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1. Semisolid Dosage Forms MA (BSC): Semisolid DF

2. MA (BSC): Semisolid DF Outline Introduction to skin structure Ointments Pastes Creams Gels

3. 1 . INTRODUCTION TO SKIN MA (BSC): Semisolid DF Outermost horny covering layer of body Largest organ SKIN COMPOSTION

4. MA (BSC): Semisolid DF Dermatologicals Drug Absorption Topicals Vs Transdermals (based on intended effect) 1. Topical Target site is the skin D ermatologicals designed to treat dermal disorders  2. Transdermal delivery systems D esigned to deliver drugs through the skin Percutaneous absorption to the general circulation Systemic effects Target site other than the skin

5. MA (BSC): Semisolid DF Percutaneous Absorption Transepidermal Transcellular (for hydrophilic drugs) Intercellular (for lipophilic drugs) Transappendageal Hair follicles, s ebaceous & s weat glands Minor importance For ions and large polar molecules

6. Percutaneous… MA (BSC): Semisolid DF Steps involved in Percutaneous absorption Why transdermal drug delivery?

7. MA (BSC): Semisolid DF Percutaneous… Factors affecting percutaneous absorption Skin factors Thickness of stratum corneum ( site of application, age) Intactness of skin Time of contact Blood flow (drugs, skin metablisim, hydration) Drug factors Concentration Partition coefficient Molecular weight & particle size

8. MA (BSC): Semisolid DF Percutaneous… Nature of vehicle Spreadability of vehicle Mixing with the sebum Hydration of the skin Altering skin permeability

9. MA (BSC): Semisolid DF Introduction to Semisolids Semisolids DFs that have properties in between solid and liquid dosage forms Possess rheological properties that help easy application and retention for prolonged time Applied topically to the skin or on the surface of the eye, nasally, vaginally, or rectally for local and/or systemic effects Different forms : Ointment , cream , paste , gels Ensuring uniformity of the distribution in the mix and potency uniformity depends on the control of particle size Ability to readily incorporate variety of hydrophilic and hydrophobic drugs

10. MA (BSC): Semisolid DF Desired Properties of Dermatologicals Should be non- irritating to the skin Should release the medicaments readily Should not interfere with normal function of the skin Should be easily spread on the skin (affected area) Should adhere on to the applied area Should be suitable for application by the patient

11. OINTMENTS Semisolid dosage forms (usually greasy ) containing medicaments dissolved or dispersed in a suitable base of mineral, vegetable, or synthetic origin Anhydrous MA (BSC): Semisolid DF 1. Medicated ointments T herapeutic effect, according to their use c lassified as Acne treatment , k eratolytics , a ntifungal , a ntibiotics , a ntipruritic , a nti- inflammatory agents 2. Non- medicated Physical Effects Emollient , p rotectant , l ubricant Vehicles in the preparation of medicated ointments Commonly referred to as ointment bases

12. MA (BSC): Semisolid DF 17 Ointment Bases Part of ointment which serve as a carrier/vehicle for the medicament Traditonally, the ointment base may be waxes, fats and oils Qualities of an ideal ointment base Stable , i nert Nonirritating, nonsensitizing Smooth and free from grittiness Able to release incorporated medication

13. MA (BSC): Semisolid DF 18 Ointment Bases… Types: Hydrocarbon (oleaginous) Bases Absorption Bases Water Removable/miscible Bases Water- soluble Bases

14. MA (BSC): Semisolid DF 20 1. Hydrocarbon Bases Anhydrous , a bsorb very little water , < 5% Hydrophobic , g reasy vehicles , f orm occlusive film emollient Excellent retention on the skin , u se for the treatment of dry scalp Should not be applied to exuding areas due to poor water uptake capacity  cause maceration Do not “dry out” or change noticeably upon aging Difficult to wash and spread on wet skin Absorption by skin ?

15. Hydrocarbon Bases… Examples…. A . Hard paraffin Mixture of solid saturated hydrocarbons A colorless or white, odorless,translucent, wax-like substance that feels slightly greasy MP = 47– 65 C Used to enhance stiffness of ointment bases 9 23 MA (BSC): Semisolid DF CnH2n+2

16. Hydrocarbon Bases… Examples: B . Soft paraffin (Petrolatum, Vaseline) Mixture of semi- solid hydrocarbons Two types : Yellow soft paraffin (for colored ingredients) White soft paraffin (for colorless; white or pale ingredients) Have MP range of 38- 60 C MA (BSC): Semisolid DF 22

