1. INTEGRATED PHYSICAL PHARMACY & PHARMACEUTICS- I PHAR2091 By: Assefa A 12/19/2017 Assefa A 1

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3. Outline Introduction to pharmaceutics Introduction to pharmaceutics Pharmaceutical dosage forms Pharmaceutical dosage forms Pharmaceutical excipients Pharmaceutical excipients Routes of drug administration Routes of drug administration 12/19/2017Assefa A3

4. Objectives Objectives After this lesson the students are expected to  Know what does pharmaceutics mean  Know what active pharmaceutical ingredient is  Understand the meaning and function of pharmaceutical excipients  Identify different excipients used for different types of dosage forms  Know about routes of drug administration 12/19/2017Assefa A4

5. 12/19/2017Assefa A5 Pharmaceutics and physical pharmacy Definition:  pharmaceutics is the conversion of drug substances in to medicines suitable for administration by or to patients.  It is the most diverse of all the subject areas in pharmaceutical science. A multidisciplinary subject Introduction

6. Pharmaceutics…….. It deals with:  Investigations of physical and chemical properties of drug molecules necessary for efficient design of dosage forms. Physical pharmacy  The design and formulation of medicines. Dosage form design 12/19/2017Assefa A6

7. 12/19/2017 Assefa A7  Monitoring how drug products are absorbed, distributed, metabolized, and excreted in the body: Bio pharmaceutics and pharmacokinetics  Manufacture of medicines on both a small (compounding) and a large (industrial) scale: Extemporaneous compounding & Industrial pharmacy  Cultivation, avoidance and elimination of microorganisms in medicines :Pharmaceutical microbiology

8. Physical pharmacy Gives the physicochemical basis for understanding pharmaceutical formulation and drug delivery. State of matters Phase Equilibrium Interfacial Phenomena Solubility and distribution phenomenon Diffusion Micrometrics Rheology 12/19/2017 Assefa A8

9. Physical pharmacy……  The need for integration of physical pharmacy and pharmaceutics is to equip the students both with:  the art and science of dosage form design and  The physicochemical considerations for that specific dosage form within a single course. 12/19/2017Assefa A9

10. Pharmaceutical dosage form Definition: Dosage forms are the means by which drug molecules are delivered to sites of action within the body. They are designed to facilitate the administration of drug substances. Dosage forms are also called drug delivery systems. 12/19/2017Assefa A10

11. Dosage Forms……  Pharmaceutics deals with the formulation of a pure drug substance (active pharmaceutical ingredient – API) into a dosage form.  API is a chemical compound with pharmacological (or other direct effect ) effect intended for use in diagnosis, treatment or prophylaxis of diseases. 12/19/2017Assefa A11

12. Dosage Forms……  Generally, we prefer drug delivery systems because direct clinical use of the active drug substances “as they are” is rare due to a number of reasons: API handling can be difficult or impossible (e.g., low mg and µg doses). Accurate drug dosing can be difficult or impossible. API administration can be impractical, unfeasible or not according to the therapeutic aims. 12/19/2017Assefa A12

13. Dosage Forms……. Insertion of drugs into body cavities (rectal, vaginal) is not possible. Some API can benefit from reducing the exposure to the environmental factors (light, moisture…), or they need to be chemically stabilized due to the inherent chemical instability. API can be degraded at the site of administration (e.g., low pH in stomach). 12/19/2017Assefa A13

14. Dosage Forms…… API may cause local irritations or injury when they are present at high concentrations at the site of administration. API may have unpleasant organoleptic qualities (taste, smell – compliance!). 12/19/2017Assefa A14

15. Dosage Forms…….  Pharmaceutical dosage form  Determines the physical form of the final pharmaceutical preparation.  Is a drug delivery system which is formed by technological processing (drug formulation).  Must reflect therapeutic intentions, route of administrations, dosing, etc. 12/19/2017Assefa A15

16. DF preparation 12/19/2017Assefa A16 Preparatio n processes API + + additives (excipients) MEDICINES DFs

17. Types of Dosage Forms 12/19/2017Assefa A17 They are classified according to: Route of administration Oral Topical Rectal Parenteral Vaginal Inhaled Ophthalmic Physical form Solid Semisolid Liquid Gas Origin Compounded manufactured

