A brief introduction to pharmaceutics first undergraduate pharmacy students

A brief introduction to pharmaceutics first undergraduate pharmacy students

1. Introduction to dosage forms Dr. Jacqueline Njeri Muchiri MPS Dpharm , Bpharm , MScPhar , PDGME

2. INTRODUCTION TO DOSAGE FORMS This course unit gives you the basics of pharmaceutics. COURSE OUTLINE Definition of terms Dosage forms Pharmaceutical formulations Scope of pharmaceutics Drug development Pre-formulation

3. Definition of key terms Pharmacy-is the art and science of preparation and usage of drugs. Pharmacy is the link between health sciences with chemical sciences and aims to ensure safe and effective use of pharmaceuticals. Pharmacist- a healthcare professional qualified to prepare and dispense drugs. Myth “a pharmacists is a person who counts tablets and tells you how to take them”- Disarm this myth in ≤100 words ( to be submitted two weeks before CATs)

4. Pharmaceutics is: The science of dosage form design That discipline of pharmacy that deals with all aspects of turning a new chemical entity (NCE) into a stable, safe, and effective medicinal preparation ready for use by the patient. A multi-disciplinary area, encompassing and utilizing knowledge of chemistry, physics, biology, anatomy, physiology, biochemistry, microbiology, economics e.t.c ., to design dosage forms with optimal delivery performance

5. The process of achieving a suitable dosage form with the desirable properties is a complex one that requires multiple scientific, medical, legal, commercial and regulatory expertise.

6. Drug : a chemical substance which when administered to a living organism results in a physiological/ biological effect in the body. This effect can be negative or positive. Example Heroin Drugs can be consumed via inhalation, injection, smoking, ingestion, absorption or dissolution under the tongue. Medicine : aka Pharmaceutical drug, is a drug with benefits to the body, that is to say- a product produced and regulated to impart a positive medical effect on a patient used for diagnosis, prevention and or cure.

7. Differences between drug and medicine Drug Substance with effect to body API mostly crude No suitable dose or dosage form. May or may not be useful May be non selective Medicine Substance with positive effect (benefit) to the body API formulated with excipients- modified drug Suitable dosage form and dose Always useful selective

8. Both drugs and medicines can be poisons- true or false? All medicines are drugs- true or false? All drugs are medicines- true or false? Give examples of drugs that are not medicine

9. Effect - pharmacological change caused by a drug. Can be desired/intended/predicted or the opposite E fficacy - It is the ability to produce a desired amount of the desired effect, or success in achieving a given goal in the most economical way. Effectiveness - is often more specifically used in the context of how well something accomplishes a task. E ffectiveness is well measured in real world setting while efficacy in ideal conditions (clinical trials)

10. Demonstration Patient A has headache, takes paracetamol J® 500mg, after 30 minutes headache is clear + nausea Patient B has headache, takes paracetamol D® 500mg, after 15 minutes headache is clear Identify: Effect Effectiveness

11. Possible effects: Therapeutic effect " desired and intended changes in the body Side effects of drugs are the effects which we do not want to have , but are no deleterious, Adverse effect: Any response to drug that is noxious and unintended and that occurs at doses used in main for drug purpose Toxic effects mean noxious effects induced by over dosage of drugs or accumulation of large amount of drugs

12. Placebo effects- psychological and physiological responses that occur after taking an inactive substance- influenced by the patients belief Allergic reactions- not universal, After effect/ withdrawal: The effect still exists, after withdrawal of the drug, the drug concentration is below the threshold, such as, the patient feels hangover next morning, after taking barbiturates. Secondary effects : After long term of using broad spectrum antibiotics, due to the change of intestinal normal flora opportunistic fungal infection can occur Addictive effects- some drugs cause physical and psychological dependence

13. Dose - is the predetermined amount of the drug administered at one time to produce a certain degree of biological response in a patient Dosage - is the prescribed administration of a predetermined amount, number, and frequency of doses of drug over a specific period of time Dosage form- is the physical form in which a precise mixture of API and excipients are presented to help easy administration, deliver to sites of action, achieve rapid onset of action, and improve bioavailability etc.

