IDM - Pharmaceutical Formulation

1. What are Excipi- pharmacologically inactive substances formulated alongents ? side the drug in a medication (used to give the final dosage form). - Many excipients serve as the vehicle or medium for one or more APIs 2. Enteral (oral) Ad- Dosing of a drug for system wide-effects but delivery is ministration via the gastrointestinal tract. 3. Pros of Enter- Non-invasive al (oral) Adminis- - Can be modified for extended release tration - Convenient - Usually less expensive than other forms 4. Cons of Enter- Not appropriate for unconscious patients al (oral) Administration - Requires time for absorption and distribution - Patients may be unable to swallow - Absorption time is affected by food, drugs, stomach acid, and condition of gut - Metabolic processes in the GI tract may be problematic for some drugs - May cause patient discomfort/nausea - Sublingual/buccal tablets may not be taken correctly if patient is not appropriately instructed/counselled. 5. Oral Dosage forms Oral powders Tablets Capsules Liquids 1 / 20 6. Oral Powders: Bulk powders 7. Oral Powders: Di- Single doses of the powdered drug mixture individually vided powders enclosed in e.g., small sachets - intended to be taken in or with water e.g., Lemsip sachets 8. Oral Powders: Granules - agglomerates of powder mixes (usually of drug plus excipients) - can be bulk or divided - could be prepared by wet granulation or dry granulation - effervescent granules evolve CO2 when added to water 9. Oral tablets Solid dosage forms consisting of active ingredients and suitable pharmaceutical excipients. 10. Advantages of oral tablets ? - multi-dose preparations consisting of solid, loose, dry particles of varying degrees of fineness - contain one or more active ingredients - usually contain non-potent medicaments e.g., antacids - powder is then usually dispersed in water, effervescent powders, dissolved before taking. - Accuracy of dosage - Compactness - Portability - Blandness of taste - Ease of administration 11. Disadvantages - Limited dosage flexibility (certain strengths for each of oral tablets ? drug) - Complex formulation requirements, as tablets need to be hard & durable, but dissolve fast enough - poor wetting - slow dissolution - resist compression into dense compacts - Bitter tasting drugs, Drugs with an objectionable odour, drugs sensitive to oxygen or moisture may require encapsulation or entrapment prior to compression or the tablets may require coating. 12. 2 / 20 Excipients used Filler (or diluent) for Compressed tablets Binder Disintegrant Glidant Anti-adherent Lubricant Colourant Flavouring agent 13. Excipients used for Compressed tablets: Filler (or diluent) Lactose is the most common diluents - increases the size of the tablet - may not be necessary if the dose of the drug is high - Engineered xylitol has been recently suggested as a potential alternative excipient to produce tablets with improved physicomechanical and biopharmaceutical performance. 14. Excipients used e.g., starch paste for Compressed - usually added to promote granulation to ensure the free tablets: Binder flowing properties of the particles. - it is important to promote cohesive compacts during direct compression and ensure the tablet remains intact after compression. 15. Excipients used for Compressed tablets: Disintegrant E.g., starch - concentration as disintegrant is up to 10% - help the tablet to break down into small fragments, when it is ingested - helps the medicine to dissolve and be taken up by the body so that it can act more quickly 16. Excipients used - improves the flowability of the tablet granules or powder for Compressed by reducing the friction between particles tablets: Glidant - this prevents the formation of lumps 3 / 20 - most commonly used glidants is colloidal silica (Aerosil), 0.2% by weight 17. Excipients used Stop the powder from sticking to the equipment as the for Compressed tablet is being made. tablets: Anti-ad- e.g., magnesium stearate herent 18. Excipients used for Compressed tablets: Lubricant - Ensure the tablet has a smooth surface - Reduce the friction that occurs between the wall of the tablets and the walls of the die cavity when the tablet is ejected. 19. Excipients used - Colours added to help you recognise your tablet (provide for Comproduct identification) pressed tablets: - make it easier to take your medicine correctly Colourant 20. Excipients used for Compressed tablets: Flavouring agent - Used to improve a tablets taste - Usually limited to chewable tablets, tablets that are intended to dissolve in mouth, to mask unpleasant tasting API's. 21. Capsules Solid dosage forms in which the medicinal agent or excipient are enclosed in a small shell (often Gelatin). 