18. Classification of PDF according to physical properties  Solid dosage forms  Semisolid dosage forms  Liquid dosage forms  Gaseous dosage forms 12/19/2017Assefa A18

19. DOSAGE FORMS….. 1.Solid dosage forms I. Unshaped (without specific shape) A. Powders There are two kinds of powder intended for external/internal use. 1-Bulk Powders:  Are multidose preparations consisting of solid, dry particles usually contain non-potent medicaments such as antacids.  The powder is then usually dispersed in water. 12/19/2017Assefa A19

20. DOSAGE FORMS…… 2-Divided Powders:  are single-dose presentations of powder (a small sachet) that are intended to be issued to the patient as such, to be taken in or with water. 12/19/2017Assefa A20

21. DOSAGE FORMS B. Granules They are consisting of solid, dry aggregates of powder particles often supplied in single-dose sachets. Some granules are placed on the tongue and swallowed with water, others are intended to be dissolved in water before taking. Effervescent granules evolve carbon dioxide when added to water. 12/19/2017 Assefa A 21

22. DOSAGE FORMS….. II. Shaped A.Tablets A hard, compressed medication in round, oval or square shape. The API will be compressed along with other pharmaceutical excipients. Used as oral dosage form. The excipients include:  Binders, glidants, lubricants, Disintegrants, Sweeteners, flavors, Colorant,etc. 12/19/2017 Assefa A 22

23. DOSAGE FORMS……. A coating may be applied to: 1- hide the unpleasant taste of the tablet's components. 2- make the tablet smoother and easier to swallow 3- make it more resistant to the environment 4- control the toxicity of API in GIT 12/19/2017 Assefa A 23

24. A. Tablets Classification of tablets a. Buccal and sublingual tablet Sublingual and buccal medications are administered by placing them in the mouth, either under the tongue (sublingual) or between the gum and the cheek (buccal). The medications dissolve rapidly and are absorbed through the mucous membranes of the mouth, where they enter into the bloodstream. e.g. vasodilators 12/19/2017 Assefa A 24

25. b. Effervescent tablet Effervescent tablets are uncoated tablets that generally contain acid substances (citric and tartaric acids) and carbonates or bicarbonates and which react rapidly in the presence of water by releasing carbon dioxide ↔ disintegration 12/19/2017 Assefa A 25

26. Effervescent tablet Effervescent tablet They are intended to be dissolved or dispersed in water before use, providing: ◦ Very rapid tablet dispersion and dissolution → rapid absorption ◦ Pleasant tasting carbonated drink. 12/19/2017Assefa A26

27. 12/19/2017Abyou & Manaye27  Effervescent tablets are dropped into a glass of water before administration, during which carbon dioxide is liberated.  This facilitates tablet disintegration and drug dissolution; the dissolution of the tablet should be complete within a few minutes.  As mentioned above, the effervescent carbon dioxide is created by a reaction in water between a carbonate or bicarbonate and a weak acid such as citric or tartaric.

28. 12/19/2017Abyou & Manaye28  Effervescent tablets are used to obtain rapid drug action, for example for analgesic drugs or to facilitate the intake of the drug, for example for vitamins.  The amount of sodium bicarbonate in an effervescent tablet is often quite high(about1g)

29. c. Chewable tablet Tablets are chewed within the buccal cavity prior to swallowing. Advantage: ◦ children and adults who have difficulty in swallowing conventional tablets e.g. vitamin products. ◦ antacid formulations in which the size of the tablet is normally large. 12/19/2017 Assefa A 29

30. B. Capsules Capsules  A medication in a gelatin container. Advantage:  mask the unpleasant taste of its contents.  There are two types of capsules 12/19/2017 Assefa A 30

31. DFs 1. hard-shelled : used for dry, powdered ingredients. 2. soft-shelled : primarily used for oils and for active ingredients that are dissolved or suspended in oil. 12/19/2017 Assefa A 31

32. C. Lozenge It is consisting of sugar and gum  the latter giving strength and cohesiveness to the lozenge and facilitating slow release of the medicament. It is used to medicate the mouth and throat for the slow administration of indigestion or cough remedies.  dissolved slowly in the mouth  lubricate and soothe irritated tissues of the throat. 12/19/2017 Assefa A 32

33. D. Suppository It is a small solid medicated mass, usually cone- shaped,that is inserted either into the rectum (rectal suppository) or vagina (vaginal suppository) where it melts at body temperature. 12/19/2017 Assefa A 33