17. Hydrocarbon Bases… Examples… c. Liquid paraffin (mineral oil) Mixture of liquid hydrocarbons On long storage  oxidation ?? Use L evigating agent Formulated with white/yellow soft paraffin to achieve required viscosity MA (BSC): Semisolid DF 24 Yellow / white Ointment, USP 50 g 950 g Yellow / white wax: Petrolatum:

18. MA (BSC): Semisolid DF 26 Hydrocarbon Bases… Restricts the loss of moisture hence, keeps the skin soft Sticky hence ensures prolonged contact Almost inert hence very few incompatibilities and little tendency of rancidity Readily available and cheap May lead to water logging followed by maceration of the skin Retains body heat, which may produce discomfort Rubbing onto the surface and removal after treatment difficult Are sticky, hence makes application unpleasant Water absorption capacity is very low Advantages Disadvantages

19. MA (BSC): Semisolid DF 27 2. Absorption Bases Anhydrous or hydrous bases that can absorb considerable amounts of water or aqueous solutions Occlusive but not much as HC bases , d ifficult to remove from site of application Used to incorporate aqueous solutions of drugs into oleaginous bases Two types: Non- e mulsion bases 2) E mulsified (W/O emulsions) bases 1 . Non- emulsified bases: Are anhydrous and greasy Absorb water & aqueous solutions form W/O emulsions Less occlusive than HCs but are good emollients Easier to spread than HC bases Commonly composed of one or more paraffins and a sterol- based emulsifying agent (wool fat, wool alcohols, bees wax)

20. Absorption Bases… 1 . Non- emulsified bases… A) Wool fat (anhydrous lanolin); refined wool fat Wax- like material that is derived from sheep’s wool C ontain no more than 0.25% of water , t oo sticky to use alone Mixed with paraffins or vegetable oils to produce a base that can absorb approximately 2X its own weight of water w/o emulsion They are used 5-10% W/W MA (BSC): Semisolid DF 29 Hard paraffin Cetostearyl alcoho l Wool fat Soft paraffin 50g 50g 50g 850g Simple ointment B.P Use: as emollient and base for other ingredients

21. Absorption Bases… a. Non- emulsified bases… B) Beeswax : Included in some ointment bases to increase water absorbing power ?? Combined with paraffins to produce non- emulsified bases MA (BSC): Semisolid DF 32

22. MA (BSC): Semisolid DF 31 Absorption Bases… 1. Non- emulsified bases… C) Wool alcohols (lanolin alcohol) Added to mixtures of paraffins (hard, soft or liquid) to produce the required consistency Inclusion of 5% w/w wool alcohols 300% increase in the concentration of water that may be incorporated into paraffin bases

23. MA (BSC): Semisolid DF 33 Absorption Bases… Non- emulsified bases… 4) Hydrophilic Petrolatum, USP A bsorb water, with the formation of a water-in- oil emulsion U seful to incorporate extemporaneously a water- soluble drug into an oleaginous base Composed of: Cholesterol Stearyl Alcohol White Wax and White Petrolatum 30 g 30 g 80 g 860 g Commercial products, Aquaphor and Aquabase , variations of hydrophilic petrolatum, absorb up to 3X their weight in water

24. MA (BSC): Semisolid DF 34 Absorption Bases… b. Water- in- oil Emulsions (emulsion bases) Already W/O emulsion  permit incorporation of small additional quantities of aqueous solution Insoluble in water, not water washable, contain water (limited) E mollient, occlusive, greasy Hydrous wool fat (lanolin) Prepared from wool fat (70%) and water (30%) Used alone as an emollient and As an ingredient of several B.P ointments such a s c alamine and coal tar ointment , m ethylsalicylate ointment

25. MA (BSC): Semisolid DF 36 Absorption Bases… Water- in- oil Emulsions… Cold cream, USP Cetyl esters wax , White wax, Mineral Oil, Sodium Borate and Water Is there any emulsifying Agent, and how could they form W/O emulsion ?

26. MA (BSC): Semisolid DF 37 3. Water- miscible (Water- removable) bases Are O/W emulsions or form O/W emulsions Can be applied to the scalp and other hairy regions British Pharmacopoeia describes three miscible/removable bases: Emulsifying ointment B.P – anionic Cetrimide emulsifying ointment B.P – Cationic Cetomacrogol emulsifying B.P- Non- ionic water-

27. MA (BSC): Semisolid DF 38 3. Water- miscible… Each of these contains 20% liquid paraffin, 50% white soft paraffin; and 30% anionic, cationic or non- ionic emulsifying wax Able to accommodate large volumes of water, e.g., aqueous solutions of drug, excess moisture at the site of application and exudates from lesions e-wax vs b-wax

