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1. Integrated Physical Pharmacy and Pha r mac e utics - I I (IPP-II) 1 6/6/2024 By: Abera J 1

2. Course Content Semisolid Dosage forms Suppositories and Pessaries Micromeritics Powders and granules Diffusion and Dissolution Kinetics and Drug Stability Introduction to radiopharmaceuticals Incompatibilities in formulation Cosmetics Veterinary dosage forms 6/6/2024 By: Abera J 2

3. 1. Semisolid Dosage Forms 6/6/2024 By: Abera J 3

4. Outline Int r o d uctio n to semi s o li d s Classification of semisolid R h eol o g ical p r o p e r ties of s emi s oli d s Factors influencing percutaneous absorption 4 6/6/2024 By: Abera J 4

5. Int r od u ction to semisolids Definition : products of semisolid consistency and applied to skin for therapeutic or protective action or cosmetic function. Tend to alleviate or treat a pathological condition Pr otec t ion again s t a ha r mfu l e n vi r o n ment. They have the property to cling to the skin or mucous membrane for a p r otracted pe r iod of t ime E xert their therapeutic effect through protection and occlusion Inten ded for l o calize d d r ug del i v e r y …….. applied topically to the skin, cornea, rectal tissue, nasal mucosa, v a g ina, b uccal tissu e , ext e r nal ear lini n g , e tc 6/6/2024 By: Abera J 5

6. Introduction … P h ysical Pr o pe r ties : - Smooth t e xtu r e Ele g an t in app earance Non - de h ydr a ting Non - g r it t y Non g r easy an d n o n - stainin g Non - h y g r o s cop ic 6 P h ysi o l o g ical Pr o pe r ties : - Non - i r r it a ting Do not alter membrane / skin functioning Misci b l e with sk in secr etion H a v e l o w sen si tiz a tion in d ex Ide a l P r ope r tie s o f Sem i so l id Dosag e Fo r ms 6/6/2024 By: Abera J 6

7. Introduction … Classification of Semisolid dosage forms Semiso li d d o sage fo r m s inc lu d e ; O i n tments P a s tes C r eams G e ls Ointments ……. S emisolid preparations intended for external application to the sk in or m uco us mem b ra n es The semisolid vehicle into which drug substances may be incorporated in p r epa r ing med i c a ted oi n tments … … Ointment b as e s 7 6/6/2024 By: Abera J 7

8. Ointment bases recognized for use as vehicles fall into four general classes: T he h yd r ocar b o n ba s es T he ab s o r ptio n ba s es T he w a ter - r em o v a b l e ba s es T he w a ter - s o lu b l e ba s e s . Each therapeutic ointment possesses as its base a representative of one of these fo u r general clas s es 8 Classification… 6/6/2024 By: Abera J 8

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10. Clas s ific a tion ... Cream s A re semisolid preparations containing one or more medicinal agents dissolved or dispersed in either a W/O emulsion or an O/W e m ulsio n or in ano ther t y pe of w a ter - w as h a b l e ba s 10 M ore recently the term has been restricted to products consisting of oil- in - w a ter (O/W) e m ul s i o ns or aqueous microcrystalline dispersions of long-chain fatty acids or alcohols that are water washable and more cosmetically acceptable. 6/6/2024 By: Abera J 10

11. Classification … Gels: – are semisolid systems consisting of dispersions of small or large molec u le s in a n aq u eou s li q uid v ehicle r end e r ed jel l yli k e b y t he a d diti o n of a gel l ing age n t A re transparent , non-greasy, semisolid systems generally applied externally for their medication, lubrication and miscellaneous purposes. Pastes : – semisolid dispersion system, where a solid particles (> 20%, e.g. ZnO) are dispersed in ointment bases - mostly oleaginous (Petrolatum) 6/6/2024 By: Abera J 11

