5. Pharmaceutical solutions.pdf

Pharmacy ppt nice note

1. 04-Jan-19 1
Pharmaceutical Solutions

S

IPPP A4KGETMES

2. Outline
Introduction
General methods of preparation
Formulation of solutions (API and Excipients)
Excipients
Solutions taken orally
Solutions used in the mouth and throat
Solutions instilled into body cavities

04-Jan-19 2 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

3. Objectives
After completing this chapter, you will be able to:

Define pharmaceutical solutions

Describe Methods of preparation of pharmaceutical
solutions

Understand advantages and limitations of solution dosage
forms

Describe use of excipients in pharmaceutical solutions

Describe the different types of pharmaceutical solutions
04-Jan-19 3 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

4. Introduction
Pharmaceutical solutions are homogeneous liquid preparations
containing one or more drugs and appropriate excipients dissolved
in a suitable solvent or mixture of solvents.

The solvent could be aqueous or non – aqueous


Employed solvent mixtures should be mutually miscible system

Based on the route of administration sol
n
s can be classified as:

Oral solutions: such as Syrups, elixirs, drops


Sol
n
s for mouth and throat: such as Mouth washes, gargles.....


Sol
n
s for body cavities: such as Rectal (douches, enemas), Otic (ear
drops), nasal drops/sprays, Ophthalmic (eye drops)....


Sol
n
s for Injection : such as Injectable


Topical Sol
n
s: such as Collodions, lotions....


04-Jan-19 IPPP A4KGETMES 4 MU, CHS, SOP, Department of Pharmaceutics

5. Based on the type of the solvent/ solvent system used, solutions
can be classified as:

Aqueous solutions include simple solutions, syrups, aromatic
waters and dry powder mixtures for reconstitution.

Nonaqueous solutions may include hydro-alcoholic solutions, such
as mouthwashes, gargles, elixirs, and oily preparations (e.g., oil-
soluble vitamins).

Based on the need for sterility, solutions can be classified as:

Sterile solutions such as injectable, ophthalmic, otic solutions ....

Non sterile solutions: such as oral and topical solutions


04-Jan-19 5 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

6. Methods of preparation
1.Simple Solutions:
In this method,ƒ sol
n
s are prepared by dissolving the required
amount of drug/s in a solvent/s, mixing until dissolved, then
adding sufficient solvent to bring the sol
n
to the final volume

The solvent may contain other ingredients that stabilize or
solubilize the API.

Most pharmaceutical sol
n
s are prepared by this method i.e. by
simple mixing of the drug/s with the solvent/s

On an industrial scale, sol
n
s are prepared in large mixing vessels
with mechanical stirrers
Thermostatically controlled mixing tanks may be used when heat
is desired.
04-Jan-19 IPPP A4KGETMES 6 MU, CHS, SOP, Department of Pharmaceutics

7. 2. Solution by chemical reaction:
Solutions are prepared by reacting two or more solutes with
each other in a suitable solvent.
Eg. 1. Aluminum sub-acetate topical solution USP: which is
topically applied for certain eczematous skin conditions as
astringent wash or wet dressing







Eg. 2. Magnesium Citrate oral solution: which is used as
saline cathartic prepared by reacting magnesium carbonate with
Citric acid.






04-Jan-19 7 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

8. 3. Solution by extraction:

Drugs or pharmaceuticals of vegetable or animal origin often
are prepared using suitable extraction process with the help of
solvent/s.

Extracts of such type which contains the desired constituents
from crude materials using solvents in which the desired
constituents are soluble can be termed as solutions.

Most commonly known as extractives.

04-Jan-19 IPPP A4KGETMES 8 MU, CHS, SOP, Department of Pharmaceutics

9. Advantages of Solutions

The drug is immediately available for absorption
Hence greater bioavailability from the GIT

Flexible dosing is possible

Solutions may be designed for any route of administration
Oral, Parenteral (injections), rectal (enemas), topical and
ophthalmic preparations

The drug is uniformly distributed throughout the preparation
Uniform dose can be measured at any given time hence there is no
need to shake the container

They facilitate swallowing in difficult cases.
e.g. infants or the elderly or any case of dysphagia

Reduced irritation to the gastric mucosa, compared to solid
dosage forms, due to immediate dilution by gastric contents.


04-Jan-19 IPPP A4KGETMES 9 MU, CHS, SOP, Department of Pharmaceutics

10. Limitations of solutions

Unsuitable for chemically unstable drugs in the presence of
water and poorly soluble drugs.
Although there are methods of enhancing stability and solubility

Even if a drug is some what stable, its stability is often reduced
in solution by solvolysis, hydrolysis or oxidation

Hence, commonly solutions have a shorter expiry

It is difficult to mask unpleasant tastes.