34. E. Pessary  Pessaries are designed for insertion into the vagina at where they melt or dissolve. There are three types: A- Moulded: are cone shaped and prepared in a similar way to Moulded suppositories. B- Compressed: made in a variety of shapes and are prepared by compression in a similar manner to oral tablets. C- Vaginal capsules: are similar to soft gelatin oral Capsules differing only in size and shape. 12/19/2017 Assefa A 34

35. F. Implants  Sterile disks inserted surgically into body tissues and designed to release drug(s) over extended period of time. 12/19/2017 Assefa A 35

36. 2. Semisolid dosage forms A. Ointments are semi-solid, greasy preparations for application to the skin, rectum or nasal mucosa (semisolid suspension). form a transparent unbroken relatively water impermeable film in the skin. used as: ◦ emollients : Effective barrier against moisture loss ◦ to apply suspended or dissolved medicaments to the skin. 12/19/2017 Abyou & Manaye36

37. Semisolid dosage forms B. Pastes o are basically ointments into which a high percentage of insoluble solid has been added. o solid particles (> 25%) are dispersed in ointments – mostly oleaginous (Petrolatum) o Stiff:The extraordinary amount of particulate matter(ZnO) o Like ointments, paste forms an unbroken relatively water impermeable opaque film. Therefore, can be used as an effective sun block accordingly. 12/19/2017 Assefa A 37

38. Semisolid dosage forms C. Creams  are semi-solid emulsions, that is mixtures of oil and water. They are two types : A. O/W: small droplets of oil dispersed in a continuous aqueous phase. They are more comfortable and cosmetically acceptable as they are less greasy more easily washed off using water. B.W/O : small droplets of water dispersed in a continuous oily phase. Advantage: Release drug readily More moisturizing Disadvantage: More difficult to handle 12/19/2017 Assefa A38

39. Semisolid dosage forms d. Gels (Jellies) Are semisolid DFs composed of a liquid phase within a network structure of a solid gelling agent (consisting of natural or synthetic gum or aluminium hydroxide). They are used for medication, lubrication and some miscellaneous applications like carrier for spermicidal agents to be used intra vaginally. 12/19/2017 Assefa A 39

40. Semisolid dosage forms E. Lotions These are either liquid (aqueous) or semisolid preparations containing one or more APIs used for external application without friction. They are either dabbed on the skin or applied on a suitable dressing and covered with a waterproof dressing to reduce evaporation. 12/19/2017 Assefa A 40

41. Semisolid dosage forms F. Collodion  It is a solution of nitrocellulose in ether or acetone.  As the solvent evaporates, it dries to a celluloid-like film.  used in Treatment of warts by keratolysis. 12/19/2017 Assefa A 41

42. Semisolid dosage forms G. Liniments Are alcoholic or oil-based solutions or emulsions containing therapeutic agents intended for application to the skin to soothe pain. These preparations could be liquid or semisolid. Most are massaged into the skin (e.g. counter-irritant). Liniments should not be applied to broken skin. 12/19/2017 Assefa A42

43. 3. Liquid dosage forms A. Solutions  one homogenous phase, prepared by dissolving one or more solutes in a solvent.  Oral solutions are clear liquid preparations for oral use containing one or more active ingredients dissolved in a suitable vehicle. 12/19/2017 Assefa A 43

44. 3. Liquid dosage forms B. Syrup It is a concentrated aqueous solution of a sugar, usually sucrose. No need of other sweetening agents and viscosity-modifying agents. No addition of preservatives is required. 12/19/2017 Assefa A44 High concentration of sucrose

45. 3. Liquid dosage forms C. Elixir It is clear hydro-alcoholic solution for oral use The vehicle may contain a high proportion of ethanol or sucrose together with antimicrobial preservatives. But if the alcohol content > 12% v/v alcohol No need of preservatives: due to the antimicrobial effect of alcohol. 12/19/2017 Assefa A 45

46. 3. Liquid dosage forms d. Linctuses Are viscous, liquid oral preparations that are usually prescribed for the relief of cough. Usually contain a high proportion of syrup and glycerol which have a demulcent effect on the membranes of the throat. The dose volume is small (5ml) and, to prolong the demulcent action, they should be taken undiluted. 12/19/2017 Assefa A 46