28. MA (BSC): Semisolid DF 39 3. Water- miscible… Reduced interference with skin function (are not occlusive ) Good contact with skin because of their surfactant content High cosmetic acceptability (aesthetically pleasing) Easy removal from the hair, skin and cloth Also called ‘ water- washable ’ bases They can absorb serous discharges Also called creams

29. MA (BSC): Semisolid DF 40 3. Water- miscible… Cetomacrogol Emulsifying Ointment BP (Non- Ionic Emulsifying Ointment) Ingredients White Soft Paraffin BP Cetomacrogol Emulsifying Wax BP Liquid Paraffin BP 500 g 300 g 200 g Use: Used as vehicle with easy miscibility with exudates, high cosmetic acceptability and, because of the emulsifying properties, easy removal from the scalp

30. MA (BSC): Semisolid DF 41 3. Water- miscible… Cetrimide Emulsifying Ointment BP (Cationic Emulsifying Ointment) Ingredients Cetrimide Emulsifying Wax BP White Soft Paraffin BP Liquid Paraffin BP 300 g 500 g 200 g Use: Used as an antiseptic ointment

31. MA (BSC): Semisolid DF 42 3. Water- miscible… Emulsifying Ointment BP (Anionic Emulsifying Ointment) Ingredients Emulsifying Wax BP White Soft Paraffin BP Liquid Paraffin BP 300 g 500 g 200 g Use: A water-miscible ointment base, particularly useful for application to the scalp

32. MA (BSC): Semisolid DF 43 Emulsifying waxes Anionic emulsifying wax: Cetostearyl alcohol 90 g Sodium lauryl sulphate 10 g Purified water 4 ml Non- ionic emulsifying wax = Cetomacrogol Emulsifying Wax BP Cetostearyl alcohol Cetomacrogol 1000 800 g 200 g Cationic emulsifying wax = Cetrimide Emulsifying Wax BP Cetostearyl alcohol Cetrimide 900 g 100 g

33. MA (BSC): Semisolid DF 44 Exampl e Hydrophilic Ointment, USP Methylparaben 0.25 Propylparaben 0.15 Sodium lauryl sulphate 10.00 Propylene glycol 120.00 Stearyl alcohol 250.00 White petrolatum 250.00 Purified water 370.00

34. MA (BSC): Semisolid DF 45 4. Water soluble bases Readily miscible with tissue exudates , Easily removed from the skin , Are called ‘Greaseless’ bases Do not hydrolyze, rancidify or support microbial growth Developed from the Macrogols (PEGs), compounds with general formula: CH 2 OH.(CH 2 OCH 2 ) n .CH 2 OH Predominantly prepared using different molecular weight PEGs to produce the required ointment consistency Macrogols with MW <600 are viscous liquids; Macrogols >1000 are waxy solids and those with molecular weight in between are semisolids

35. MA (BSC): Semisolid DF 47 4. Water soluble bases… Compatible with many dermatological medicaments Limited uptake of water (<5%) Usually reserved for incorporation of solid drugs However, may incorporate up to 25% of an aqueous solution if portion of PEG is replaced with stearyl alcohol Good solvent properties,

36. MA (BSC): Semisolid DF 48 4. Water soluble bases… Polyethylene Glycol Ointment, USP PEG 3350 PEG 400 400g 600g If 6- 25% of aqueous solution is to be incorporated, the USP allows substitution of 50 g of the PEG 3350 with an equal amount of stearyl alcohol in order to render the final product firmer, more viscous

37. MA (BSC): Semisolid DF 49 Selection of Base Careful assessment of different factors: Desired release rate of the drug Desirability of topical or percutaneous drug absorption Desirability of occlusion of moisture Stability of the drug in the ointment base Effect, if any, of the drug on the consistency or features of the ointment base other Desire for easy removal by washing with water Characteristics of the surface to which it is applied

38. MA (BSC): Semisolid DF 50 Other ingredients of ointments Vegetable oils: May be used either to replace mineral oil or May be added to hydrophobic or absorption bases to increase emollient properties and for softening effects Examples: Arachis, castor, coconut and olive oils Disadvantages : Prone to oxidation requiring inclusion of antioxidants, stabilizers which may cause sensitization in some patients May not be consistent in composition

39. MA (BSC): Semisolid DF 51 Other ingredients… Organic esters (Synthetic esters of fatty acids) Used partly to replace a mineral oil (vegetable oil) to enhance the spreadability and To enhance drug dissolution within the ointment base Esters such as isopropyl myristate are more consistent in composition than the vegetable oils and are more resistant to oxidation

