Compounding of pharmaceutical products listed

Small scale compounding .pptx

1. Small scale compounding Introduction to dosage forms By Hailu E . ( B Pharm ,) 1 4/28/2024 Hailu E.

2. Objectives of the session At the end of the class, you will be able to: Define the term ‘ dosage form ’ (Df) Describe the needs for Dfs Differentiate different types of Dfs 2 4/28/2024 Hailu E.

3. Introduction to dosage forms Dosage forms : Physical forms by w/c drugs administered to patients. Drug substances are rarely administered alone. But rather as a part of formulation in combination with one or more non medicinal agents ( excipients ) which provide varied & specialized functions. 3 4/28/2024 Hailu E.

4. The need for dosage forms It can be difficult or impossible to accurately dosing or handling low dose drug. Drug administration can be impractical, unfeasible. To reduce the drug exposure to the environmental factors. Some drugs can be degraded at GIT (e.g., insulin) Some drugs may cause local irritations or injury when they are present at high concentrations at the site of administration. Some drugs can have unpleasant organoleptic properties (taste, smell, colour) 4 4/28/2024 Hailu E.

5. General considerations in dosage form design Factors that must be considered before a drug substance is successfully formulated in to a Df: PK and Physicochemical properties of the drug Disease consideration Patient consideration 5 4/28/2024 Hailu E.

6. 1. Solid dosage forms Tablets Capsules powders 2. Liquid DFs Solutions Suspensions Emulsions 6 3. Semi-solid dosage forms Ointments Creams Pastes Gels 4. Gaseous DFs Aerosols insuflations etc Classification of pharmaceutical dosage forms according to physical forms 4/28/2024 Hailu E.

7. 1 . Solid dosage forms a) Tablets Compressed solid dosage forms: Oral tablets (intended for oral use) . Vaginal tablets. Dispersible, enteric-coated, modified release, buccal , etc. 7 4/28/2024 Hailu E.

8. b) Capsules Solid dosage forms in gelatin shell . To administer unpleasant ( bad test & odor ) medicaments. 2-types : Hard capsules & soft capsules . Hard capsules usually contain solid medicaments. Consist of cylindrical body & cap, with hemispherical ends. Usually made from gelatin , plasticizer & water . 8 4/28/2024 Hailu E.

9. Soft capsules May be spherical, ovoid, or cylindrical with hemispheric ends . Useful for incorporating solids, liquids & semi-solids . In addition to the ingredients of hard capsule, they contain excess plasticizers which provides flexibility. 9 4/28/2024 Hailu E.

10. c) Suppositories Cylindrical & one or both ends tapered. Inserted into rectum where they melt , dissolve or disperse. Exert local or systemic effect. Weigh 1g (for children) or 2g (for adults) or occasionally 4 g. 10 Pesseries: Are suppositories for insertion into vagina . Are larger than suppositories (3-5 g) in weight. Are globular, oviform or cone shaped. 4/28/2024 Hailu E.

11. d) Powders D rug powder & powdered excipients mixed. Function of the added excipients depends upon the intended use of the product. Coloring, flavouring & sweetening agents . Packed as both bulk & divided powders. Bulk powders usually contain non-potent active ingredients such as antacids. Divided powders are used for more potent drugs where accuracy of dosage is more important. 11 4/28/2024 Hailu E.

12. Dusting powders Finely divided powders for external use ( surface of the skin ). Used as lubricants to prevent friction between skin surfaces and for disinfection and antisepsis in minor wounds. 12 4/28/2024 Hailu E.

13. e) Granules Consist of powder particles that have been aggregated to form a larger particle , which is usually 2-4mm in diameter. May be packed in a unit dose or provided in bulk format. E.g, Some laxatives are presented as granules. 13 4/28/2024 Hailu E.

14. f) Implants Are inserted under the skin by a small surgical incision. Most commonly used for hormone replacement therapy or as a contraceptive. Release of drug from implants is generally slow & long term. E.g, In the case of contraceptive the effect continues up to 3 years or above. 14 4/28/2024 Hailu E.

15. g) Lozenges (Troches) Large tablets designed to be sucked and remain in the mouth for up to 15 minutes. Do not contain disintegrant. API is incorporated into a sugar base, such as sucrose or glucose . Mainly used in mouth & throat infections ( e.g., clotrimazole lozenge ). 15 4/28/2024 Hailu E.