47. 3. Liquid dosage forms e. Gargles They are aqueous solutions used in the prevention or treatment of throat infections. Usually they are prepared in a concentrated solution with directions for the patient to dilute with warm water before use. f. Mouthwashes These are similar to gargles but are used for oral hygiene and to treat infections of the mouth. 12/19/2017 Assefa A 47

48. 3. Liquid dosage forms g. Enema  are pharmaceutical solutions that are administered in to rectum and colon via the anus. Types of enema: 1.Evacuant: used as a bowel stimulant to treat constipation. E.g. soft soap enema & Mgso 4 enema The volume of evacuant enemas may reach up to 2 liters. They should be warmed to body temperature before administration. 12/19/2017 Abyou & Manaye48

49. 3. Liquid dosage forms 2. Retention: - Their volume does not exceed 100 ml. - No warming needed. - Administered into the blood stream where it is impossible to deliver a medication by mouth, such as antiemetics. e.g. nutrient enema which contains carbohydrates, vitamins & minerals. 12/19/2017 Assefa A 49

50. 3. Liquid dosage forms h. emulsion:  Oral emulsions are stabilized oil-in-water dispersions, either or both phases of which may contain dissolved solids.  A dispersion system consisting of two immiscible liquids. ◦ o/w or w/o  cloudy appearance 12/19/2017 Assefa A50

51. 3. Liquid dosage forms i. suspension: Are liquid preparations for oral use containing one or more active ingredients suspended in a suitable vehicle. Show a sediment which is readily dispersed on shaking to give a uniform suspension which remains sufficiently stable to enable the correct dose to be delivered. 12/19/2017Assefa A51

52. 3. Liquid dosage forms A dispersion system where solid particles (dispersed phase) are dispersed in liquid phase (dispersion medium). According to the size of dispersed particles (1 nm- 0.5 mm) a molecular, colloidal and coarse dispersions can be distinguished. 12/19/2017Assefa A52

53. 3. Liquid dosage forms j. Paints:  Are aqueous, hydro-alcoholic, alcoholic or organic solutions of a therapeutic agent that are applied to the skin or mucous membranes.  Skin paints contain volatile solvent that evaporates quickly to leave a dry resinous film of medicament.  The use of paints nowadays is limited due to the emergence of more elegant dosage forms. 12/19/2017 Assefa A53

54. 4. Gaseous dosage forms Pressurized dispensers (aerosol sprays) Several different types of pharmaceutical product may be packaged in pressurized dispensers, known as aerosols. May be used as surface disinfectants, wound or burn dressing, relieve irritation of bites. 12/19/2017 Assefa A 54

55. 4. Gaseous dosage forms Nebulizer or (atomizer) A nebulizer is a device used to administer medication to people in forms of a liquid mist to the airways. commonly used in treating asthma, and other respiratory diseases. It pumps air or oxygen through a liquid medicine to turn it into a vapor, which is then inhaled by the patient. Nebulizers are usually reserved only for serious cases of respiratory disease, or severe attacks. 12/19/2017 Assefa A 55

56. 4. Gaseous dosage forms Inhaler: Inhalers are solutions, suspensions or emulsion of drugs in a mixture of inert propellants held under pressure in an aerosol dispenser. Release of a dose of the medicament in the form of droplets from the container through a spring-loaded valve incorporating a metering device. The patient then inhales the released drug through a mouthpiece. 12/19/2017 56

57. 4. Gaseous dosage forms In some types, the valve is actuated by finger pressure, in other types the valve is actuated by the patient breathing in through the mouthpiece. It is commonly used to treat asthma and other respiratory problems.  Because they are : cheaper more portable and carry less risk of side effects 12/19/2017 Assefa A 57

58. Pharmaceutical Excipients 12/19/2017 Assefa A 58

59. Pharmaceutical Excipients  Medicinal dosage forms, regardless of composition or mode of use, must meet the following requirements that underpin efficacy, safety, and quality: 1.Contain an accurate dose. 2.Be convenient to take or administer. 3.Provide the drug in a form for absorption or other delivery to the target. 12/19/2017 Assefa A 59

60. Pharmaceutical Excipients 4.Retain quality throughout the shelf life and usage period. 5.Be manufactured by a process that does not compromise performance and that is reproducible and economical. 12/19/2017Assefa A60