14. Demonstration: Rx Caps Amoxycillin 500mg TID 7/7 Tabs Paracetamol 1000mg TID PRN Identify the: Dosage form Dose Dosage

15. Drug design is the process of creating new medications, or improving existing ones, to treat diseases and improve human health. It involves identifying a target molecule within the body that plays a role in the disease process, and then designing a drug that can interact with this target in a specific way to produce a therapeutic effect.

16. Active pharmaceutical ingredient (API) Biologically active component of a drug that produces the desired effects Specific molecule responsible for treating medical condition

17. Excipients : are the inert components in the formulation of a dosage form, other than the API. (An excipient in a drug product may be an API in another drug, depending on the intended use, e.g. sucrose, ascorbic acid). They are added to the formulation for a specific purpose and have well defined functions in a drug product, such as vehicles, binders, disintegrants, lubricants, etc. Synonymous with adjunct, additive and manufacturing aid .

18. Bioavailability : fraction of administered drug that reaches circulation unchanged and becomes available to its intended biological destination. For effectiveness, The active substance needs to be available in the correct dose at the specific site in the body where it has to work. This specific site is referred to as the ‘target site’. Also, the active substance needs to reach the target site within a certain time, and be available there for a defined time.

19. Bioequivalence Bioequivalence means that the identical active pharmaceutical ingredient of two medicines have the same rate and extent of absorption . The medicines produce the same effect at the required target. Bioequivalence is often used to compare an original and generic version of a medicine, or two different formulations (for instance, tablet or oral suspension) of the same medicine.

20. Blood drug levels : actual concentration of drug present in plasma. Usually zero at administration, increases with absorption and decreases with elimination. For IV it is 100% at administration Pharmacological toxicity - Drug toxicity can occur as a result of the over-ingestion of medication, causing too much of the drug to be in a person's system at once

21. LECTURE 11

22. W hen do you say that something is stable? Drug Stability? The term drug stability refers to the extent to which a drug substance or product retains, within specified limits and throughout its period of storage and use, the same properties and characteristics that it possessed at the time of its manufacture factors that affect this stability include temperature, light, pH, oxidation and enzymatic degradation chemical, physical and therapeutic stability during handling and storage

23. Shelf life- the period between manufacture and expiry of a product. Safety: Drug safety is the main aspect of medical therapy that can play a major role in deciding which drug should be given to a patient A ccurate dosage and formulation released or absorbed without causing adverse effects to the patient

24. Sterilization : Refers to any process that removes, kills, or deactivates all forms of life (particularly microorganisms such as fungi , bacteria , spores , and unicellular eukaryotic organisms) and other biological agents such as prions present in or on a specific surface, object, or fluid. Sterilization can be achieved through various means, including heat , chemicals , irradiation , high pressure , and filtration After sterilization, an object is referred to as being sterile or aseptic .

25. Disinfection - disinfection is the process of eliminating or reducing harmful microorganisms from inanimate objects and surfaces Contamination- the process of making something dirty or poisonous, or the state of containing unwanted or dangerous substances I ntroction of unwanted materials Cross contamination- this is contamination of a raw material, intermediate product of finished product with another material during the process of production.

26. QA Quality assurance can be defined as "part of quality management that provides evidence and establishes confidence that quality requirements will be/ have been fulfilled." The confidence provided by quality assurance is twofold—internally to management and externally to customers, government agencies, regulators, certifiers, and third parties.

27. An alternate definition is "all the planned and systematic activities implemented within the quality system that can be demonstrated to provide confidence that a product or service will fulfill requirements for quality." Why QA? To ensure the delivery of quality products to clients Help to exercise regulatory functions Provide evidence Provide confidence

28. QC Quality control : a part of quality management focused on fulfilling  quality requirements by initiating and coordinating: Quality development (detect and prevent defects) Quality maintenance Quality improvement Economical production Customer satisfaction Quality control is more the inspection aspect of quality management. An alternate definition is "the operational techniques and activities used to fulfill requirements for quality."