22. What are Gelatin Sugar capsules com- Gelatin posed of ? Water 23. Advantages of capsules over liquid dosage forms ? - produced at a lower cost - it is more stable + longer half-life 24. Advantages of capsules over Solid dosage forms ? - more elegant - generally improved bioavailability - versatile = can carry liquid, semisolid or solid drugs - easily prepared extemporaneously - easily protected from light (opaque shell) 4 / 20 25. Liquid Oral dosage forms Solutions Emulsions Suspensions Syrups Elixirs Linctus Oral drops 26. Solutions Homogeneous liquid preparations for oral use containing one or more active ingredient dissolved in a suitable vehicle (mainly water). 27. What may a - Chemical degradation or Microbial contamination change in colour or cloudiness of a solution indicate ? 28. Advantages of Solutions ? - absorbed faster than solid dosage forms = cause less GI irritation - Phase separation is not a concern - more convenient means of drug administration to young children 29. Disadvantages of Solutions ? - susceptible to microbial contamination - possible hydrolysis of APIs in aqueous solution - taste of some drugs are more unpleasant in solution 30. What type of additives are used in the formulation of oral solutions ? - Buffers - Flavouring agents - Antioxidants - Preservatives 5 / 20 31. Emulsions Liquid preparations for oral use containing one or more active ingredient. - stabilised oil-in-water dispersions - solids may be suspended in oral emulsions - can be readily re-dispersed 32. Suspensions - liquid preparations for oral use containing one or more active ingredient suspended in a suitable vehicle. - sediment can be readily dispersed on shaking to give a uniform suspension which remains sufficiently stable to enable the correct dose to be delivered. - Useful for administering insoluble or poorly soluble drugs - taste of most drugs is less noticeable due to drug being less soluble in suspension. 33. Syrups - Liquid preparation in water = forms a simple syrup - addition of one or more active ingredients forms a medicated syrup. - used to mask the unpleasant taste of some APIs predominantly for administration in children - popular treatment for coughs as increased viscosity allows them increased contact time with the affected sites. 34. Elixirs - Liquid oral preparation that usually contains either potent or unpleasant tasting drugs. - has a clear formulation - generally contains a high proportion of sugar or other sweeting agent = to mask the offensive or nauseating tastes - non-aqueous solvents (alcohol, glycerine or propylene glycol) form a significant proportion of the vehicle used - solubilising agent could be used too 35. Linctus For the treatment of a cough: - used as a demulcent = forms a soothing film over a mucous membrane, relieving minor pain and inflammation - used as a expectorant = increased the production or hydration of secretions 6 / 20 - used a sedative - linctus is formulated to be as viscous solution containing sugars = sipped slowly, coating the throat in a undiluted form. 36. Oral drops Liquid preparations for oral use that are intended to be administered in small volumes with the aid of a suitable measuring device. Can be: - solutions - suspensions - emulsions 37. Parenteral administration Giving medication by a route other than the gastrointestinal system. 38. Advantages of Parenteral administration - drug does not pass though Intestinal tract - able to by pass first pass metabolism - provides fast drug action - eliminates factors that may affect absorption rates - can be used for unconscious patients who cannot swallow 39. Disadvantages of Parenteral administration - Invasive - may introduce bacteria into the system - Painful / frightening 40. Parenteral dosage forms Intravenous Intramuscular Subcutaneous intradermal Intra-articular Intra-arterial Intra-cardiac 7 / 20 Intraperitoneal Intrapleural Intravitreal Implants 41. Intravenous ad- Administration of a drug directly into a vein (IV). ministration 42. Advantages of - Drug does not pass through the Intestinal tract Intravenous ad- - Fast onset of action ministration - eliminates many of the factors that may affect absorption rates - immediately available as it is introduced directly to the blood stream. 43. Disadvantages of Intravenous administration - Invasive - may introduce bacteria in to the system - painful / frightening - recovery is more difficult if a medication error or adverse reaction occurs - requires a functioning cannula - cannula are prone to infection, tissuing 44. Intramuscular administration Involves a direct injection into a large muscle mass. - can be solutions or suspensions. 45. Advantages of Intramuscular administration - Drug does not pass through the intestinal tract - Fast on-set of action - Eliminates many of the factors that might affect absorption rates - Can be formulated for extended release 46. Disadvantages - Invasive of Intramuscular - may introduce bacteria in to the system administration - painful / frightening - Drug absorption may be erratic depending on the site 8 / 20 used, muscle mass of the patient and the amount of exercise performed by the patient. - May cause considerable bruising - Difficult to reverse the drug action once it has been injected - It is not appropriate for patient with decreased muscle mass or bleeding problem. Injection fibrosis may occur if injections are delivered with great frequency or with improper technique. 