40. MA (BSC): Semisolid DF 52 Other ingredients… Higher fatty alcohols Examples: Cetyl, stearyl and cetostearyl alcohols Used in ointment bases because: They are emollients but are not greasy Facilitate incorporation of water  White soft paraffin containing 5% of Cetyl alcohol absorbs 40- 50% of its weight of water and even more if 10% of wool fat is also incorporated. They assist absorption of water by macrogol bases They are readily absorbed by the skin and do not rancidify

41. MA (BSC): Semisolid DF 53 Other ingredients… Antioxidants Prevent/reduce oxidation of either the non- aqueous components of the ointment base and/or the therapeutic agent antioxidants: e.g., Butylated hydroxyanisole hydroxytolnene (BHT), and ethyl, propyl or (BHA), dodecyl Lipophilic Butylated gallates Hydrophilic sulphite antioxidants: e.g., sodium metabisulphite, sodium Chelating agents such as EDTA may be included Must be compatible with medicaments

42. MA (BSC): Semisolid DF 54 Other ingredients… Preservatives May not be required in anhydrous ointments Ointment with an aqueous component requires effective antimicrobial agents Preservatives used in formulations for external use include: chlorocresol; benzoic acid and and propylparaben; benzyl salts; alcohol; phenol and methylparaben phenoxyethanol

43. Compounding of Ointments MA (BSC): Semisolid DF 55

44. MA (BSC): Semisolid DF 57 Preparation… Two general methods of preparation: Fusion Incorporation The method used for a particular preparation depends primarily up on the nature of ingredients.

45. MA (BSC): Semisolid DF 58 1. Fusion Method Involves melting together of the bases over a water bath before incorporating other ingredients The ointment base may include a mixture of waxes, fats and oils of which some are solids like hard paraffin , beeswax , cetostearyl alcohol Also used when drug is more soluble in melted base, non volatile and thermostable

46. MA (BSC): Semisolid DF 59 Fusion… Procedures Make excess/overage as transference losses will always occur When base contains several ingredients of different melting points   F irst melt the constituent of high melting point As the first base cools, add the ingredients with decreasing melting points at the respective melting points Heat- labile and volatile components are added last when temperature of the mixture is low enough Caution ; Do not overheat! Those components not melted are generally added to the congealing mixture as it is being cooled and stirred

47. MA (BSC): Semisolid DF 60 Fusion… Procedures… 3. Stir continuously to ensure a homogeneous mix before leaving to set (congeal) Strategies - S tir gently - avoid i ncorporating excess air avoid l ocalized cooling & a lumpy product How could l ocalized cooling occurred ?

48. Fusion… On a small scale; porcelain dish or glass beaker On a large scale; large steam jacketed kettles Once congealed, the ointment may be passed through ointment mill (in large- scale) or rubbed with spatula or in a mortar (in small scale) to ensure a uniform texture MA (BSC): Semisolid DF 61

49. MA (BSC): Semisolid DF 64 Fusion… Incorporation of powders/ solids a. Soluble solids Added to the molten fatty bases at the lowest possible temperature Alternatively, if using a pre- prepared base, soluble solids may be incorporated using the method employed for insoluble solids b. Insoluble solids Incorporated using an ointment tile and spatula If there is more than one powder to be added, these should be mixed in a mortar using the ‘ doubling- up ’ method Fine powders may be triturated into the finished ointment on an ointment tile or a small amount of powder may be levigated with some molten ointment base on a tile and the resulting mixture returned to the remaining molten mass and stirred Coarse powders should be levigated with portion of the molten base on a tile

50. MA (BSC): Semisolid DF 67 Fusion… Incorporation of liquids a. Non- volatile, miscible liquids Mixed with the molten fat in the evaporating basin Alternatively, if a pre- prepared base is used, incorporate as for volatile or immiscible liquids b. Volatile or immiscible liquids Triturated with the ointment on an ointment tile Very small amount of the ointment should be placed on the tile and a ‘ well ’ made in the centre Small quantities of liquid should be gently folded in to avoid splashing

51. MA (BSC): Semisolid DF 69 Incorporation (Trituration) Method Components of the ointment are mixed together by various means until a uniform preparation has been attained Used when all ingredients can be triturated The ingredients should have to be in their finest state Apparatus T ile and spatula S patulation method : larger spatula with a smaller spatula S tainless steel : flexible, flat, long and broad ) H ard rubber : phenol, salicylic acid, mercury salts, iodine Mortar & Pestle M echanical ointment roller mills and large steam jacketed vessels

52. Incorporation … Geometric dilution of drug with base Levigate with small amount of base Mix well Add second part Mix well and continue geometric dilution Mix well until homogeneous MA (BSC): Semisolid DF 77 a. Incorporation of solids