29. When to do QC When raw materials are received During the production process On finished products

30. Though the two are similar, but there are some basic differences. Quality control is concerned with examining the product or service — the end result ‐ and quality assurance is concerned with examining the process that leads to the end result. A company would use quality assurance to ensure that a product is manufactured in the right way, thereby reducing or eliminating potential problems with the quality of the final product.

31. QA (company based) QC (lab based) Strategies to prevent defects (QA) Strategies to detect defects (QC) Process oriented (QA) Product oriented (QC)

32. Good manufacturing processes: is a system that ensures proper design, monitoring and control of manufacturing processes and facilities. E nsures that products are consistently produced and controlled according to quality standards It is designed to minimize the risks involved in any pharmaceutical production that cannot be eliminated through testing the final product. cGMPs are enforced by the regulation agancy of the conutry.

33. Components of cGMP Personnel Plant environment/ layout Equipment Production process Documentation

34. ASSIGNMENT Pharmacopoeia Compendia Formulary For the above mentioned, do the following: Define Identify their differences Identify their similarities

35. References Pharmaceutics, By M. E. Aulton (International student edition) Remington, The Science and Practice of Pharmacy, 21 st Edition Pharmaceutical Dosage Forms, Howard A. Ansel Dispensing for Pharmaceutical Students, S. J. Carter The British Pharmaceutical Codex

36. LECTURE 3 SCOPE OF PHARMACEUTICS

37. BPH 2.1 TOPIC 2 SCOPE OF PHARMACEUTICS DR. J.N. MUCHIRI MPS. MSc Phar, PGDME, Bpharm , Dpharm

38. That discipline of pharmacy that deals with all aspects of turning a new chemical entity (NCE) into a stable, safe, efficacious and effective medicinal preparation ready for use by the patient.

39. Course outline Classifications of dosage forms Description of dosage forms Design and formulation of medicines Good dispensing procedures Manufacture of medicines (Small and large scale)

40. Dosage forms Dosage forms are made through combination of the API and excipients Various dosage forms of the same drug can be made through selective manipulation of the excipients e.g. dry starch acts as a disintegrant while wet starch is used as a binder Dosage forms must achieve a predictable therapeutic response and reproducible product quality

41. Product quality parameters Chemical, physical and biological compatibility of the API and excipients Preservation Dose uniformity Acceptable to users Suitable packaging Proper labeling Easy identification Affordability

42. Factors to consider when choosing a dosage form Biopharmaceutical factors – these are drug factors that affect pharmacokinetics e.g. solubility, pH, chemical structure Drug factors – physicochemical properties of the drug e.g. dissolution, solid state, interactions 3. Therapeutic factors Clinical indication- illness, duration of action Patient factors – age, organ function, patient state

43. Types of dosage forms Route of administration Dosage forms Oral Tablets, capsules, solutions, syrups, elixirs., powders, emulsions, gels, etc. Topical Creams, ointments, pastes, lotions, solution, gels, topical aerosols, dusting powders, suppositories, etc. Parenteral Injectable dosage forms (solutions, suspensions, emulsions), implants, irrigation and dialysis solutions), suppositories, etc. Pulmonary Aerosols (solutions, suspensions, emulsions, powder), inhalation vapors & gases, prays, etc. Rectal Suppositories, ointment, cream, powders, gels, solutions, etc. Nasal Inhalations, solutions, ointments, sprays, etc. Eye Solutions, ointments, creams, etc. Ear Solutions, suspensions, ointments, etc.

44. Classification under state of matter Solids Semi-solids liquids Gases New drug delivery sys Powder Ointments Syrup Aerosal Transdermal patches Tablets Creams Elixer inhalation Nano particles Capsules Suppository Suspension Radiopharmaceutical Catchets Pessary Emulsion Depot plaster gel lotion

45. The need for dosage form There is need to design a dosage form to achieve a predictable therapeutic outcome to a drug in the formulation capable of large scale manufacture with reproducible product quality . To achieve product quality : chemical and physical stability, preservation against microbial spoilage and contamination, uniformity of dose of drug, acceptability to users (prescriber and patient), suitable packaging and labelling.