47. Subcutaneous administration Injecting drugs or medication just below the skin. - Highly effective in administering vaccines and medication such as insulin. 48. Advantages of Subcutaneous administration - Drug does not pass through the intestinal tract - Patient can be taught to self-administer 49. Disadvantages of Subcutaneous administration - Invasive - may introduce bacteria in to the system - Limited volume of medication can be injected - May be difficult for patients with thin or frail skin - Rate of absorption is slower than the IV or IM routes 50. Intradermal Administration Inserted in the top layers of the skin - not as deep as SC injection - often used for allergen testing 51. Intra-articular Administration Injection of drug into the joints e.g., the knee 52. Intra-arterial Ad- An injection of a drug directly into an artery ministration - delivers drug directly to desired location = decreases the side effects to other parts of the body. - Cancer chemotherapy drugs are sometimes administered by this method, extreme caution should be used because these drugs are toxic. 53. Intra-cardiac Ad- Injection of drugs directly into the heart muscles. ministration - used only in extreme life-threatening emergencies 9 / 20 54. Intraperitoneal Administration An injection into the peritoneal or abdominal cavity - used to administer antibiotics needed to treat infections in the abdominal cavity, such as peritonitis resulting from a ruptured appendix. 55. Intrapleural Administration An injection into the pleural or sac surrounding the lungs. - this is to eliminate or prevent excessive amounts of fluid from building up in the pleural sac surrounding the lungs. 56. Intravitreal Administration a injection into the vitreous of the eye. - used to place medicines inside the eye, near the retina. 57. Implants A medication pump, e.g., insulin pump, or a medical device that is inserted into the body either permanently or for a prescribes amount of time and is designed to provide continuous administration of a drug over a predetermined amount of time. 58. Topical (local) application - Brings drug formulation into contact with the skin. 59. Topical agents Semisolids Mouthwashes, Throat sprays and Gargles Dusting Powders Poultice 60. Advantages of Topical (local) application - Application can be direct to site of action - Some product can produce a systemic effect by having the drug diffuse through the skin and into the bloodstream. 61. Disadvantages - Skin acts as a natural barrier that will affect the rate and of Topical (local) amount of penetration application - Usually the concentration needed to provide a therapeutic effect is difficult to determine. 62. Describe Semisolid dosage forms ? - products of semisolid consistency to be applied to skin or accessible mucous membranes for therapeutic, protection or cosmetic function. 10 / 20 - they are used for topical applications and intended for localised drug delivery. - Common sites of application = skin, eyes, nose, vagina, urethral membrane and rectum. 63. Advantages of - flexible dosing Semisolid - suitability for local and systemic drug delivery dosage forms ? 64. Disadvantages - less stability of Semisolid - less contamination dosage forms ? - less dosing errors 65. Physiochemical - Smooth texture properties of - Non-dehydrating Semisolids - Non-gritty - Pharmaceutically elegant - Non-greasy and non-staining - Not hygroscopic 66. Physiological properties of Semisolids Non-irritating Low sensitization index Do not alter with normal skin function/ membrane Miscible with skin secretion 67. Application properties of Semisolids - Easy to apply / wash off - Efficient drug release 68. Semisolid Dosage forms Ointments Creams Pastes Gels Plasters Liniments 11 / 20 Lotions Collodion Paints 69. Ointments Homogenous, translucent, viscous semisolid preparations intended for external applications. - useful in any condition characterised by dry skin e.g., atopic dermatitis - Ointments soften and do not melt upon application to the skin Classification: - Epidermic = antiseptics / protectives - Endodermic = emollients / moisturising - Diadermic = systemic Ointments can be medicated or non medicated = used for protective and lubricating effects. - base is usually anhydrous and immiscible with skin secretions 70. Creams Semisolid emulsions (mixtures of oil and water) - less greasy than ointments - components are usually absorbed into the skin - either oil-in-water (O/W) or water-in-oil (W/O) emulsions - O/W emulsions = rub into skin & washed off easily - W/O emulsions = greasier 71. Cold creams Semisolid W/O (Water in oil) emulsion - used as emollient 72. Eucerin cream W/O emulsion of Petrolatum, Mineral Oil, Mineral Wax, Wool Wax, Alcohol and Bronopol . 