Need flavoring, but this will not always be successful

Solutions are bulky, difficult and expensive to transport and
prone to breakages

Technical accuracy is needed to measure the dose on administration.

Hence a measuring device should be provided for administration
04-Jan-19 IPPP A4KGETMES 10 MU, CHS, SOP, Department of Pharmaceutics

11. Stability of solutions

Drug substances are generally more susceptible to degradation
in liquids than in solid dosage forms.

In addition to the stability of the drug in solution, the stability
of the excipients such as colorants, flavors, preservatives,
solubilizers, and sweeteners should also be considered.

As a class of formulations, oral liquids are more complex in
composition than parenterals, hence more interactions may
occur affecting the stability of this product.

Hence stability of a given formulation could be due to any
physical change or chemical process

In this case chemical and physical stability should be considered
04-Jan-19 IPPP A4KGETMES 11 MU, CHS, SOP, Department of Pharmaceutics

12. Chemical instability reactions includes -hydrolysis, oxidation,
isomerization, and epimerization.

Interactions b/n ingredients and with container closure
materials are established as the principal causes of these
reactions. Some examples of chemical instability are

The hydrolysis of cefotaxime sodium,
The oxidation of vitamin C,
Physical instability of liquid formulations involves the formation
of precipitates, less-soluble polymorphs, adsorption to
container surfaces, microbial growth and changes in product
appearance.
Product acceptability is interlinked with their appearance
which includes properties such as color, odor, taste, and clarity.

04-Jan-19 12 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

13. Excipients used in pharmaceutical solutions
The main constituent of pharmaceutical solutions could be:
The active drug (API)
Solvents (vehicle)
Co-solvents
Buffers
Preservatives
Antioxidants
Flavorants ......

04-Jan-19 13
Formulating agents (Excipients)
N.B: Not all formulating agents should
present in a given formulation
Excipients are pharmacologically inert compounds that are
included in the formulation to:
Enhance the solubility of the API
Enhance the stability (physical and chemical) of the formulation
Facilitate the administration of the dosage form, such as pourability,
palatability

IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

14. A.Vehicle (Solvent)
A vehicle is the medium that contains all the ingredients of a
formulation. In case of solns it can be called the solvent.

The choice depends on the intended use of the formulation and the
physicochemical property of the API/s and excipients

Water is commonly used solvent b/c it is relatively cheap,
tasteless, non-irritant and non-toxic

However, Tap/drinking water should not be used b/c of chemical
incompatibilities within formulations

The most common and preferred solvent in the preparation of
aqueous pharmaceutical solns, except parenterals (injections), is
Purified Water

It has fewer solid impurities i.e. when evaporated to dryness, must
not yield > 0.001% of residue

PW can be prepared by distillation, ion exchange methods or
reverse osmosis.
04-Jan-19 14 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

15. 04-Jan-19 15 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

16. B. Co-solvents:
Cosolvents are water miscible organic solvents used to increase
the solubility of the therapeutic agent within the formulation.

They are also used to enhance the solubility of volatile constituents

The main co-solvents used in pharmaceutical solution
formulations includes:

1.Alcohol (CH
3CH
2OH)
Ethyl alcohol (ethanol) (94.9 - 96.0% v/v) had previously been
the most commonly used solvent in oral preparations because

its excellent solvent properties for many non-polar drugs

its favorable taste.

pharmacological and toxicological effects compromised the use
of alcohol in pharmaceutical preparations. – pediatric formulation
04-Jan-19 IPPP A4KGETMES 16 MU, CHS, SOP, Department of Pharmaceutics

17. 2.Glycerol (also termed glycerin)
Odorless, sweet liquid that is miscible with water having similar
co-solvency properties to ethanol.
3.Propylene Glycol
Odorless, colorless, viscous liquid diol generally used as a
replacement for glycerin
4.Poly (ethylene glycol) (PEG)
It’s a polymer composed of repeating units of the Ethylene oxide
monomer units whose physical state depends on the number of this
monomers (i.e the Mwt.)
Macrogols 200, 300, 400- viscous liquid
Macrogols 1500- greasy semisolid
Macrogols 1540, 3000, 4000, 6000 - waxy solids

Lower-molecular-weight grades (PEG 200, PEG 400) are preferred
as co-solvents in pharmaceutical solutions


04-Jan-19 IPPP A4KGETMES 17 MU, CHS, SOP, Department of Pharmaceutics

18. C. Buffers
The solubility and stability (e.g., hydrolysis and oxidation) of
most available drugs are pH-dependent

Hence, changes in pH could compromise the solubility and
stability of different drug formulations

Buffer solutions are employed to control the pH of the
solutions/ formulated product at a specific range.

