliance. Future
directions include on-demand printing in hospitals and pharmacies, tailored to individual
patients.
5. Biologics and Advanced Therapies
19
PBPK models integrate anatomical, physiological, and biochemical parameters into a
mathematical framework that simulates drug absorption, distribution, metabolism, and
excretion across organs. They allow prediction of drug behavior in children, pregnant
women, renal/hepatic impairment, and even different ethnic populations, often before
clinical trials. Regulators like FDA and EMA now accept PBPK as part of submissions for
dosage adjustments and drug–drug interaction assessments.
Future Realm of Biopharmaceutics
1. Personalized Biopharmaceutics
Future formulations will not only consider general physiology but also individual
variations in genetics, microbiome composition, and disease state. For example,
polymorphisms in drug transporters (like P-glycoprotein) may influence absorption, while
gut microbiota may metabolize drugs differently. Personalized formulations (via genomic
and microbiome profiling) could optimize therapeutic outcomes.
2. Organs-on-Chips and In Silico Biopharmaceutics
o Organs-on-Chips: Microfluidic devices mimicking the human intestine, liver, and
kidney can replicate absorption and metabolism more accurately than animal
models. For example, gut-on-chip models simulate peristalsis and mucus secretion,
making drug absorption studies more realistic.
o In Silico Software: Advanced computational tools (e.g., GastroPlus, Simcyp, PK-
Sim) integrate dissolution, permeability, and physiological data to simulate
absorption and predict pharmacokinetics in humans. These are now standard tools
in pharma R&D.
3. Artificial Intelligence (AI) in Drug Absorption Prediction
AI and machine learning models are being trained on massive datasets of drug solubility,
permeability, dissolution, and PK profiles to design optimized formulations. This allows
prediction of how a new molecule will behave in the body, minimizing trial-and-error in
development.
4. 3D Printing of Medicines
3D printing enables the creation of tablets with complex geometries, layered drug release
profiles, and individualized doses. In 2015, the FDA approved Spritam® (levetiracetam),
the first 3D-printed drug for epilepsy, manufactured by Aprecia Pharmaceuticals using
ZipDose® technology. This breakthrough demonstrated that 3D printing can produce
highly porous tablets that disintegrate rapidly, improving patient compliance. Future
directions include on-demand printing in hospitals and pharmacies, tailored to individual
patients.
5. Biologics and Advanced Therapies
Biopharmaceutics Lecture 1 Baasir Umair Khattak (Mphill in pharmacology, QAU)
20
Biopharmaceutic principles are now being applied to monoclonal antibodies, peptides,
nucleic acids (RNA/DNA drugs), and gene therapies. These molecules face unique
challenges (e.g., enzymatic degradation, poor permeability), requiring novel delivery
systems like lipid nanoparticles (as used in mRNA COVID-19 vaccines).
6. Space Biopharmaceutics
Space exploration introduces unique biopharmaceutic challenges:
o Microgravity alters gastrointestinal motility, gastric emptying, and fluid
distribution, all of which influence drug absorption.
o Cosmic radiation may destabilize certain drugs during long missions.
Current research by NASA and ESA is exploring how PK/PD models must be
adapted to microgravity and how drug formulations can be stabilized for deep-space
travel. Space biopharmaceutics is not science fiction anymore—it is a growing
research area for ensuring astronaut health on missions to Mars and beyond.
9. Conclusion
Biopharmaceutics arose not as an academic curiosity but as a scientific and clinical necessity.
Gerhard Levy’s vision to recognize the dosage form as a determinant of therapeutic response
reshaped pharmaceutical sciences. While pharmacokinetics quantifies drug behavior in the body,
biopharmaceutics explains how the drug becomes available in the first place. Together, they form
complementary pillars of modern pharmacology and pharmaceutics.
References (select, foundational)
1. Teorell T. Kinetics of distribution of substances administered to the body. Arch Int
Pharmacodyn Ther. 1937.
2. Dost FH. Der Blutspiegel: Kinetik der Konzentrationsabläufe in der Körperflüssigkeit.
1953.
3. Levy G. (1960s). University at Buffalo courses and publications introducing
biopharmaceutics.
4. Wagner JG. History of Pharmacokinetics. Pharmacol Ther. 1981.
5. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic
drug classification. Pharm Res. 1995.
6. FDA. Guidance for Industry: Waiver of In Vivo Bioavailability and Bioequivalence Studies
for Immediate-Release Solid Oral Dosage Forms Based on BCS. 2000.
20
Biopharmaceutic principles are now being applied to monoclonal antibodies, peptides,
nucleic acids (RNA/DNA drugs), and gene therapies. These molecules face unique
challenges (e.g., enzymatic degradation, poor permeability), requiring novel delivery
systems like lipid nanoparticles (as used in mRNA COVID-19 vaccines).
6. Space Biopharmaceutics
Space exploration introduces unique biopharmaceutic challenges:
o Microgravity alters gastrointestinal motility, gastric emptying, and fluid
distribution, all of which influence drug absorption.
o Cosmic radiation may destabilize certain drugs during long missions.
Current research by NASA and ESA is exploring how PK/PD models must be
adapted to microgravity and how drug formulations can be stabilized for deep-space
travel. Space biopharmaceutics is not science fiction anymore—it is a growing
research area for ensuring astronaut health on missions to Mars and beyond.
9. Conclusion
Biopharmaceutics arose not as an academic curiosity but as a scientific and clinical necessity.
Gerhard Levy’s vision to recognize the dosage form as a determinant of therapeutic response
reshaped pharmaceutical sciences. While pharmacokinetics quantifies drug behavior in the body,
biopharmaceutics explains how the drug becomes available in the first place. Together, they form
complementary pillars of modern pharmacology and pharmaceutics.
References (select, foundational)
1. Teorell T. Kinetics of distribution of substances administered to the body. Arch Int
Pharmacodyn Ther. 1937.
2. Dost FH. Der Blutspiegel: Kinetik der Konzentrationsabläufe in der Körperflüssigkeit.
1953.
3. Levy G. (1960s). University at Buffalo courses and publications introducing
biopharmaceutics.
4. Wagner JG. History of Pharmacokinetics. Pharmacol Ther. 1981.
5. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic
drug classification. Pharm Res. 1995.
6. FDA. Guidance for Industry: Waiver of In Vivo Bioavailability and Bioequivalence Studies
for Immediate-Release Solid Oral Dosage Forms Based on BCS. 2000.
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