73. Vanishing cream O/W emulsion with high content of water and humectant (glycerin or propylene glycol) to retard surface evaporation. - contains 15% stearic acid as an internal phase 12 / 20 74. Compare Ointments and Creams ? Ointment = Oleaginous base, low water content = less then 20% - more greasy (volatiles) Cream = Greater water content, more than 20% # - less volatiles 75. Pastes Semisolid dosage forms that contain one or more drug incorporated in a base with large proportions of finely dispersed powders - very difficult to remove - they are useful for dry surfaces - Pastes absorb secretions and protect skin - can neutralise certain noxious chemicals before they ever reach the skin. E.g., Zinc oxide paste - containing 25% zinc oxide in starch % white petrolatum - can form a unbroken relatively water-impermeable film - fil is opaque and can be used as an effective sun block - they are less greasy because of the absorption of the fluid hydrocarbon fraction to the particulates. 76. Gels - dispersion of small or large molecules in an aqueous liquid vehicle - semi-colloids which liquefy on contact with skin Used for = medication, lubrication and carrier for spermicidal agents to be used intra-vaginally with a diaphragm. - common form for acne preparations e.g., Acnederm Single phase gels = Gelling agent is uniformly distributed throughout the liquid, no apparent boundaries exist between them. Two-Phase gels = consist of floccules of small, distinct particles. Hydrogels = hydrophilic polymeric gelling agents in water. Organogels = Thermoplastic thermoreversible) materials 13 / 20 containing liquid organic phase entrapped in 3-dimensionally cross-linked network of gelling agents. 77. Plasters Solid or semisolid adhesive masses spread onto backing paper or fabric for a local effect. - usually applied to the skin to bring medication in close prolonged contact with the skin surface. E.g., salicylic acid plasters are used on the toes for the removal of corns. 78. What are Plas- provide protection and mechanical support ters used to do ? - Furnish an occlusive and macerating action - Bring medication into close contact with the surface of the skin. 79. Liniments - fluid, semi-fluid, or semi-solid preparations for application to the skin, may be alcoholic or oily solutions or emulsions - it is massaged into the skin and should not be applied to broken skin. 80. Lotions Fluid preparations (aqueous) for external application without friction. - either dabbed on the skin or - applied on a suitable dressing and covered with waterproof dressing to reduce evaportion. 81. Paints Liquids for application to skin or mucous membranes. - Skin paints contain volatile solvent that evaporates quickly and leaves a dry resinous film of medicament - Throat paints are more viscous due to a high content of glycerol, designed to prolong contact of the medicament with the affected site. 82. Collodion Solution of nitrocellulose in ether or acetone, sometimes with the addition of alcohols. Generic name = Pyroxylin solution 14 / 20 - it is highly flammable - as the solvent evaporates, it dries to a celluloid-like film - used to seal minor injuries (artificial skin) - used to bring the API into contact with the skin and hold it in place Compound Wart Remover = consists of acetic acid and salicylic acid in an acetone collodion base used in treatment of warts by keratolysis. 83. Mouthwashes, Throat sprays, Gargles - used to target a local site of action (the mouth or throat) - may contain antiseptics, anaesthetics, deodorants, and flavourings - used to relieve minor sore throat pain, to improve bad breath, etc. 84. Dusting powders Finely divided insoluble powder containing ingredients such as talc, zinc oxide, or starch as its base - API can be added to give the powder therapeutic activity (e.g., as an antiseptic or antifungal) - some can absorb moisture (e.g., an astringent) = discourages bacterial growth. - Other used for their lubricant properties 85. Poultice - Paste-like preparations used externally to reduce pain and inflammation because they retain heat well. - After heating, the preparation is spread thickly on a dressing and applied as hot as the patient can bear, to the affected area. 86. Advantages of Inhalation administration - very rapid absorption to the huge surface area of the respiratory endothelium - Bronchodilators and inhaled steroids can be targeted to lungs with low levels of systemic absorption. 87. Disadvantages of Inhalation administration - Bioavailability depends on patient's inhaler techniques and the size of drug particles generated by the delivery technique - Inhaled corticosteroids can cause moth and tongue soreness, hoarseness of voice and oral thrush. 15 / 20 88. Inhalation dosage forms - Metered dose inhaler - Nebuliser or atomiser 89. Metered dose in- - solutions, suspensions or emulsion of drugs in a mixture haler of inert propellants held under pressure in an aerosol dispenser. - commonly used to treat asthma and other respiratory problems 90. Nebuliser (atom- - A device used to administer medication to people in iser) forms of a liquid mist to the airways. - commonly used in treating asthma, and other respiratory diseases. - reserved only for serious cases of respiratory disease, or severe attacks = more expensive, more side effects. 