Thus, pH control is performed to:

1.Enhance the stability of products in which the chemical
stability of the active agent is pH-dependent

2.Maintain the solubility of the therapeutic agent in the
formulated product.

pH range of a formulation/drug should then be optimized so as
to obtain better physicochemical performance and stability.



04-Jan-19 18 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

19. Examples of buffer salts used in pharmaceutical solutions
include:
Acetates (acetic acid and sodium acetate):
Citrates (citric acid and sodium citrate):
Phosphates (sodium phosphate and disodium phosphate):

04-Jan-19 19 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

20. D. Preservatives
Solutions, specially the oral preparations, are the most likely
formulations to be contaminated by microorganisms:

This risk is more enhanced by the fact that
most of these preparations are marketed in a multi-dose form.
Sugars/other excipients enriches growth-supporting substrates.
manufacturing process contribute microbiological contamination.
Many natural origin raw materials may contain viable spores

Hence preservatives are included in pharmaceutical solutions to
prevent microbial growth or to reduce/limit the microbial
bioburden of the formulation.

04-Jan-19 20 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

21. 04-Jan-19 21
Ideally, preservatives should be
Non toxicity, compatible, soluble, acceptable (taste & odour)

Broad spectrum antimicrobial activity encompassing Gram-
positive and negative bacteria and fungi

Stable (physicochemical & microbiologically) over the shelf-life


However no single preservative exists that satisfy all the ideal
requirements for all formulation.

Frequently, a combination of two or more preservatives are
employed to enhance antimicrobial spectrum and effect.

A wide range of preservatives are available, however, their
selection must be made based on microbiological studies

They are classified as acidic neutral mercurial and quaternary
ammonium compounds (4
O
AC).



IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

22. Acidic preservatives: are the most widely used preservatives in oral
preparations having adequately aqueous solubility

They possess both antifungal and antibacterial properties and includes
Benzoic acid and its salts (0.1–0.3%)
Alkyl esters of parahydroxybenzoic acid (alkyl-parabens) (0.001–0.2%),
Sorbic acid and its salts (0.05–0.2%)...

The other classes have been widely used in ophthalmic, nasal, and
parenteral products, but not frequently in oral liquid preparations.

Neutral preservatives: are volatile alcohols and their volatility introduces
problems of odor and loss of preservative on aging in multi-dose
preparations.

Mercurial and 4
O
AC are excellent preservatives but are subject to
incompatibilities
Mercurials reduced in to free mercury
4
O
AC s are inactivated by anionic substances
04-Jan-19 22 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

23. The activity of a preservative depends on the presence of the
correct form (unionized) at the required concentration (the
minimum inhibitory concentration MIC) in the formulation.
Hence any factor that affect the form and/or the concentration
affects the activity of the preservative

1.the pH of the formulation
2.the presence of micelles
3.the presence of hydrophilic polymers
e.g. polyvinylpyrrolidone, methylcellulose
04-Jan-19 23 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

24. 04-Jan-19 24 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

25. E. Antioxidants
Antioxidants are cpds that enhance the stability of drugs that are
susceptible to oxidative degradation.

Many drugs in solution are subject to oxidative degradation
which can be accompanied by change in color, odor, or drug
precipitation.

Oxidation is a loss of electron/s by a molecule/cpd or element
that changes its oxidation state.

Often it involves the addition of electronegative atoms (as
Oxygen, halogens (F, Cl, Br...)) or the removal of Hydrogen.

Such reactions are mediated by free radicals or molecular
oxygen, and are often catalyzed by metal ions.
04-Jan-19 25 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

26. Mechanism of action of antioxidants
Having higher oxidative potential: hence they are oxidized in
preference to the therapeutic agent, thereby protecting the drug
from decomposition
Inhibit free radical-induced oxidative chain reaction:



Antioxidants may also be used in combination with chelating
agents which can form complexes with heavy-metal
ionscatalyze oxidative degradations
Ethylenediamine tetraacetic acid (EDTA),
Citric acid


04-Jan-19 26 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

27. 04-Jan-19 27
Both water-soluble and water-insoluble antioxidants are
commercially available,
the choice made depends on the nature of the formulation.

Aqueous soluble antioxidants:
Sodium metabisulphite((Na
2S
2O
5 ) (0.01 – 0.1%)
Sodium sulphite (0.1%), Sodium bisulphite (NaHSO
3)
Sodium formaldehyde sulphoxylate
Ascorbic acid

Oil-soluble antioxidants include:
Butylated hydroxyanisole (BHA), (0.005 – 0.02%)
Butylated hydroxytoluene (BHT), (0.007 – 0.1%)
ethyl, propyl or dodecyl gallate, ( 1%)

IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

28. F. Sweetening agents
Sweeteners are components of many liquid oral dosage forms,
especially those containing bitter or other unacceptable tastes.