16. 2 . Liquid dosage forms a) Solutions The drug is completely soluble in the vehicle. For some solutions sterility is necessary ( e.g., parentral) Unsterile are used orally or externally on unbroken surfaces. b) Suspensions The AI is insoluble or very slightly soluble in the vehicle. Available for both oral & external use. 16 4/28/2024 Hailu E.

17. c) Emulsions Mixtures of two immiscible liquids , usually oil & water. Stabilized with emulsifying agent . The oil, in a very fine state of subdivision, is dispersed in water( O/W emulsion ) or water dispersed in oil ( W/O emulsion ). 17 4/28/2024 Hailu E.

18. d) Syrups Oral preparations in which vehicle is a concentrated aqueous solution of sucrose or other sugar . Nowadays sucrose is being replaced by sorbitol as the sweetening agent in many preparations to give ‘sugar-free’ syrups to reduce the risk of dental caries . 18 4/28/2024 Hailu E.

19. e) Enemas Aqueous solution which is administered rectally. Used to treat constipation or ulcerative colitis . f) Gargles Aqueous solutions used to treat infections of the throat . Often presented in concentrated form with instructions to the patient for dilution with warm water before use. Should not be swallowed but held in the throat while exhaling through the liquid. 19 4/28/2024 Hailu E.

20. g) Irrigations Solutions of medicaments used to treat infections of the bladder , vagina and less often, the nose . Administered via a thin, soft, rubber or plastic tube known as a catheter (for bladder ) , a vulcanite or plastic pipe (for vagina ) or a specially designed glass irrigator (for nose ). h) Linctuses Viscous, oral preparations that are usually prescribed for the relief of cough . 20 4/28/2024 Hailu E.

21. Containing high proportion of syrup & sometimes, glycerin which, as well as sweet taste , have a demulcent effect on the mucus membrane of the throat. The viscous nature of the preparation coats the throat & helps to alleviate the irritation which is causing the problem. Previously many linctuses contained a level of sucrose; however, many have been reformulated as ‘ sugar-free ’ products to reduce the risk of dental caries . 21 4/28/2024 Hailu E.

22. i) Elixirs Sweetened , flavored , hydro alcoholic solns intended for oral. Non medicated elixirs are employed as vehicles & medicated elixirs are used for the therapeutic effect of the medicinal substances they contain. The therapeutic action of drugs present as elixirs varies widely & includes antihistamines, antibiotics and decongestants. 22 4/28/2024 Hailu E.

23. j) Liniments Liquids for external use . May be alcoholic or oily solutions or emulsions . Used to alleviate discomfort of muscle strains & injuries . B/c of some of the rubefacient ( increase blood flow in the applied area ) nature of some of the ingredients ( turpentine oil & methyl salicylate ). Some sportsmen use them prior to starting sporting activity in an attempt to avoid any muscle damage. Must not be applied to broken skin . 23 4/28/2024 Hailu E.

24. k) Lotions Usually containing suspended insoluble material & applied externally . Different from liniments by being aqueous , rather than oleaginous or alcoholic in nature. Either dabbed on the skin or applied on a suitable dressing & covered with water-proof material to reduce evaporation. Have a verity of uses which include antiseptic , parasiticidal & soothing . 24 4/28/2024 Hailu E.

25. l) Mouthwashes Similar to gargles but are used specifically to treat conditions of the mouth . Less concentrated than gargles. Active ingredients are usually antiseptics. m) Nasal drops Isotonic solutions used to treat conditions of the nose. Locally acting decongestants are commonly presented. The container includes a dropper device to allow the patient to deliver the appropriate dose into the affected nostril (s). 25 4/28/2024 Hailu E.

26. n) Ear drops The drug, or mixture of drugs, is presented as a solution or suspension in a suitable vehicle such as water , glycerol , propylene glycol or alcohol . The drops are inserted into the ear, using dropper . Some vehicles, such as alcohol, may cause a degree of stinging when applied to the ear. 26 4/28/2024 Hailu E.

27. 3. Semi-solid dosage forms a) Ointments Applied to the skin or mucous membrane . The base usually contains the medicament in solution or suspension form. b) Creams Semi-solid emulsions for external use. Types : Aqueous & oily creams in which emulsions are O/W & W/O respectively. The O/W type is relatively non greasy. 27 4/28/2024 Hailu E.

28. c) Pastes Ointment like preparations intended for external application to the skin. Differ from ointments primarily in that they generally contain a larger proportion of solid materials & as a consequence are thicker & stiffer than ointments. Often used in the treatment of oozing lesions , where they act to absorb serous secretions. 28 4/28/2024 Hailu E.