61. Pharmaceutical Excipients No active pharmaceutical ingredients have meet all these criteria. Therefore, it is necessary to add other materials to make good any shortfalls. Consequently, every medicinal product is a combination of the drug substance and excipients.  And generally, excipients are indispensable components of medicinal products and in most cases comprise the greatest proportion of the dosage unit. 12/19/2017 Assefa A 61

62. Pharmaceutical Excipients Definition: ◦ Any substance other than the active drug which has been appropriately evaluated for safety and is included in a drug delivery system to either:  Aid processing of the system during manufacture.  Protect, support, or enhance stability &bioavailability.  Assist in product identification.  Enhance any other attribute of the overall safety and effectiveness of the drug product during storage and use. 12/19/2017 Assefa A 62

63. Pharmaceutical Excipients General criteria for excipients: ◦ Physiological inertness ◦ Physical and chemical stability ◦ Conformance to regulatory agency requirements ◦ No interference with drug bioavailability ◦ Absence of pathogenic microbial organisms ◦ Commercially available at low cost 12/19/2017 Assefa A 63

64. Pharmaceutical Excipients  In reality, no single excipient would satisfy all the criteria; therefore, a compromise of the different requirements has to be made. 12/19/2017 Assefa A 64

65. Types of excipients Excipients are sub-divided into various functional classifications, depending on the role that they are intended to play in the resultant formulation. The role of excipients varies substantially depending on the individual dosage form. 12/19/2017 Assefa A 65

66. 1. Excipients for solid dosage forms a. Diluents (or fillers ) Diluents are fillers used to increase the bulk volume of a tablet or capsule (5- 80%). Increase the mass of the tablets and capsule that contain a low concentration of therapeutic agent. Diluents must exhibit good compression properties and be inexpensive, compatible,inert and resistant to microbial growth. 12/19/2017 Assefa A 66

67. Classification of diluents Natural diluents Natural diluents ◦ Starch (old) ◦ Soya bean powder (newly introduced) Organic diluents Organic diluents ◦ Lactose   lactose mono hydrate  anhydrous lactose  spray dried lactose micro crystalline cellulose (MCC) ◦ sucrose, mannitol, sorbitol, micro crystalline cellulose (MCC) Inorganic diluents Inorganic diluents ◦ Dibasic calcium phosphate anhydrate (dihydrate) ◦ Tribasic calcium phosphate 12/19/2017 Assefa A 67

68. b. Binders Binders are predominantly (but not exclusively) polymeric components used to hold API and excipient in a cohesive mix. ◦ Give adherence to powder mixtures → necessary mechanical strength In this role, binders are either added as a solution or as a solid into the powder mix (following which the granulating fluid, typically water, is added). 12/19/2017 Assefa A 68

69. Classification of binders According to their solubility According to their solubility ◦ Insoluble in water eg starch mucilage ◦ Soluble in water eg. HPMC ◦ Soluble in water and ethanol Polyvinylpyrrolidone (Povidone) eg. Polyvinylpyrrolidone (Povidone) According to their chemical source According to their chemical source ◦ Saccharides and their derivatives  Disaccharides: sucrose, lactose  Polysaccharides and their derivatives  Starch, MCC, HPMC 12/19/2017 Assefa A 69

70. Binders ◦ Natural gum: acacia, tragacanth ◦ Protein: gelatin polyvinylpyrrolidone(PVP)polyethylene glycol(PEG) ◦ Synthetic polymers: polyvinylpyrrolidone(PVP), polyethylene glycol(PEG) 12/19/2017 Assefa A 70

71. c. Disintegrants  Facilitate the breakdown of the tablet into granules upon entry into the stomach (15 minutes) (5-20 %) Mode of action:  Increase the porosity and wettability of the compressed tablet matrix  Water uptake rupturing the intra- particle cohesive forces that hold the tablet together → disintegration 12/19/2017 Assefa A 71

72. Disintegrants  Operate by swelling in the presence of aqueous fluids Water uptake → swelling →physical rupture →widened the channels for penetration of water → disintegration Example: sodium starch glycolate, crospovidone, croscarmellose sodium 12/19/2017 Assefa A 72

73. d. Lubricants reduce friction These are used to reduce friction between powders and metal surfaces during tablet manufacture. During compression lubricants act at the interface between the face of the die and the surface of the tablet. hydrophobic Lubricants tend to be hydrophobic, so their levels (typically 0.3 – 2%) need to be optimized  Under-lubricated blends tend to flow poorly and show compression sticking problems.  Over-lubricated blends can adversely affect tablet hardness and dissolution rate. ◦ Example: Magnesium stearate 12/19/2017Assefa A73