Used to increase the palatability of the therapeutic agent.

Sweeteners can be classified as
nutritive (caloric) and non-nutritive (non-caloric) or
natural and synthetic

Some of the most commonly used sweeteners include sucrose,
sorbitol, mannitol, liquid glucose, honey, molasses, saccharin,
aspartame, sucralose....

The use of sugars in oral formulations for children and patients
with diabetes mellitus is to be avoided.



04-Jan-19 IPPP A4KGETMES 28 MU, CHS, SOP, Department of Pharmaceutics

29. Sucrose is the most widely used nutritive natural sweetener
with a long history of use.
It is a white crystalline powder soluble in water and alcohol.
Chemically and physically stable in the pH range of 4.0–8.0.
It has higher tendency to crystallize ......‘‘cap-locking’’

Saccharin is a non-nutritive synthetic sweetening agent that is
about 500 times sweeter than sucrose.
It had unpleasant bitter or matalic aftertaste, however, its Na salt
form is more palatable and comparatively free of aftertaste

Aspartame is 200 times sweeter than sucrose and, unlike
saccharin, has no aftertaste.
It is stable in the solid form, but its stability in solution is
temperature and pH dependent.

Sucralose is about 600 times sweeter than sucrose and it is
heat stable and stable over a wide range of pH
04-Jan-19 IPPP A4KGETMES 29 MU, CHS, SOP, Department of Pharmaceutics

30. G. Flavorants
Unfortunately the vast majority of drugs in solution are
unpalatable, and therefore, the addition of flavors is often
required to mask the taste of the drug substance.

Taste-masking using flavors is a difficult task; however, there
are some empirical approaches that may be taken to produce a
palatable formulation.

Usually a combination of flavours is used to achieve the optimal
taste-masking property.

Addition of certain excipients called flavour adjuncts (e.g.
menthol, chloroform) to augment the taste-masking properties of
conventional flavors by


add flavor to the formulation

 desensitize the taste receptors

04-Jan-19 IPPP A4KGETMES 30 MU, CHS, SOP, Department of Pharmaceutics

31. This is particularly useful in pediatric formulation to ensure
patient compliance.

Flavors that may be used to mask

04-Jan-19 IPPP A4KGETMES 31
Salty taste Bitter taste Sweet taste Sour taste
Butterscotch cherry Vanilla fruit citrus flavours
Apricot mint berry raspberry
Peach anise
Vanilla
wintergreen
mint MU, CHS, SOP, Department of Pharmaceutics

32. H.Colorants:
The use of colorants in medicinal products affords no direct
therapeutic benefit,

the psychological effects have long been recognized.

any patients rely on color to recognize the prescribed drug and
proper dosage

When used in combination with flavours, the selected colour
should ‘match’ the flavour of the formulation,

green with mint- flavoured solutions,

red for strawberry- flavoured solutions

The colorant must be soluble, nonreactive with other
components, stable at the pH range and under the intensity of
light that the solution is likely to encounter during its shelf life
04-Jan-19 IPPP A4KGETMES 32 MU, CHS, SOP, Department of Pharmaceutics

33. I. Viscosity-enhancing agents
Controlling the viscosity of the formulation
Ensure the accurate measurement of the volume to be dispensed
Increase the palatability (with increase in viscosity)

Certain liquid formulations do not require the specific addition
of viscosity-enhancing agents (e.g. syrups) due to their
inherent viscosity.
Commonly used viscosity imparting agents in pharmaceutical
solutions are :
Non-ionic (neutral) polymers
•Cellulose derivatives, e.g. Methylcellulose, Hydroxyethylcellulose
hydroxypropylcellulose
•Polyvinylpyrrolidone
Ionic polymers sodium carboxymethylcellulose (anionic)
sodium alginate (anionic).

04-Jan-19 33 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

34. I. Pharmaceutical solutions for oral administration


There are three principal types of solution formulations that are
administered orally:
Oral solutions
Oral syrups and
Oral elixirs.

04-Jan-19 IPPP A4KGETMES 34 MU, CHS, SOP, Department of Pharmaceutics

35. 1.Oral Solutions
Oral solutions are administered to the gastrointestinal tract to
provide systemic absorption of the therapeutic agent

Due to the resilience of the gastrointestinal environment, oral
solutions may be formulated over a broad pH range.
However, unless there is an issues of solubility /stability of the
drug, the usual pH of oral solutions is approximately 7.0

Typically the following classes of excipients are used in the
formulation of oral solutions:
buffers (e.g. citrate, phosphate)
preservatives (e.g. parabens, benzoic acid, sorbic acid)
water-soluble antioxidants (e.g. sodium metabisulphite)
flavours and colours
viscosity-modifying agents hydrophilic polymers are used, e.g.
sodium alginate, hydroxyethylcellulose


04-Jan-19 IPPP A4KGETMES 35 MU, CHS, SOP, Department of Pharmaceutics

36. Oral rehydration solutions are usually effective in treatment of
patients with mild volume depletion.

Rapid fluid loss can lead to dehydration accompanied by
depletion of sodium, potassium, and bicarbonate ions.