53. MA (BSC): Semisolid DF 78 Incorporation … b. Incorporation of liquids Liquid substances or solutions of drugs are added only after due consideration of the ointment nature In case of hydrophobic base if an aqueous solution is to be added, a portion of the hydrophobic base may be replaced by a hydrophilic base Preparation techinques A very small amount of the ointment should be placed on the glass tile and a ‘ well ’ made in the centre Small quantities of liquid should be gently folded in to avoid splashing Volatile ingredients (e.g., coal tar) should not be weighed until immediately before use and the beaker in which it has been weighed should be covered with a watch glass

54. Filling of Ointments MA (BSC): Semisolid DF 80

55. MA (BSC): Semisolid DF 56 Preparation of Ointments .... A well- made ointment is: a. Uniform throughout b. Free from grittiness c . Method of preparation must satisfy these criteria Difficulties in preparation of ointments 1. C hemical reaction between steel spatula and some reactive ingredients Solution: Use wooden spatula or hard rubber spatula 2. Incorporation of aqueous solution into hydrocarbon base Solution: addition of wool fat, higher fatty alcohols 3. Incorporation of drugs (e.g., antibiotics) sensitive to hydrolysis Solution: Use hydrocarbon base

56. Packaging and storage of ointments Ointments are usually packaged either in jars or tubes Jars: may be made of glass (uncolored, colored or opaque) - Can be made of plastic Tubes: are made of tin or plastic ( collapsible tube) Jars may be filled on a small scale by means of a flexible spatula, forcing a weighed amount of ointment down and along the sides of the jar to avoid entrapment of air MA (BSC): Semisolid DF 82

57. Packaging and storage… Tube- filled ointments predominate jar-filled ointments because they are more convenient for the patient Ointments in tubes are less exposed to air and potential contaminants & are comfortable to patients more stable and remain efficacious for longer periods Ointments must be stored at temperatures below 30 C to prevent softening and liquefying of the base   sedimentation of solid components MA (BSC): Semisolid DF 83

58. MA (BSC): Semisolid DF 84 Examples R x Simple Ointment BP Cetostearyl Alcohol BP Hard Paraffin BP Wool Fat BP White/Yellow Soft Paraffin BP Mitte: 30 g Sig. Mdu 50 g 50 g 50 g 850 g Overage must be produced in order to dispense the required amount calculate for 40g Appropriate method – fusion

59. MA (BSC): Semisolid DF 85 Examples… MPs of ingredients Cetostearyl Alcohol BP: 49–56°C Hard Paraffin BP: 50–61°C White/Yellow Soft Paraffin BP: 38–56°C Wool Fat BP: 38–44°C Weigh the calculated amounts using waxed paper Place the h ard p araffin into an evaporating dish and melt over a water bath

60. MA (BSC): Semisolid DF 86 Examples… Remove from heat and add other ingredients in descending order of MP Return to the heat if necessary  Stir until cold, Weigh 30 g and pack into a collapsible tube or amber glass jar

61. MA (BSC): Semisolid DF 87 Examples… Label and dispense Labeling Simple Ointment BP 30 g Apply as directed For external use only Do not use after (3 months) Name ----------------- Date of dispensing --------------

62. MA (BSC): Semisolid DF 88 Examples… Compound Benzoic Acid Ointment BP (Whitfield's Ointment) Ingredients Emulsifying Ointment BP Benzoic Acid BP Salicylic Acid BP Sig. Apply twice a day. Use: Antifungal and antibacterial Quantities 910 g 60 g 30 g Appropriate method: incorporate the powders into the base on a tile after mixing them in a mortar

63. MA (BSC): Semisolid DF 89 Examples… Salicylic acid ointment 5% MF 5 g 95 g Formulation Salicylic acid Petrolatum Send 50g Sig. apply as directed Preparation: Grind the salicylic acid. Triturate the salicylic acid with an equal amount of petrolatum. Add the rest of the petrolatum gradually and mix until homogeneous. Use: keratolytic and hydrating properties; used for the treatment of hyperkeratotic conditions and for psoriasis

64. Examples… Dithranol ointment Formulation M F Dithranol 1 g Salicylic acid 0.5 g Emulsifying ointment 98.5 g Preparation: Mix the salicylic acid and the dithranol. Triturate the mixture carefully with a portion of emulsifying ointment and mix until homogeneous. Add the rest of the emulsifying ointment gradually and mix after each addition until homogeneous Use : treatment of psoriasis Precaution : irritant; avoid contact skin and the eyes. MA (BSC): Semisolid DF