12. Rheological properties of semisolids S e mis o li d do sage fo r m s exhi b it diffe r ent rheolo g ical p r op e r ties S e mis o lid s do no t f l o w a t l o w shea r stresse s b ut un dergo r e v e r si b le defo r m a tion li k e elastic s o li d s . When a characteristic shear stress , called the yield value or yield stress, is e xceeded, th e y fl o w li k e liqui d s . At a stress below yield value no flow will be formed but only elastic deformation. When the yield stress is exceeded, the network is partly ruptured and fl o w occu r s . Gels or jellies are characterized by a comparatively high degree of elasticity. 6/6/2024 By: Abera J 12

13. Rheological properties … P aste s - P aste s h a v e lit t l e elasticity Cannot recover their shape except from very small deformations. At stresses above their yield values, pastes turns into free-flowing liquids ( plasticity ). Brownian motion builds up the networks in gels and pastes and restores them when they have been ruptured by stress higher than yield stress. 6/6/2024 By: Abera J 13

14. Rheolo g ic a l p r ope r ties … Semiso li d s with high yield v alue s a re desc r ibed a s “ h ar d ”. When their plastic viscosity is high , they are described as “stiff ”. Instrument for determining the rheological properties of pharmaceutical semi s o li d a r e ; R o t a tion a l visco mete r ……… measure viscosity by analyzing the torque required to rotate a spindle submerged in a fluid at a constant speed.  Con e - pl a te viscomet e r ……… are rotational viscometers that use a narrow-angled cone placed on a horizontal flat plate.  6/6/2024 By: Abera J 14

15. Skin structure S k in als o k n o wn a s cutane o us mem b ra n e or inte g ume n t E xternal membranous covering of an animal body The largest organ of the body, it is thin at some places (eye lids , thickness =0.5 mm ) where as thick at other places (sole of foot, palm of hand , thickness=5mm ). A v erage thi c k n ess of s kin is 1 - 2mm ( .04 -0.0 8 in ) . 6/6/2024 By: Abera J 15

16. Skin structure … Skin consists of three layers : Epidermis, dermis and su bcutaneous 6/6/2024 By: Abera J 16

17. Skin structure … Epidermis The superficial , thinner portion composed of keratinized stratified s q uam o u s epithelial t is s u e I t is nourished by diffusion of nutrients from a vascular network of dermis Co m p o sed of 4 t ype of cells 1. k er a tino c y t es 3. langerha n s cell 17 2. M elano c y te s 4. M er k el cell 6/6/2024 By: Abera J 17

18. Skin structure … 20 Ker a tino c ytes : ( k er a tino = h o r n y li k e , c y t es=cell) 90 % of epide r ma l cells ar e k er a tino c y t e s . Responsible for production of keratin …a tough fibrous protein P rotec t the skin and underlying tissues from heat, microbes and chemical. Me l ano c ytes : ( Mela n o = b la c k, c ytes= cell) 8% of epi d e r ma l cells a re melano c y t e s . Produces a pigment melanin (a yellow red or black brown pigment) C on t r i b ute in skin col o r Abs o rb s dama g ing UV light 6/6/2024 By: Abera J 18

19. Skin structure … 21 La n gerh a ns cells Participate in immune responses against microbes that invade the skin Helps other cells of immune system to recognize an invading microbe an d des t r o y it. Merkel cell Participate in detection of touch sensation. 6/6/2024 By: Abera J 19

20. Skin structure … Dermis The sensitive connective tissue layer of the skin located below the epidermis , C ontaining nerve endings, sweat and sebaceous glands , and blood vessels, hair follicles, fibroblast, histocytes and lymph vessels. Composed of strong connective tissue containing collagen (for strength ) an d elastin (for st r et c h ) 6/6/2024 By: Abera J 20

21. Skin structure …. Hypodermis Below the dermis is hypodermis also known as subcutaneous layer Loose layer of connective tissue which is anchored to the underlined tiss ue ( m u s cle an d b o nes ). Most fat cells are present in hypodermis (adipose tissues) A cts as insulator to protect the body from excessive heat and cold environment 6/6/2024 By: Abera J 21