Oral rehydration solutions are used for fluid and electrolyte
replacement

Dry mixtures for solution are prepared for a number of
medicinal agents which have insufficient stability in aqueous
solution to meet extended shelf-life periods.

The powder contains all of the components, including drug,
flavorants, colorant, buffers and others, except for the solvent.

Once reconstituted, the solution remains stable usually 7 to
14 days when stored as indicated, then has to be discarded


04-Jan-19 IPPP A4KGETMES 36 MU, CHS, SOP, Department of Pharmaceutics

37. 2. Syrups
Syrups are concentrated aqueous viscous solution of a sugar or
sugar substitute with /without flavoring agents and medicinal
substances.

Traditional/Simple syrup is mainly composed of purified water
and sucrose in a solution, concentration about 60 -85%.
This doesn’t contain medicaments or flavors

Due to the presence of high concentration of sucrose simple
syrups does not require the following excipients

Sweetening agents

Viscosity-modifying agents

Preservatives



04-Jan-19 IPPP A4KGETMES 37 MU, CHS, SOP, Department of Pharmaceutics

38. Flavored/non-medicated syrups are also available which
contains flavoring agents but not medicinal substances
intended to serve as pleasant means of administering a
disagreeable tasting drug particularly effective in youngsters

Examples of flavored syrups include cherry syrup, cocoa
syrup, orange syrup, raspberry syrup....

Choice of syrup vehicle must be made with due consideration
to the physicochemical properties of the therapeutic agent.

For instance cherry syrup and orange syrup have acidic nature
Should not be used with acid drugs
Chemical stability for acid-labile therapeutic agents.



04-Jan-19 IPPP A4KGETMES 38 MU, CHS, SOP, Department of Pharmaceutics

39. Most medicated syrups contain the following components

Medicinal agent/s

Purified water

Sugar, usually sucrose, or sugar substitute

Preservatives, Flavorants and Colorants

Sometimes, small amount of alcohol is added to dissolve alcohol-
soluble ingredients such as a poorly water-soluble flavorants

Sucrose is most frequently used sugar in syrups which can be
replaced in whole or in part by other substances:

Such as Sorbitol, glycerin, and propylene glycol

All glycogenic substances (materials converted to glucose in the
body), can be replaced by non-glycogenic substances

Hence the resulting will be Sugar free syrups
04-Jan-19 IPPP A4KGETMES 39 MU, CHS, SOP, Department of Pharmaceutics

40. Sugar-free syrups
Recently, many products have been formulated as medicated
sugar-free syrups due to the glycogenetic and cariogenic
properties of sucrose.

This are aimed for diabetic patients and children

Sugar free syrups are not that different from the other syrups in
composition, the only possible difference could be the use of

Artificial sweeteners

•Saccharin sodium, Aspartame ...

Non-glycogenetic viscosity modifiers

•methylcellulose, hydroxyethylcellulose...
04-Jan-19 IPPP A4KGETMES 40 MU, CHS, SOP, Department of Pharmaceutics

41. Preparation of Syrups
Syrups are most frequently prepared by one of the ff.
methods, depending on the physical and chemical
characteristics of the ingredients.

a.Solution of the ingredients with the aid of heat

b.Solution of the ingredients with the of agitation or the simple
admixture of liquid components,
04-Jan-19 IPPP A4KGETMES 41 MU, CHS, SOP, Department of Pharmaceutics

42. a. Solution with the Aid of Heat
This method of syrup preparation is employed when

the components are not thermolabile or volatile and

Quick preparation of syrup is desired

Sugar is added to the purified water, and heat is applied until
the sugar is dissolved

Then, other heat-stable components are added to the hot syrup,
the mixture is allowed to cool

Heat-labile agents or volatile substances, such as volatile
flavoring oils and alcohol, are added and

Its volume is adjusted to the proper level by the addition of
purified water.
04-Jan-19 IPPP A4KGETMES 42 MU, CHS, SOP, Department of Pharmaceutics

43. Conducting syrup preparation at higher temperature will result in
inversion, a chemical conversion of sucrose into its components
(glucose and fructose).

due to fructose, the resulting syrup is sweeter than the original
and dark in color

the presence of acids enhances this process



However if excessively heated, the sweet taste will be destroyed
and a dark brown liquid is formed, a process known as
caramelization.