74. e. Glidants flow properties of the powders Act to enhance the flow properties of the powders within the hopper and into the tablet die in the tablet press (0.1-2 %). to locate within the spaces between the particles/granules By reducing the friction between the powders/granules due to the ability of the particles of the glidants to locate within the spaces between the particles/granules  Glidant particles to be small  Arrange at the surface of the particles/granules Colloidal silicon dioxide Example: Colloidal silicon dioxide (traditionally, talc was used) 12/19/2017 Assefa A 74

75. f. Organoleptic excipients Sweetening agents/flavoring agents Sweetening and flavoring agents are employed to control the taste and hence the acceptability of tablets. More important ◦ If the conventional tablet contains a bitter drug ◦ If the tablet is a chewable tabletColorants Colored tablets are generally formulated either to improve the appearance or to identify the finished product uniquely. 12/19/2017 Assefa A 75

76. 2. Excipients For liquid dosage forms a. The vehicle The preferred and most commonly used vehicle in liquid dosage forms is Purified Water USP, due to :  Low cost & toxicity  Physical compatibility  Good solubilizing powerDisadvantage  Instability of hydrolytically unstable drugs  Being good vehicle for microbial growth Co-solvents are employed to increase the solubility of the therapeutic agent within the formulation.  Glycerol and ethanol 12/19/2017 Assefa A 76

77. b. Buffers Buffers are employed within pharmaceutical solutions to control the pH of the formulated product. Typically pH control is performed: To maintain the solubility of the API in the formulated product. To enhance the stability of products in which the chemical stability of API is pH-dependent. 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) 12/19/2017 Assefa A 77

78. c. Antimicrobial preservatives Preservatives are used to control the microbial bio- burden of the formulation. Ideally, preservatives should exhibit the following properties: Possess a broad spectrum of antimicrobial activity. Be chemically and physically stable over the shelf-life of the product. Have low toxicity Example: Benzoic acid and salts (0.1–0.3%) Sorbic acid and its salts (0.05–0.2%) Alkyl esters of parahydroxybenzoic acid (0.001– 0.2%) 12/19/2017 Assefa A 78

79. d. Antioxidants enhance the stability of therapeutic agents degradation by oxidation. Included to enhance the stability of therapeutic agents that are susceptible to chemical degradation by oxidation. Used to control oxidation of  API, Preservative  vehicle, e.g. oils or fats susceptible to β- oxidation (rancidification)  Colorants (ageing discoloration) They are sacrificial (more oxidisable than API, preservative, etc). 12/19/2017 Assefa A 79

80. Antioxidants Levels will reduce with time…. need to be monitored by specific assay.  Light exposure and metal ion impurities can accelerate oxidative degradation and hence depletion of API. Examples: ◦ Sodium sulphite ◦ sodium metabisulphite ◦ sodium formaldehyde ◦ Sulphoxylate ◦ ascorbic acid ◦ Butylated hydroxytoluene (BHT) 12/19/2017 Assefa A 80

81. e. Viscosity-enhancing agents Suspension stabilizers: prevent settling/sedimentation thixotropic ( They usually modify viscosity and are often thixotropic (where viscosity is dependent on applied shear and exhibits ‘shear thinning’)  Easily poured when shaken  Must permit accurate dosing with chosen method (e.g. graduated syringe, spoon)  Quickly reforms ‘gel-like’ structure 12/19/2017 Assefa A 81

82. Viscosity-enhancing agents Work by entrapment of solid particles, e.g. API, in a viscous or even gel-like’ structure. Example:  Water-soluble- methylcellulose, or hydroxyethylcellulose  Water-insoluble, e.g. Microcrystalline cellulose Certain liquid formulations do not require the specific addition of viscosity-enhancing agents, e.g. syrups, due to their inherent viscosity. 12/19/2017 Assefa A 82

83. f. Surface-active agents  Influence the stability of pharmaceutical liquid DF in several ways. To aid ‘wetting’ and dispersion of a hydrophobic API, preservative or antioxidant. Reduce interfacial tension between solid and liquid during manufacture or reconstitution of a suspension. Not all are suitable for oral administration. Examples include:  Oral: polysorbates (Tweens), sorbitan esters (Spans)  Parenteral: polysorbates, lecithin  External: sodium lauryl sulphate 12/19/2017 Assefa A 83