22. Skin structure … Skin a pp e nd a ges …… Sweat glands and hair follicles 1. S w e a t glan d s ……… are coiled tubules in the dermis which open on to the skin surface; they can be sub-divided in to two classes ; Eccrine glands Are found all over the body  and  secrete a watery product that cools the skin .  I n v ol v ed in th e r egul a tion of b o d y temper a tu r e b y w a ter e lim i n a tion . About two million eccrine sweat glands on the average human body. 6/6/2024 By: Abera J 22

23. Skin structure … Apocrine sweat glands Are larger than eccrine sweat but few in number. Mainly found in the armpits and perianal area , and secrete a more viscous, odorous product A p oc r i n e s w e a t d i ffe r s in co m p o si tion f r om ecc r i n e a n d m a y be cl o u d y an d co l or ed 6/6/2024 By: Abera J 23

24. Skin structure … 2.Hair follicles Hair foll i cles a re se b u m - filled o peni n gs f r om wh i c h k er a tino us hai r filaments p r ot r ud e . Follicles occupy about 0.1% of the skin surface area; but are absent from plantar and palmar surfaces, the red areas of the lips, and parts of the genitalia. Hair follicles    anchors each hair into the skin and responsible for hair color, hair growth and hair texture. 6/6/2024 By: Abera J 24

25. Functions of skin Co n tainmen t of bo d y flu i d an d tiss ue Pr otec t ion f r om e xte r nal s ti m uli Mic ro b ial ba r r ier Chemica l ba r r ier R a d i a tion ba r r ier T h e r ma l ba r r ier 6/6/2024 By: Abera J 25

26. P ercut a neous a bs o r ption : the abs o r ption of su b s tances f r om outside the skin to positions beneath the skin , including entrance into the b lo o d st r eam. Drugs may penetrate intact skin after topical application through ; T he w all s of t he ha i r foll i cles, T he s w e a t g lan d s T he sebaceous gl a nd s, T h r o u gh the cells of t he h o r n y l a y er Percutaneous absorption (Transdermal drug delivery) 6/6/2024 By: Abera J 26

27. Percutaneous absorption … T h e mai n r o u te for the penetr a tion of d r ug is general l y t h r o u gh the epi d e r ma l l a y e r s ( b /c of s urface a r ea ). The stratum corneum is the outermost ‘horny’ layer of skin, comprising about partially desiccated, dead, keratinized epidermal cells. It is the r a t e- lim i ting ba r r ier to perc u taneou s d r ug trans p o r t 6/6/2024 By: Abera J 27

28. Percutaneous absorption … Transport of lipophilic drug molecules is facilitated b y their d is s o luti on into intercellular li p ids Absorption of hydrophilic molecules into skin can occur through ‘ pores ’ or open ings of t he ha i r foll i cles an d seb aceo u s glands But, the relative surface area of these openings is barely 1% of the total s k in s u r f ac e . L im i ts the amo u nt of d r ug ab s o r ptio n 6/6/2024 By: Abera J 28

29. 3 Factors Affecting Percutaneous Absorption: Nature of Skin 3 6/6/2024 By: Abera J 29

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31. Factors Affecting Percutaneous Absorption: Nature of Vehicle 6/6/2024 By: Abera J 31

32. Factors influencing … Miscellaneous Factors Si t e of applic a tion Ti m e of c o ntact Am o u n t of p r epar a tion em p l o y ed pH o f ap p lie d pr e p ar a tion pH o f Skin Molecular st r uctu r e et c . 6/6/2024 By: Abera J 32

33. Maximizing the bioavailability of drug to skin D r ug or p r od r ug selec t ion Hydration Ultrasounds ( S onophoresis ) Iontophoresis S t r a tum c o r neu m r em o v al Chemica l penetr a tion enh ance r s 6/6/2024 By: Abera J 33