Syrups so decomposed are more susceptible to fermentation and
to microbial growth than the orginal syrups
04-Jan-19 43
inverted sugar
IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

44. b. Solution by Agitation
This is employed to avoid heat-induced inversion of sucrose

This process is more time consuming than the use of heat, but the
product has maximum stability.

On a small scale, sucrose and other agents may be dissolved in
purified water by permitting thorough agitation of the mixture

Huge glass lined or stainless steel tanks with mechanical stirrers
or agitators are employed in large-scale preparation of syrups

When solid agents are to be added to a syrup, it is best if
dissolved in small amount of purified water as solid substances
dissolve slowly because

Viscosity of syrups does not permit readily distribution of the solid
limited amount of available water is present in concentrated syrups


04-Jan-19 44 IPPP A4KGETMES MU, CHS, SOP, Department of Pharmaceutics

45. 3. Oral Elixirs
Elixirs are clear, sweetened hydroalcoholic solutions intended for
oral use and are usually flavored to enhance their palatability.

Non-aqueous solvents (alcohol, glycerin or propylene glycol)
form a significant proportion of the vehicle used in elixirs

Hence their concentration is sufficient to ensure that the
components of the formulation remain in solution.

Non-medicated elixirs are employed as vehicles, and medicated
elixirs are used for the therapeutic effect of the medicinal
substances they contain.

The presence of alcohol in elixirs presents a possible problem in
pediatric formulations and, indeed, for those adults who wish to
avoid alcohol.


04-Jan-19 IPPP A4KGETMES 45 MU, CHS, SOP, Department of Pharmaceutics

46. The following excipients are the most common in elixirs

Purified water and Alcohol (Generally >10% v/v as a co-solvent)

Co-solvents: may be used to enhance the solubility of the
components, Polyols e.g. propylene glycol, glycerol

Sweetening agents: syrup, sorbitol solution and artificial
sweeteners

Flavors and colorants: enhance palatability and the aesthetic
qualities of the formulation.

viscosity-enhancing agents: e.g. hydrophilic polymers, may be
required to optimize viscosity

 Elixirs containing more than 10% to 12% of alcohol are usually
self-preserving and do not require the addition of an antimicrobial
agent
04-Jan-19 IPPP A4KGETMES 46 MU, CHS, SOP, Department of Pharmaceutics

47. Preparation of Elixirs
Elixirs are usually prepared by simple solution with agitation
and/or by admixture of two or more liquid ingredients.

First, Alcohol-soluble and water-soluble components are
dissolved separately in alcohol and purified water respectively.

Then the aqueous solution is added to the alcoholic solution,
rather than the reverse, to maintain the highest possible
alcoholic strength at all times so that minimal separation of the
alcohol-soluble components occurs.

Eventually when the two solutions are completely mixed, the
mixture is made to the volume with the specified solvent
04-Jan-19 IPPP A4KGETMES 47 MU, CHS, SOP, Department of Pharmaceutics

48. Eg. Phenobarbitone elixir: anticonvulsant
Phenobarbitone---------------0.4g
Ethanol(90%)-------------------40ml Cosolvent
Compound orange spirit-----2.5ml Flavor
Glycerol---------------------------40ml Cosolvent
Amaranth solution------------1ml Colorant (deep
purple)
Purified water to--------------1000ml Vehicle/solvent

Dissolve Phenobarbitone in Ethanol(90%), add orange spirit. Add
Glycerol, then Amaranth. Make volume with water.
04-Jan-19 IPPP A4KGETMES 48 MU, CHS, SOP, Department of Pharmaceutics

49. Compared with syrups, elixirs are :
Usually contain a lower proportion of sugar hence

less sweet, less viscous and less effective in taste masking

Better to maintain both water- soluble and alcohol-soluble
components in solution b/c of their hydroalcoholic character,

Preferred to syrups from a manufacturing stand-point

b/c of their stable characteristics and ease of preparation (simple
solution)

Because of their usual content of volatile oils and alcohol,
elixirs should be stored in tight, light-resistant containers and
protected from excessive heat.



04-Jan-19 IPPP A4KGETMES 49 MU, CHS, SOP, Department of Pharmaceutics

50. Linctuses
Linctuses are viscous, liquid oral preparations that are usually
prescribed for the relief of cough.
chiefly used for a demulcent, expectorant or sedative purpose,
principally in the treatment of cough.