65. MA (BSC): Semisolid DF 91 Examples… Rx Zinc Oxide Ointment BP Zinc Oxide BP Simple Ointment BP Sig. tid Mitte: 20 g ** This ointment is used eczematic conditions 150 g 850 g for nappy and urinary rash and

66. MA (BSC): Semisolid DF 92 PASTES Semisolid preparations containing as much as 50% powder dispersed in fatty bases Prepared in the same manner as ointments, by direct mixing or the use of heat to soften the base prior to incorporating the solid Difference from ointments Pastes are usually stiffer and less greasy , applied thickly on dressings rather than spread on the skin Pastes have more absorption capacity than ointments U sed principally as absorbents , antiseptics, protective ( as sun block) , to soothe broken skin surfaces A bsorbing harmful chemicals, and so often used in nappy products

67. MA (BSC): Semisolid DF 93 Are emollient but, because of the solid content, porous , hence, perspiration can escape , and less macerating than ointments Remain in place after application with little tendency to soften A bsorb secretions from the site of application , t herefore, preferred over ointments for acute lesions that have a tendency ooze Because of their consistency, pastes localize the action of an irritating or staining material (e.g., dithranol, salicylic acid, coal tar) When levigating agent is to be used, a portion of the base is often used rather than a liquid like mineral oil that would soften the paste PASTES

68. MA (BSC): Semisolid DF 96 Examples Compound Zinc Paste BP Ingredients Zinc Oxide BP Starch BP White Soft Paraffin BP Quantities 250 g 250 g 500 g Use: Used to treat nappy and urinary rash and eczematous conditions. Also forms an effective as a sun block PA C STES .....

69. MA (BSC): Semisolid DF 97 Examples… R X Zinc and Coal Tar Paste BP Emulsifying Wax BP Coal Tar BP Zinc Oxide BP Starch BP Yellow Soft Paraffin BP Mitte 20 g ** Formulation used to treat psoriasis 50 g 60 g 60 g 380 g 450 g PAST C ES .....

70. MA (BSC): Semisolid DF 98 Calculate for an overage (for 30 g) Method- fusion Melting points of the ingredients: Emulsifying Wax BP White/Yellow Soft Paraffin BP 52 C 38–56 C Weigh 1.8 g Zinc Oxide BP and 11.4 g Starch BP and mix by doubling-up Examples… PAST C ES .....

71. MA (BSC): Semisolid DF 99 Place the Emulsifying Wax BP into an evaporating dish and melt over a water bath Add the c oal t ar and half of the y ellow s oft p araffin to the evaporating basin, stir until melted Add the remaining Yellow Soft Paraffin stir until melted Cool to approximately 30 C and add the powders and stir constantly until cold Weigh 20g of the paste, transfer to an amber glass jar, label and dispense Examples… PAST C ES .....

72. MA (BSC): Semisolid DF 100 Labeling: Zinc and Coal Tar Paste BP For External Use Only Do not use after (3 months) 20 g Patient name --------- Date of dispensing ------------- Examples… PAST C ES .....

73. MA (BSC): Semisolid DF 101 CREAMS ‘Cream’ in pharmacy and medicine is applied to viscous or semi- solid emulsion preparations; C onsist of solutions or dispersions of one or more medicaments in suitable base The term is widely used in the pharmaceutical and cosmetic industry , and pref f er than ointments; They are generally easier to spread In case of cream of the O/W emulsion type, easier to remove than many ointments Creams are applied to the skin for as p rotective , b eautifying , t herapeutic or prophylactic purposes

74. MA (BSC): Semisolid DF 103 Creams… Creams may contain antimicrobial preservatives unless the medicaments or bases have sufficient intrinsic bactericidal and fungicidal activity T ypes:- Oil-in- Water (O/W) and Water- in- Oil (W/O) Oil- in- water creams Known as aqueous ( Vanishing ) creams , most useful as they are water-washable Best bases for rapid absorption and penetration of drugs They are thin , white and smooth in consistency People often prefer O/W creams because: S preads more readily , less greasy Evaporating water soothes the inflamed tissue Used for oozing or weeping surface

75. MA (BSC): Semisolid DF 106 Water- in- Oil creams Also called as oily creams Are used for emollient and cleansing purposes Are creamy , white or translucent and rather stiff Creams…

76. MA (BSC): Semisolid DF 107 Compounding Procedure for Creams Always make an excess (overage) Determine which ingredients dissolve in the oil phase and aqueous phase. Dissolve water- soluble ingredients in the aqueous phase mixed, and heated to 60 C Substances soluble/miscible with the oily phase should then be stirred into the melt Melt the fatty bases (usually including the emulgent) over a water bath at the lowest possible temperature Start with the base having the highest MP. These should be cooled to 60 C