29. d) Gels Organic or inorganic colloids rich in liquid. Consist of hydrated large molecules or granules of the dispersed phase intimately associated with the dispersion medium. Usually transparent or translucent . Medicated & non medicated . Medicated gels are often used for topical or on mucus membrane. 29 4/28/2024 Hailu E.

30. 4. Gaseous dosage forms a) Aerosols Consists of pressurized packs which contain the drug in solution or suspension & a suitable propellant (gas). Used to apply drug in the RT (e.g., asthma) & skin (e.g., muscle sprains & injuries). These devices are fitted with metering valve which allows a known dose of drug to be delivered each time the device is fired. 30 4/28/2024 Hailu E.

31. b) Insufflations Medicated dusting powders that are blown by insufflator (a device similar to atomizer) into regions such as the nose, throat, body cavities & the ear to which it would be difficult to apply the powder directly. 31 4/28/2024 Hailu E.

32. Pharmaceutical Ingredients

33. Objectives At the end of this session, you will be able to: Define pharmaceutical ingredients Mention types of excipients used in liquid and semi solid dosage forms 33 4/28/2024 Hailu E.

34. Introduction to Pharmaceutical Ingredients Drug substances are given as part of a formulation in combination with one or more non- medicinal agents. Generally, pharmaceutical ingredients are categorized in to: Active pharmaceutical ingredient (API)- have pharmacologic effect. Inactive pharmaceutical ingredients (Additives or excipients) -‘have no pharmacologic effect’. 34 4/28/2024 Hailu E.

35. Pharmaceutical solvents Used to dissolve API in preparation of a solution. Aqueous or non aqueous. Water-miscible or water immiscible . Water miscible : ethanol, aromatic water, glycerol, propylene glycol, isopropyl alcohol, dimethyl sulfoxide, etc. Water immiscible: almond oil, castor oil, arachis oil, olive oil, diethyl ether, liquid paraffin, isopropyl myristate, etc 35 4/28/2024 Hailu E.

36. Preservatives Used in liquid & semisolid preparations to prevent growth of microorganisms . Antioxidants Used to prevent deterioration by oxidation . Are easily oxidizable. Act by possessing lower oxidation potential than the APIs. 36 4/28/2024 Hailu E.

37. Buffers Resist change in pH upon dilution/addition of acid or alkali. Chemically they are combinations of weak acid & salt of the weak acid or weak base & salt of the weak base. Viscosity inducing agents Used in suspensions to deter sedimentation , in ophthalmic solutions to enhance contact time (e.g. methyl cellulose), to thicken topical creams, etc. 37 4/28/2024 Hailu E.

38. Surfactants ( surface active agents ) Substances having a tendency to accumulate at the boundary between two immiscible phases (oil & aqueous phases) because of their amphipathic nature . May be used as wetting agents in suspensions & emulsifiers in emulsions . Coloring agents Substances that impart color to enhance the appearance of the preparations or to increase their acceptability to the patient. 38 4/28/2024 Hailu E.

39. Flavors Used to impose a pleasant flavor to oral preparations. Sweetening agents Used to impart sweetness to a preparation (e.g. sucrose, glucose, sorbitol, saccharin sodium, Mannitol, glycerin, dextrose, aspartame) Ointment, cream & paste bases They are semisolid vehicles for medicated ointments. May be prepared from petrolatum, hard paraffin, mineral oil, wool fat, etc. 39 4/28/2024 Hailu E.

40. x. Disintegrants : Overcome the cohesiveness imparted during compression. It increases break up → increase surface area → increase dissolution → increase absorption • Eg . Starch, Alginic acid, Polacrilin potassium, Sodium alginate, Microcrystalline cellulose XI . Lubricants : Reduce friction during tablet compression Enhance the flow of the material Minimize wear of the part of the machines Prevent fill material from sticking Produce tablets with sheen E.g. Fine silica, magnesium stearate, Talc 40 4/28/2024 Hailu E.

41. XII. Adhesives or Binders : Promote adhesion in Granules and tablets. E.g. Acacia, Alginic acid, Carboxymethylcellulose sodium, Compressible sugar, Ethylcellulose , Gelatin, Liquid glucose, Methylcellulose, Povidone, Pregelatinized starch, dibasic calcium phosphate, polyvinyl pyrollidin e . XIII Other pharmaceutical ingredients Ointment bases : Parts of an ointment which is used as a Vehicle Suppository bases : Vehicles for suppositories Gelling agents : They are ingredients that give the preparation a gel like consistency. Some of the gelling agents used are: Tragacanth - bassorin pastes, Sodium alginate, Pectin, Starch . Diluents or Fillers : Create tablet of proper size and consistency. Quantity of AI is small or difficult to compress so that diluents and fillers are added . 41 4/28/2024 Hailu E.