They usually contain a high proportion of syrup and glycerol
which have a demulcent effect on the membranes of the throat

intended to be sipped slowly and swallowed slowly, allowed
to trickle down the throat in an undiluted form.
04-Jan-19 IPPP A4KGETMES 50
Other oral solutions MU, CHS, SOP, Department of Pharmaceutics

51. E.g. Simple linctus
Citric acid, Chl.spirit and
Conc. Anice water=>
Flavorants
Syrup= demulcent




Dissolve citric acid in chl.spirit, Conc. Anice water & amaranth
soln. and Add syrup to volume


04-Jan-19 IPPP A4KGETMES 51 MU, CHS, SOP, Department of Pharmaceutics

52. Aromatic waters:
Are aqueous solutions saturated with volatile oil or other volatile
substances
Use: Internal: as flavoring agent, as preservative, for medical purpose
Examples:
Chloroform water (flavorant in preparations)
Chloroform --------2.5ml
Water FBC to---------1000ml
Double strength Chloroform water (preservative, flavorant)
Chloroform --------5ml
Water FBC to---------1000ml
Peppermint water (carminative)
Peppermint oil------0.2ml
Water FBC to---------100ml
External: as perfumes
eg. Rose water
04-Jan-19 IPPP A4KGETMES 52 MU, CHS, SOP, Department of Pharmaceutics

53. Spirits/essences:
Spirits are alcoholic or hydroalcoholic solutions of volatile
substances.
Mainly used as flavoring agents, some are used internally for medical
purpose
most of them are prepared by simple solution in alcohol
Examples:
Peppermint spirit BP 88: Carminative, flavorant
Peppermint oil----------------100ml
Ethanol(90%) to---------------1000ml
Chloroform spirit: flavoring agent, preservative
Chloroform------------50ml
Ethanol(90%) to------1000ml
04-Jan-19 IPPP A4KGETMES 53 MU, CHS, SOP, Department of Pharmaceutics

54. Tinctures:
Tinctures are alcoholic or hydroalcoholic solutions prepared from
vegetable materials or from chemical substances.

When prepared from chemical substances (e.g., iodine,
thimerosal), they are prepared by simple solution of the agent
in the solvent

Benzoin tincture, is prepared by maceration of the natural
components in the solvent

Tinctures contain alcohol approx. 15% to 80%.

The alcohol content protects against microbial growth and
keeps the alcohol-soluble extractives in solution.
04-Jan-19 IPPP A4KGETMES 54 MU, CHS, SOP, Department of Pharmaceutics

55. 04-Jan-19 IPPP A4KGETMES 55
Because of alcohol content, tinctures must be tightly stoppered
and not exposed to excessive temperatures.

Because many of the constituents found in tinctures undergo a
photochemical change upon exposure to light, many tinctures
must be stored in light-resistant containers and protected from
sunlight MU, CHS, SOP, Department of Pharmaceutics

56. II. Solutions used in the mouth and throat

Gargles and mouthwashes
Aqueous solutions that are intended for treatment of the throat
(gargles) and mouth (mouthwashes) and are generally
formulated in a concentrated form.

These preparations must be diluted before use and care should
be taken to ensure that appropriate instructions are included on
the label and that the container used will be easily
distinguishable from those containing preparations intended to
be swallowed.

04-Jan-19 IPPP A4KGETMES 56 MU, CHS, SOP, Department of Pharmaceutics

57. Eg. Compound sodium chloride mouthwash














04-Jan-19 IPPP A4KGETMES 57
Mitt. 50ml
“diluted with an equal volume of warm
water”
NaCl: has anti-edema effect
NaHCO3: commonly used as a pH buffering agent, an electrolyte replenisher,
alkalizer MU, CHS, SOP, Department of Pharmaceutics

58. III. Solutions instilled into body cavities
Enemas and douches

These are preparations often formulated as solutions (though
they may be presented as an emulsion or suspension) and are
intended for instillation into the

rectum (enema) or

other orifice, such as the vagina or nasal cavity (douche).

The volumes of these preparations may vary from 5mL to much
larger volumes.

When the larger volumes are used it is important that the liquid
is warmed to body temperature before administration.
04-Jan-19 IPPP A4KGETMES 58 MU, CHS, SOP, Department of Pharmaceutics

59. RETENTION ENEMAS: are solutions administered rectally for their
local effects or systemic absorption. E.g.
Hydrocortisone enema for local effect

Aminophylline enema for systemic absorption

aminophylline, rectal administration minimizes the undesirable
GI reactions associated with oral therapy.

EVACUATION ENEMAS: are solutions used to cleanse the bowel.

Commercially, many enemas are available in disposable plastic
squeeze bottles containing a premeasured amount of enema
solution.