77. MA (BSC): Semisolid DF 109 Compounding… Disperse phase should then be added to continuous phase at same temperature ( thermometer should be used) Resulting emulsion should be stirred until cool  Abnormal creams S eparation of high MP components G ranular product Non uniform apperance

78. MA (BSC): Semisolid DF 110 Example R X Cetrimide Cream BP Cetrimide BP Cetostearyl Alcohol BP Liquid Paraffin BP FBC water Mitte 20g Sig. Apply to the abrasion tid 5 g 50 g 500 g 445 g ** Used as an antiseptic cream

79. MA (BSC): Semisolid DF 111 Example… Weigh required amounts of the ingredients Melt Cetostearyl Alcohol BP in an evaporating basin over a water bath to a temperature not >60°C Add Liquid Paraffin BP to the molten Cetostearyl Alcohol BP and remove from heat Stir to form the oily phase Heat the freshly boiled and cooled purified water to 60°C in a beaker

80. MA (BSC): Semisolid DF 112 Example… Add the Cetrimide BP to the FBC water & remove from heat Stir to form the aqueous phase When both are at about 60°C, add the aqueous phase to the oily phase with constant, not too vigorous stirring Stir until cool enough to pack Weigh 20 g of the product , P ack into a collapsible tub e or amber glass jar, Label and dispense

81. MA (BSC): Semisolid DF 113 Example… Labeling: Cetrimide Cream BP 20 g Apply to the abrasion THREE times a day. For external use only Do not use after (4 weeks) Pt Name: Date of dispensing

82. MA (BSC): Semisolid DF 114 Examples… Lindane cream 1% ( hexachlorocyclohexane cream ) Formulation MF Lindane 1 g Emulsifying wax 14 g Liquid paraffin 8 g Methylparaben 0.15 g Water to 100 g Send 50g Sig. apply to the affected area only once Use: treatment of scabies and lice infestations

83. MA (BSC): Semisolid DF 115 Examples… Preparation: Melt together the emulsifying wax and the liquid paraffin over gentle heat to approximately 60 °C and mix. Dissolve the lindane in this mixture. Boil 75 ml water for 1 minute and dissolve the methylparaben in this water. Allow the solution to cool to approximately 60 °C. Add the paraffin/ wax mixture to the solution under rapid stirring. Stir gently until cold. Add enough FBC to produce 50 g cream. Stir until homogeneous.

84. MA (BSC): Semisolid DF 116 Example… Ex 2) Hydrocortisone Cream BPC Hydrocortisone BP Chlorocresol BP Cetomacrogol Emulsifying Ointment BP FBC water 10 g 1 g 300 g 689 g ** Used to treat eczema

85. MA (BSC): Semisolid DF 117 Dilution of Proprietary Creams It is common to dilute proprietary creams to produce less potent products Care should be taken to prevent microbial contamination Appropriate diluent should be used Diluted creams should be used within two weeks of preparation

86. Dilution… Examples of diluents: 1.Cetomacrogol Cream BP Cetomacrogol Emulsifying 300g 1g 1000g Ointment BP Chlorocresol BP FBC water to 2. Aqueous Cream BP Emulsifying Ointment BP 300g Phenoxyethanol BP 10g FBC water 690g 3 . Buffered Cream BP Sodium Phosphate BP 25g Citric Acid BP 5g Chlorocresol BP 1g Emulsifying Ointment BP 300g FBC water 669g MA (BSC): Semisolid DF 119

87. MA (BSC): Semisolid DF 120 Dilution… Rx Dermovate Cream 1:3 Sig. Apply thinly bid Mitte: 50 g 1part cream plus 3parts diluent  total 4parts (100%) % of cream = 25; % of diluent = 75 Weigh required quantities for 50g (overage ~ 60g!) Triturate the d ermovate c ream with the diluent on a tile Weigh 50g and pack in tube or jar

88. MA (BSC): Semisolid DF 121 Dilution… Labeling Dermovate Cream 25% w/w 50 g To be spread thinly TWICE a day For external use only Do not use after (2 weeks) The product contains: Dermovate Cream Diluent 25% 75% Date of dispensing ----- Name of Patient----

89. MA (BSC): Semisolid DF 123 Packaging of Creams When the risk of contamination in use is considered to be minimal as in o ily creams, wide- mouthed jars may be used The container must be well closed and prevent water evaporation Collapsible metal/flexible plastic tubes are to be preferred since these reduce the risk of contamination in use Most proprietary products are packed in tubes