84. g. Sweetening Agents Natural sweeteners ◦ Sucrose ◦ Sucrose; soluble in water (vehicle)  Arguably the best taste/mouthfeel Sorbitol ◦ Sorbitol but lower sweetness intensity than sucrose (so you need more) Artificial sweeteners ◦ Much more intense sweeteners compared with sucrose ◦ Can impart a bitter or metallic after-taste (hence used in combination with natural sweeteners) Saccharin and it’s salts Aspartame  Examples: Saccharin and it’s salts Aspartame Sucralose – excellent sweetness, but relatively expensive 12/19/2017 Assefa A 84

85. h. Humectants Hygroscopic excipients used at ~5% in aqueous suspensions and emulsions for external application. Function: ◦ To retard evaporation of aqueous vehicle of dosage form. ◦ To prevent drying of the product after application to the skin. ◦ To prevent drying of product from the container after first opening. Examples include: Propylene glycol Glycerol PEG 12/19/2017 Assefa A 85

86. 12/19/2017 Assefa A 86 Routes of Drug Administration

87. A route of administration is the path by which a drug is taken into the body. ◦ the starting point for the drug’s introduction into the body appropriate administration route depends on ◦ the nature of the drug ◦ the nature and urgency of the medical condition. ◦ the patient’s age ◦ the patient’s condition, e.g. level of consciousness, etc. 12/19/2017 Assefa A 87

88. Routes of Drug Administration A drug administered via a certain route ◦ may be therapeutic ◦ or the same drug may be  ineffective  harmful  sometimes even fatal 12/19/2017 Assefa A 88

89. Routes of Drug Administration Some drugs are approved for use via more than one route and are manufactured in more than one dosage form appropriate for these routes. e.g. nitroglycerin  sublingual tablets  sublingual spray  ointment for transdermal application  intravenous solution for infusion 12/19/2017 Assefa A 89

90. Routes of Drug Administration classification 12/19/2017Abyou & Manaye Types of route of administration 1. Systemic route 2. Local route  skin and mucus membrane  Inhalation  vaginal A. Enteral -Oral -Buccal -Sublingual -Rectal B. Parenteral -Im -Iv -Sc

91. Routes of Drug Administration Enteral Involves administration of drugs via GIT Oral Advantages: ◦ Convenient, safe, no pain, easy to take. ◦ Cheap - no need to sterilize, compact, multi-dose bottles, automated machines. 12/19/2017Assefa A91

92. Routes of Drug Administration ◦ Oral dosage forms can be produced in large quantities. ◦ Variety of dosage forms available - fast release tablets, capsules, enteric coated, layered tablets, slow release tablets, suspensions, solutions, etc. Disadvantages ◦ Sometimes inefficient - low solubility drugs may suffer poor availability. ◦ First-pass effect (metabolism in liver) ◦ Not useful in vomiting and sever diarrhea. 12/19/2017 Assefa A 92

93. Routes of Drug Administration ◦ Irritant drugs can not be administered. ◦ Gastric acid and digestive enzymes may destroy some drugs. ◦ Food can affect drug absorption. ◦ Not useful for unconscious patient - Patient must be able to swallow the dosage forms. 12/19/2017 Assefa A 93

94. Routes of Drug Administration Buccal and Sublingual Smaller tablets are held in the mouth or under the tongue. Advantages ◦ First pass is by-passed ◦ Rapid absorption - Because of the good blood supply to the area of absorption. ◦ Drug stability - pH in mouth relatively neutral (stomach - acidic). Thus a drug may be more stable. 12/19/2017Assefa A94

95. Routes of Drug Administration Disadvantages ◦ Holding the dose in the mouth is inconvenient. ◦ The surface area available for absorption is very small. ◦ Usually more suitable for drugs with small doses. ◦ Drug taste may need to be masked. 12/19/2017Assefa A95

96. Routes of Drug Administration Rectal insertion of drug in to the rectum (suppository) Advantages: ◦ reduced first-pass effect. ◦ Useful for patients unable to take drugs orally  younger children.  unconscious patient ◦ Useful if the drug induces vomiting when administered orally or if the patient is already vomiting. 12/19/2017 Assefa A 96