The agents are solutions of sodium phosphate and sodium
biphosphate, glycerin and docusate potassium, and light
mineral oil.
04-Jan-19 IPPP A4KGETMES 59 MU, CHS, SOP, Department of Pharmaceutics

60. Douches are used for their hygienic effects, few douche
powders containing specific therapeutic anti infective agents

Powders (packaged in bulk or as unit packages) are used to
prepare solutions for vaginal douche, i.e., for irrigation
cleansing of the vagina

The bulk powders are used by the teaspoonful or table-
spoonful in preparation of the desired solution

The user simply adds the prescribed amount of powder to the
appropriate volume of warm water and stirs until dissolved
04-Jan-19 IPPP A4KGETMES 60 MU, CHS, SOP, Department of Pharmaceutics

61. Solution preparations intended for injection

Injections are sterile, pyrogen free, that is, bacterial endotoxin
free, preparations intended to be administered parenterally.



04-Jan-19 IPPP A4KGETMES 61 MU, CHS, SOP, Department of Pharmaceutics

62. Types of parenteral solutions
Injection: are liquid preparations that are drug substances or
solutions.
e.g., Insulin Injection, USP

If the drug is insoluble in water, an injection may be prepared
as an aqueous suspension or as a solution in a suitable
nonaqueous solvent.

Powder for injection: If a drug is unstable in solution, it may
be prepared as a dry powder intended for reconstitution with
a proper solvent at the time of administration

e.g. Cefuroxime for injection, USP

Ampiccilin sodium for injection, usp
04-Jan-19 IPPP A4KGETMES 62 MU, CHS, SOP, Department of Pharmaceutics

63. Excipients used in Parenteral Solutions
Solvents and vehicles
water for injection, USP:
most frequently used solvent in the large scale manufacturer
of injections

It is purified by distillation or reverse osmosis process

It meets the same standards for the presence of total solids
as does Purified Water, USP
i.e., not more than 1 mg/100 mL water for injection, USP

is not required to be sterile, but it must be pyrogen free.

used in the manufacture of injectable products to be
sterilized after preparation
04-Jan-19 IPPP A4KGETMES 63 MU, CHS, SOP, Department of Pharmaceutics

64. Sterile water for injection, USP:
As with water for injection, sterile water for injection must be
pyrogen free

not more than 0.25 USP endotoxin units per milliliter.

It is intended to be used as a solvent, vehicle, or diluent for
already sterilized and packaged injectable medications.

they are used for reconstitution of multiple antibiotics.

the water is aseptically added to the vial of medication to
prepare the desired injection.
04-Jan-19 IPPP A4KGETMES 64 MU, CHS, SOP, Department of Pharmaceutics

65. Bacteriostatic water for injection, USP,

It is sterile water for injection containing one or more suitable
antimicrobial agents.

 It is packaged in pre-filled syringes or in vials containing not
more than 30mL of the water.

 The container label must state the names and proportions of
the antimicrobial agent or agents.

employed as a sterile vehicle in the preparation of small
volumes of injectable preparations.

label state not for use in neonates, because of the toxicity of
the bacteriostat, benzyl alcohol.
04-Jan-19 IPPP A4KGETMES 65 MU, CHS, SOP, Department of Pharmaceutics

66. Ringer’s injection, USP,
is a sterile solution of sodium chloride, potassium chloride,
and calcium chloride in water for injection.
The three agents are present in concentrations similar to
those of physiologic fluids.
Ringer’s is employed as a vehicle for other drugs or alone as
an electrolyte replenisher and plasma volume expander.
Lactated Ringer’s Injection, USP
it contains sodium lactate
This injection is a fluid and electrolyte replenisher
04-Jan-19 IPPP A4KGETMES 66 MU, CHS, SOP, Department of Pharmaceutics

67. NONAQUEOUS VEHICLES
Used when limited water solubility of a medicinal
substance or its susceptibility to hydrolysis is an issue

Among the nonaqueous solvents employed in parenteral
products are

 fixed vegetable oils,
glycerin, polyethylene glycols, propylene glycol, alcohol,
 less often used agents, including ethyl oleate, isopropyl myristate,
and dimethyl acetamide

04-Jan-19 IPPP A4KGETMES 67 MU, CHS, SOP, Department of Pharmaceutics

68. Antibacterial preservatives; Agents containing cationic
surface active cpds (0.01%)

Agents such as chlorobutanol, cresol, and phenol (0.5%)

Antioxidants Sulfur dioxide as an antioxidant or for an
equivalent amount of the sulfite, bisulfite, or metabisulfite of
potassium or sodium (0.2%)

Buffers,, and other adjuncts may be included as required

However, Agents employed solely for their coloring and
flavoring effect are strictly prohibited in parenteral products


04-Jan-19 IPPP A4KGETMES 68 MU, CHS, SOP, Department of Pharmaceutics