46. 1-Accurate dose. 2-Protection e.g. coated tablets, sealed ampoules. 3-Protection from gastric juice. 4-Masking taste and odor (to make palatable). 5-Placement of drugs within body tissues. 6-Sustained release medication. 7-Controlled release medication. 8-Optimal drug action. 9-Insertion of drugs into body cavities (rectal, vaginal) 10-Use of desired vehicle for insoluble drug

47. Need for different dosage form of same drug To minimize discomfort and instant relief and improve patient compliance Desirable properties of dosage form: • Convenient to handle, use and store • Stable during storage and use • Withstand mechanical shock during transport • Flexibility in different drug strength • Provide expected therapeutic effect • Extent, drug release, onset, intensity, duration of action predictable • Economical and elegant

48. PHARMACEUTICAL FORMULATIONS

49. Pharmaceutical formulation is the multistep process where the active drug(API) is mixed with all other components(Excipients) to result in the final beneficial medicinal product. Factors to consider: particle size, polymorphism, pH, Solubility.

50. components for a successful pharmaceutical formulation: Benefits and constraints of the (APIs), Valuable excipients, Associated interactions, and Manufacturing procedure The dosage form is the pharmaceutical drug product as marketed for use with a specific mixture of active ingredients and inactive components. It has to be a particular configuration(capsule shell, for example) and distributed into a particular dose. 

51. SOLIDS AND SEMI SOLIDS

52. SOLID DOSAGE FORMS Tablets Are the most commonly used solid dosage forms A tablet is a unit solid dosage form of a compressed preparation containing: 5-10% API 10% disintegrating and dissolution agents 80% other excipients (fillers, glidants , lubricants, binders) Can be uncoated, or coated( film, sugar, enteric) Can be formulated as controlled release

53. Characteristic of ideal tablet Free from defects ( chips, cracks, discoloration, contamination, fragile) Chemical and physical stability; with other ingredients, packaging material Capable of releasing API in predictable manner Strong enough to withstand mechanical stress of production, packaging and transportation.

54. Excipients used in tablets: Diluents- fillers to make up bulk Lactose, starch, microcrystalline cellulose Binders and adhesives- promote granulation MCC, gelatin, molasses Disinter grants; facilitate disintegration Cellulose, cornstarch Lubricants; reduce friction between particles and particles and between particles and dies Talc, magnesium stearate

55. Anti adherence; reduce sticking to the die and punch Glidants ; reduce friction among particles and promotes flowability Colors and dyes; uniformity and elegance Aluminium lake colors Flavoring and sweetening agents; limited to chewable tablets

56. Types/ Classes of tablets Sublingual/ buccal tabs- dissolve rapidly and absorbed through the mucous membrane of the mouth Suitable for drugs that are destroyed by gastric juice or poorly absorbed in the GIT Eg : nitroglycerine tabs Lozenges- solid preparation containing sugar and gum, meant for sucking for local relief of throat irritation Dental cones- tablet form intended to be placed in the empty socket of an extracted tooth to prevent bacterial growth or pain Chewable tabs- disintegrate smoothly and rapidly when chewed. Mostly contain sweeteners and flavours Eg : multivitamins, antacids

57. Effervescent tabs- uncoated, contain acid substances and bicarbonates which react rapidly in the presence of water by releasing carbon dioxide Eg Alker -seltzer Routine compressed tabs; swallowed intact Layered tabs; prepared by compressing a tablet granulation around a previously compressed granulation. Coated tabs: Enteric coated/ delayed release Film coated Sugar coated

58. Advantages of tablets Precision and low content variability Low manufacturing cost Easy to package and ship Easy to swallow Easy to identify Special release forms Tamperproof Disadvantages of tablets Some resist compression Uncertain bioavailability Bad taste and odor can be very pronounced