42. Routes of drug administration

43. Objectives At the end of the session, you will be able to: Define routes of drug administration. Differentiate different routes of drug administration. Mention their advantages & disadvantage. Describe Dfs suitable for each route of administration. 43 4/28/2024 Hailu E.

44. Routes of drug administration The way through w/c the Df is administered into body. For a drug to bring its beneficial effect it has to be administered into the body by convenient route. Can be divided into: Enteral, Parenteral, Topical, Respiratory route and Miscellaneous routes. 44 4/28/2024 Hailu E.

45. Enteral routes are routes related with GIT and include : Oral Sublingual Buccal Rectal Parentral route include: Intravenous (IV) Subcutaneous (SC) Intramuscular (IM) Intraspinal Intrarterial Intrapretonial 45 Topical route Respiratory route 4/28/2024 Hailu E.

46. Oral route Also called per os ( p.o ) The most commonly used route for drug administration. The most popular Dfs are tables , capsules , solutions , suspensions & emulsions . Can produce either a systemic or a local effect. Advantages Simplest , convenient (self-administration of drug can be carried out) and if used properly, it is also the safest route . 46 4/28/2024 Hailu E.

47. Disadvantages Relatively slow onset of drug action. Unpleasant test of some drugs can be felt. Irritation of gastric mucosa by some drugs. May be irregular absorption from the GIT (e.g., some foods delay absorption of drugs) Altered drug solubility by the presence of other substances in the GIT( e.g., calcium forms complex with tetracycline) 47 4/28/2024 Hailu E.

48. Unsuitable route in unconscious or vomiting patients. Gastric emptying can be influenced by food, drugs, disease state & posture . Some drugs are destroyed by enzymes & other secretions found in GIT (e.g., insulin & penicillin become inactivated by the action of stomach acid) Subject to hepatic metabolism or first pass effect (presystemic metabolism): Because blood supply from GIT passes through liver via the hepatic portal system, e.g., lidocaine 48 4/28/2024 Hailu E.

49. Buccal route The Df is positioned beside the mucus membrane lining the checks . Tablet or spray are administered & absorbed from buccal cavity. Water is not used for taking the dosage form. The highly vascular nature of tongue & buccal cavity and the presence of saliva which can facilitate the dissolution of the drug, make this a highly effective and useful route for drug administration. 49 4/28/2024 Hailu E.

50. Advantages Relatively quick onset of action (due to rapid absorption of drugs). Drugs can be administered to unconscious patients. No deactivation of drug by gastric fluid. No “first-pass” effect. Disadvantage Unpleasant test of some drugs can be felt. It is useful for small dose drugs. Inconvenient 50 4/28/2024 Hailu E.

51. Sublingual route The Df is placed on the floor of the mouth (palate) or under the tongue. Formulations : chewing gums, fast-dissolving tablets and mucoadhesive patches. E.g, nitroglycerine tablets . 51 4/28/2024 Hailu E.

52. Advantages Relatively quick onset of action( due to rapid absorption of drugs) Drugs can be administered to unconscious patients No deactivation of drug by gastric fluid No "first-pass” effect Disadvantages Unpleasant test of some drugs can be felt. It is useful for small dose drugs Inconvenient 52 4/28/2024 Hailu E.

53. Rectal route 53 4/28/2024 Hailu E.

54. Df is placed in the rectum from where the drug is released to give a local effect or may be absorbed to give systemic effect . Drugs are formulations: Liquids, solids & semi-solid Dfs. The rectum is supplied by 3 veins: The middle The inferior (lower) The upper Hence, depending on the position within the rectum , only some drug will be subject to the first pass effect. 54 Drain directly into the systemic circulation Drains into the portal system which flows into the liver 4/28/2024 Hailu E.

55. Advantages To provide a local effect for the treatment of infection and inflammation , e.g. hemorrhoids, proctitis. To promote evacuation of the bowel to relieve constipation or to cleanse the bowel prior to surgery. To provide systemic drug absorption in situations where oral drug absorption is not recommended. Examples: patients who are unconscious , e.g. in intensive care or who are postoperative. 55 4/28/2024 Hailu E.