97. Routes of Drug Administration Disadvantages: ◦ Rectal absorption is often irregular and incomplete. ◦ Many drugs cause irritation of the rectal mucosa. ◦ Not well accepted due to some discomfort. 12/19/2017 Assefa A 97

98. Routes of Drug Administration Parenteral administration of drugs by using injection. used for dugs that are poorly absorbed from the GI tract and for agents that are unstable in the GI tract.eg. Insulin. Intravenous (IV) Drugs may be given into a peripheral vein Advantages: ◦ Absorption phase is bypassed 12/19/2017Assefa A98

99. Routes of Drug Administration ◦ Drugs directly given to the vein, bioavailability is complete. ◦ Produce rapid action. ◦ Large volumes of drugs can be given. ◦ Certain irritating solutions can be given only by this route since the blood vessel walls are relatively insensitive, and the drug, if injected slowly, is greatly diluted by the blood. 12/19/2017 Assefa A 99

100. Routes of Drug Administration Disadvantages: ◦ It may be difficult to find a suitable vein. ◦ Drugs effect can not be halted if once the drug is injected. ◦ Expertise is needed to give injection. ◦ Drugs that precipitate blood constituents or hemolyze erythrocyte should not be given by this route. ◦ Expensive 12/19/2017 Assefa A 100

101. Routes of Drug Administration Subcutaneous (SC) Involves injection of a liquid into the fatty layer of tissue just below the dermis of the skin but above the muscle layer. Advantages: ◦ Can be given by patient, e.g. in the case of insulin. ◦ Absorption is usually complete and can be improved by massage or heat. 12/19/2017 Assefa A 101

102. Routes of Drug Administration Disadvantages: ◦ Can be painful. ◦ Finding suitable sites for repeat injection can be a problem. ◦ Irritant drugs can cause local tissue damage. ◦ slower absorption of the drug because only few blood vessels in this layer as compared to intramuscular injection. ◦ Maximum of 2 ml injection thus often small doses limit use. 12/19/2017 Assefa A 102

103. Routes of Drug Administration Intramuscular (IM) Injection of drugs to the gluteus maximus (Buttock), vastus laterallis (hip) or deltoid (arm). Advantages: Larger volume than SC can be given by IM. They may be easier to administer than IV injections. Provides more rapid absorption than via subcutaneous injection. 12/19/2017 Assefa A 103

104. Routes of Drug Administration ◦ A depot or sustained release effect is possible. ◦ Onset of action is faster than oral. ◦ It can be given in diarrhea or vomiting. Disadvantages: ◦ Trained personnel required for injections. ◦ Absorption is sometimes erratic. ◦ Pain at local site of injection. ◦ The volume of injection should not exceed 10ml. 12/19/2017 Assefa A 104

105. Routes of Drug Administration Intraarterial: Occasionally, a drug is injected directly in to the artery to localize its effect in a particular tissue or organ. e.g. In the treatment of liver tumors. ◦ Diagnostic agents are sometimes administered by this route. NB. Intra arterial injection requires a great care and should be reserved for experts. 12/19/2017 Assefa A 105

106. Routes of Drug Administration Intrathecal Administration of drugs directly in to the cerebrospinal fluid (CSF). The blood-brain barrier and the brain- cerebrospinal fluid barrier often precludes or slows the entrance of drugs in to the CNS. Therefore, when local and rapid effects of drugs on the meninges or cerebrospinal axis are desired as in spinal anesthesia, drugs are rapidly administered in to the spinal subarachnoid space. 12/19/2017 Assefa A 106

107. Local route Topical applied directly to the skin or the mucous membranes of the eye, ear, nose, or mouth. effect usually local, not systemic. Transdermal applied to the skin via physical delivery through a porous membrane. therapeutic effects felt systemically. 12/19/2017 Assefa A 107

108. Local route Inhalational The administration involves inhaling of a drug in gas or liquid form and it is absorbed through alveoli of the lungs. 12/19/2017Assefa A108

109. Other Routes Intra-nasal - small dose, avoid first pass Intra-arterial - cancer chemotherapy, localized delivery. Intraosseous route- in to bone marrow.  Others routes with limited systemic absorption but with local utility include: ocular aural vaginal urethral 12/19/2017 Assefa A 109

110. 12/19/2017 Assefa A 110