59. Capsules Are solid dosage forms in which drug substance ( powder, oil, granulation) is enclosed within a gelatinous shell. Are intended to be swallowed whole. Hard gelatin capsules: Contain dry powders, solids Two phase shell Soft gelatin capsules: Contain liquids, oils, semisolids Continuous shell

60. Powders A mixture of finely divided drugs/ chemicals in a dry form used internally or externally. Advantages of powders Disadvantages of powders Flexibility of compounding Inaccuracy of dose Good chemical stability Unsuitable for hygroscopic drugs Rapid dispersion due to small particle size Pronounced bad taste

61. Semi solids Cream- emulsion of oil and water in approximately equal proportions that penetrates the stratum corneum Ointment- is a greasy, viscous preparation of oil and water in 4:1 ratio that forms an effective barrier against moisture loss Gel- are semisolid systems consisting of dispersions of small or large molecules in an aqueous liquid vehicle rendered jelly-like through the addition of a gelling agent. -liquifies upon contact with the skin

62. Paste- combines water, oil and powder and is extremely thick on application. Suppository-small solid or semisolid medicated mass usually cone shaped that is inserted into the rectum Pessary / vaginal suppository-solid/ semisolid medications for insertion into the vagina Plasters- Plasters are solid or semisolid adhesive masses spread upon a backing material of paper, fabric, moleskin or plastic.

63. LIQUIDS AND GASES

64. Liquids can be used/ administered via various routes of administration e.g. orally, topically, pulmonary and parenterally. The route of administration often determines the vehicle to be used as a carrier for the drug substances. Solubility of the drug substance is also considered and heavily influences the type of liquid preparation to be made eg solution, suspension, emulsion etc.

65. Advantages of liquids Easy to swallow Improved bioavailability Faster onset of action Disadvantages of liquids Bulky Rapid degradation More likely to interact with constituents

66. Types of water Purified water USP - Used for products but not parenteral or ophthalmic pH between 5 and 7 Particles less than 10ppm Obtained by distillation, reverse osmosis or ion exchange Water for injection (WFI) USP - Used as a solvent for parenteral solutions Pyrogen free Obtained by distillation, reverse osmosis or ion exchange

67. Sterile WFI USP- Packaged in single use container not more that 1L Bacteriostatic WFI USP - Sterile WFI containing one or more antimicrobial agent in low doses. Sterile water for inhalation USP - Sterile WFI used in humidifiers. Single dose packaging Sterile water for irrigation USP - Sterile WFI used where large quantities are needed to clean a certain body part

68. Liquids are broadly classified as: Solutions- clear homogenous liquid preparations e.g. syrups, elixirs, spirits, Suspensions- biphasic systems of insoluble solid materials suspended in a liquid medium e.g. lotions Emulsions- stabilized dispersions of two immiscible liquids e.g. depots

69. Syrup-concentrated aqueous solution of a sugar to which medication is added Elixir-contain alcohol as a co-solvent and are pleasantly flavored liquid preparation for nauseous drugs Linctus- viscous liquid oral preparations for relief of cough Oral drops- liquid preparations intended to be administered in small volume

70. Gargles- aqueous solutions for treatment and prevention of throat infection Mouth washes- used for oral hygiene Liniments- can be alcohol based or oil based used for massage Paints- Are aqueous hydro alcoholic, alcoholic or organic solutions of a volatile therapeutic agent applied topically, contain 50-90% of alcoholic content. Lotions- topical preparations for application without friction, contains coolant(alcohol), humectant( glycerol), vehicle, preservative

71. Gaseous dosage form Aerosols / Inhalers- fine solid or liquid drugs in a mixture of inert propellant gas held under pressure in an automized dispenser. It delivers the drug directly into the respiratory tract. Nebulizer- is a device used to administer medication to the airways in form of mist

72. Newer drug delivery systems Nano particles Radiopharmaceuticals Transdermal patches

73. Assignment For each formulation discussed above, give 3 scenarios where the formulation can be best used and 2 scenarios where the formulation would be least suitable. Give reasons for your answers. What are the advantages and disadvantages of gaseous dosage forms?