90. MA (BSC): Semisolid DF

91. MA (BSC): Semisolid DF 124 GELS Transparent or translucent semi- solid preparations, consisting solutions or dispersions of active ingredient(s) in suitable hydrophilic or hydrophobic bases rendered jelly like by addition of gelling agents Formed when solvent is entrapped by three dimensional network of gelling agent Gelling agents used: Macromolecules such as carbomer; cellulose derivatives such as CMC or HPMC; and natural gums, such as tragacanth, alginate, pectin, carrageenan Dispersed solids , e.g., kaolin, bentonite

92. Gels… Gels are sometimes called jellies The vehicle may be aqueous, hydroalcoholic, or non- aqueous Xerogels are gels in which the vehicle has been removed, leaving a polymer network, e.g., polymer films Based on the nature of the three- dimensional network of dispersed particles (gelling agents), two types of gels are available MA (BSC): Semisolid DF 125

93. MA (BSC): Semisolid DF 126 Types of Gels Single- phase gels: Gels in which macromolecules , are uniformly distributed throughout a liquid No apparent boundary between dispersed macromolecules and the liquid Hydrophilic polymers behave as lyophilic colloids and Their unique physical properties result from the self- association of the dissolved polymer and its interaction with the aqueous medium

94. MA (BSC): Semisolid DF 127 Single- phase gels.. Two types of self- associations termed irreversible and reversible can occur between polymer chains Type 1 or Type 2 (physical) gels Type 1 gels (chemical gels): Often termed hydrogels The interaction between the polymer chains is covalent Mediated by molecules that cross- link the adjacent chains Do not exhibit flow when exposed to an applied stress due to the inability of the stress to overcome covalent bond

95. MA (BSC): Semisolid DF 128 Type 1 gels… Due to their elastic properties they store an applied stress to return to their equilibrium position Absorb a large mass of fluid while retaining their mechanical properties Hydrogels are clinically used as wound dressings

96. MA (BSC): Semisolid DF 130 Type 2 gels Interactions between polymer chains are reversible and facilitated by weaker bonds, e.g., hydrogen bonding Application of stresses will end in the temporary destruction of these bond, thereby enabling the formulation to flow Type 2 gels are rheologically referred to as pseudoplastic ( shear- thinning ) systems Removal of stress the intermolecular bonds are reformed and the viscosity of the formulation returns to its equilibrium value

97. MA (BSC): Semisolid DF 132 Type 2 gels… Majority of pharmaceutical gels are type 2 gels Commonly used polymer types:  Cellulose derivatives  Polysaccharides from natural sources  Polyacrylic acid

98. MA (BSC): Semisolid DF 133 Type 2 gels… Factors affecting gelation: Gelation will occur whenever there is sufficient polymer polymer interaction Concentration of polymer MW of polymer Nature of the solvent pH of the solvent Ionic strength of solvent phase Temperature

99. 2. Two- phase gels Gels based on dispersed solid particles Dispersed solids will undergo flocculation that extends throughout the system to establish a continuous solid particle network Often referred to as a magmas Milk of magnesia(magnesia magma), consists of a gelatinous precipitate of Mg(OH) 2 , Al(OH) 3 gel Vehicle entrapped in the voids between particles MA (BSC): Semisolid DF 134

100. MA (BSC): Semisolid DF 135 Components of Gels In addition to gelling agent and water, gels may contain drug substance, C o- solvents such as alcohol and/or propylene glycol; P reservatives such as methylparaben and propylparaben or chlorhexidine gluconate; and S tabilizers such as edetate disodium Additives - Buffers , p reservatives , a ntioxidants h umectants ,f lavors/sweetening agents (for oral gels) , c olors

101. MA (BSC): Semisolid DF 137 Uses Gels have a number of uses: Anaesthetic gels , spermicidal gels. Coal tar gels for treatment of psoriasis or eczema Lubricant gels Medicated gels may be prepared for administration by various routes including the skin, the eye, the nose, the vagina, and the rectum Examples of Topical Gels Clindamycin and Benzoyl peroxide in carbomer for acne vulgaris Clobetasol propionate in carbomer as antipruritic Tretinoin in HPC for acne vulgaris

102. MA (BSC): Semisolid DF 139 Preparation of Pharmaceutical Gels Generally the water soluble components/excipients are initially dissolved in the vehicle in a mixing vessel with mechanical stirring Heat all components of the gel (with the exception of water) to approximately 90 _x0001_ C. Polymer must be added to the stirred mixture slowly to prevent aggregation Mixing rate must not be excessive to prevent entrapment of air

103. MA (BSC): Semisolid DF 142 B est Wishes!

104. MA (BSC): Semisolid DF 140 Reading Assignment Differentiate the following terminologies: Syneresis Imbibition Swelling