91. Transdermal route of administration Delivery of drug across the top of the skin for percutaneous absorption to facilitate a systemic effect. - for continuous slow absorption of various medications 92. Advantages: Transdermal route - skin assists in controlling the rates of absorption and delivery to bloodstream - Drug does not pass through intestinal tract 93. Disadvantages: Transdermal route May cause skin irritation or reactions 94. Transdermal dosage forms Transdermal patches = applied to the skin and releases the drug over a period of time. - drugs pass through the skin and enter the general circulation - first commercially available = scopolamine , for motion sickness 95. Advantages of Transdermal patches - avoiding hepatic first-pass metabolism - enhanced therapeutic efficacy - minimum side effects - improve patient compliance 16 / 20 - abrupt termination of drug by wiping the drug off the skin - allowing high local concentration 96. Disadvantages of Transdermal patches - Irritation - side effects due to systemic drug absorption - may wipe away easily 97. Rectal administration Drugs are inserted through the anus into the rectum. - it is intended to melt or dissolve and release the medication after it is inserted. - medication is absorbed through the rectal mucosa to provide a systemic effect or it may exert a topical effect. 98. Advantages of Rectal administration - Good absorption - the haemorrhoidal veins drain directly into the inferior vena cava, avoiding hepatic first pass metabolism. 99. Disadvantages of Rectal administration - May not suitable after rectal or anal surgery - Some patients dislike suppositories 100. Rectal dosage forms Rectal suppositories Enemas 101. Rectal supposi- - small solid medicated masses, usually cone-shaped, tories that are inserted into the rectum where it melts at body temperature. - produce local or systemic effects 102. Enemas Drug is suspended in a solution and infused into the rectum and colon via the anus. - Evacuant enema = used as a bowl stimulant to treat constipation , requires warming - Retention enema = no warming needed, may exert local or systemic effect. 103. Vaginal adminis- Tablets or suppositories intended for insertion into the tration vaginal canal, designed to melt or dissolve and release 17 / 20 the medication. Include creams, ointments, gels, solutions and foams. 104. Vaginal Dosage forms Suppositories (pessaries) Vaginal ring IUD 105. Vaginal Sup- produce a local antimicrobial effect positories (Pes- Moulded Pessaries = cone shaped saries) Compressed Pessaries = Prepared by compression Vaginal capsules = soft Gelatin oral capsules differing only in size and shape 106. Vaginal ring Doughnut shaped polymeric drug delivery device designed to provide controlled release of drugs in the vagina over extended periods of time. 107. Intrauterine device (IUD) contraceptive device inserted into the uterus that prevents implantation of a fertilized egg - constructed of copper and plastic, which are inserted into the uterus. 108. Ocular adminis- Solutions are instilled into the eye. tration route Ocular inserts = solid devices that are placed in the eye and release a drug at a constant rate, minimising side effects due to rapid absorption. 109. Otic administra- Include solutions or suspensions that are administered tion route into the ear canal and contain analgesics, antibiotics, and anti-inflammatory agents. 110. Nasal administration route Solutions are administered to the nasal passages in the form of drops or sprays and may be either suspensions or emulsion. 111. Advantages of Ocular, Otic, Nasal routes of Administration Direct application 18 / 20 112. Disadvantages of Ocular - Must be sterile preparations free of any particulate matter that may irritate the eye - care should be taken to avoid touching the eye with the tip of the dropper or ointment tube - Ocular insets = hard to insert properly, insert must be removed from the eye after the drug is released 113. Ophthalmic dosage forms eye drops, ointments and gels 114. Otic dosage forms Ear drops 115. Nasal dosage forms Nasal drops and sprays 116. Biopharmaceu- High Permeability, High Solubility tics Classification System: Class 1 117. Biopharmaceu- High Permeability, Low Solubility tics Classification System: Class 2 118. Biopharmaceu- Low Permeability, High Solubility tics Classification System: Class 3 119. Biopharmaceu- Low Permeability, Low Solubility tics Classification System: Class 4 120. Primary manufacturing - the API is made achieved by synthesis, biosynthesis or fermentation. 121. 19 / 20 Secondary Man- Active ingredient is mixed with other agents to create the ufacturting physical form required for delivery of the drug e.g., tablets, liquids or creams. 20 / 20