56. Vomiting , e.g. gastrointestinal infection, migraine. To administer gastroirritant drugs , particularly in chronic usage (e.g. non-steroidal anti-inflammatory agents). Drugs that are prone to degradation in the stomach. Drugs which erratically absorbed from the upper GIT. Drugs that are extensively first-pass metabolized . 56 4/28/2024 Hailu E.

57. Disadvantages Uncomfortable. Specialist advice is required concerning the administration. Its absorption is slow & prone to large intrasubject and intersubject variability. Rectal administration may result in the development of local side effects , in particular proctitis . 57 4/28/2024 Hailu E.

58. Vaginal route Formulations like; Pesseries , tablets , solutions , sprays , creams , ointments & foams . Most often this route is used for a local effect ( used to treat vaginal infections & vaginitis ). However, drugs absorbed from the vagina are not subject to the first pass effect & systemic bioavailability better than the oral route. 58 4/28/2024 Hailu E.

59. Advantages Possibility of self-administration. High vascularization. Relatively low enzymatic activity (e.g.,trypsin and chymotrypsin are absent) Bypass hepatic first pass-effect. Increased permeability for some drugs when comparing to the oral or other routes. 59 4/28/2024 Hailu E.

60. Disadvantages Social taboo. Removal of dosage form after administration. Only few drugs are administered by this route. Variability in drug absorption related with menstrual cycle, menopause & pregnancy. Influence with sexual intercourse. Gender specificity. 60 4/28/2024 Hailu E.

61. Parentral route The term used to describe drug administration by injection . Within this there are variety of routes. The main ones are: Intravenous route (IV) Intramuscular route (IM) Subcutaneous route (SC) 61 4/28/2024 Hailu E.

62. 62 4/28/2024 Hailu E.

63. Intravenous route (IV ), where drugs are injected directly into the vein. The surest way of introducing drug into systemic circulation. Permit rapid onset of action ( no absorption of drug ). Large volume of pharmaceutical preparations can be administered than other routes. 63 4/28/2024 Hailu E.

64. Intramuscular route (IM) Drugs are injected into muscle from where they are absorbed due to the perfusion of the muscle by blood. Usually injected at deltoid & gluteus muscle. Can be used to produce a fairly fast onset of action when the drug is formulated as an aqueous solution. 64 4/28/2024 Hailu E.

65. A slower and more prolonged action will occur when the drug is presented as a suspension or in non aqueous vehicle such as ethylene glycol or peanut oil . As the vehicle diffuses out of the muscle, the drug precipitates at the site of injection. The drug then dissolves slowly, providing a sustained release over extended period of time. 65 4/28/2024 Hailu E.

66. Subcutaneous route (SC), where drugs are injected into the subcutaneous fat layer of the skin. The easiest & least painful type of injection. Used for administering aqueous solution and specialized preparations. It requires absorption. Volume of preparations to be injected is smaller than in IV and IM routes ( usually not more than 2 ml). 66 4/28/2024 Hailu E.

67. Absorption of drug from the site of injection for both IM and SC can be increased by massaging, heating and adding an enzyme hyaluronidase The rate of absorption from IM and SC routes can be reduced by epinephrine . Minute amount of epinephrine are some times administered combined with drug to restrict its area of action. Epinephrine acts as local vasoconstrictor and decrease removal of drug such as lidocaine from the site of administration. 67 4/28/2024 Hailu E.

68. Advantages of parenteral route : Useful to administer drugs in emergency conditions. When patients are unconscious. In case when drugs are inactivated or poorly absorbed following oral administration. Disadvantages of parenteral route : Irreversible Injected drugs cannot be recalled by strategies such as emesis or binding to activated charcoal. Painful & inconvenient 68 4/28/2024 Hailu E.

69. Respiratory route Inhalation through nose or mouth to produce either local or systemic effects. Drugs are delivered as aerosol or very fine solid particle form. Used predominantly for local administration to treat respiratory conditions such as asthma . A major benefit: the drug dose required to produce the desired effect is much smaller than for the oral route , with a consequent reduction in side-effects. 69 4/28/2024 Hailu E.

70. This route is being increasingly recognized as a useful means for administering therapeutic agents emerging from biotechnology requiring systemic distribution & targeted delivery, such as peptides & proteins . Because of the high blood flow to the lungs and their large surface area, drug absorption by this route is extremely rapid . 70 4/28/2024 Hailu E.

71. Topical route Applied mainly for local action to the eye, ear & nose are also regarded as topical administration. Drugs: antiseptics, antifungals, anti-inflammatory agents , skin emollients, protective agents, etc. 71 4/28/2024 Hailu E.