34. Materials used to enhance absorption ; S urfactants, dimethylsulfoxide (DMSO), dimethylacetamide, dimethylformamide, alcohol, acetone, propylene glycol, and polyethylene glycol. Chemical penetration enhancers 6/6/2024 By: Abera J 34

35. Mechanism of action for percutaneous absorption enhancers Reduction of the resistance of the stratum corneum Alteration of the hydration of the stratum corneum Effecting a change in the structure of the lipids and lipoproteins in the cellular channels, through denaturation Ca r r ier me c ha nis m in t he tran s p o r t of i o n iza b l e d r ugs 6/6/2024 By: Abera J 35

36. Iontophoresis and Sonophoresis Ionto p ho r esis: the deli v e r y of c harged c hemical comp oun ds ac r os s the skin mem b ra n e u s ing a n applie d elec t r ical fiel d . Eg: lidocaine, amino acids/peptides/insulin, verapamil, and propanolol Sonophoresis : high-frequency ultrasound , is also being studied as a means to enh anc e trans de r ma l d r ug deli v e r y Eg.: hydrocortisone, lidocaine, and salicylic acid in such formulations as ge l s, c r eams an d loti o ns 6/6/2024 By: Abera J 36

37. Advantage of Topical Drug Delivery Avoids gastrointestinal drug absorption difficulties Substitutes for oral administration of medication when that routes is unsuitable. A v oi d s fi r s t - pa s s effect Provides the capacity for multiday therapy with a single application 6/6/2024 By: Abera J 37

38. Advantage of Topical Drug Delivery… Pr o vides s u stain ed an d con t r olled ad m in i str a tion (f o r c h r o n ic di s eases ) . Pr o vides capac i ty to te r mi n a te d r ug effect ra p id l y . P e r mi t self ad m in i str a tion Extends the activity of drugs having short half-life through the reservoir of drug present in the therapeutic delivery system 42 6/6/2024 By: Abera J 38

39. Disadvantage of Topical Drug Delivery U nsuitable for drugs that irritate or sensitize the skin. On l y r el a ti v e p o tent d r ugs a re su ita b l e can d id a tes Technical difficulties are associated with the adhesion of the systems to different skin types and under various environment conditions P o o r diff u s ion of l arge molecules 39 6/6/2024 By: Abera J 39

40. OINTMENT S & P ASTES 40 6/6/2024 By: Abera J 40

41. Pharmaceutical ointments are semisolid systems that are applied externally p r ima r i l y to the sk in mucous membranes e.g. the rectum, the vagina, the eye. Medicated ointments: for the t reatment of infection, inflammation Non-medicated ointments are commonly used as emollient/ lubricating properties 41 6/6/2024 By: Abera J 41

42. Advantages of pharmaceutical ointments, pastes, and gels Ointments easily spread on skin , being retained at the site of app lic a tion a s a n occl u si v e l a y er the r e b y p r e v enting m o is tu r e lo s s f r om t he s ki n . useful in restoration of the physical characteristics of the skin (e.g. d u e to in flamm a tion ) 42 Ointments are associated with lubricating properties that may be employed to reduce trauma of an affected site upon spreading. 6/6/2024 By: Abera J 42

43. Pha r maceutica l pa s tes a re general l y co m p o sed of ointment ba s es th a t contain a high concentration of dispersed drug. The viscosity of pharmaceutical pastes is greater than that of ph a r maceutica l oi n tme nts 43 The increased viscosity of pharmaceutical pastes ensures that a thick film of the dosage form is applied to the site of action s h o ws excellent pe r si stence Advantages of pharmaceutical ointments, pastes, and gels… 6/6/2024 By: Abera J 43

44. Advantages of pharmaceutical ointments, pastes, and gels… Due t o the h igh s o li d s con tent , P aste ; act to absorb moisture and chemicals within the exudates. e n a b le s to b e u s ed a s a s u n b lo c k. The chemical stability of therapeutic agents that are prone to hydrolysis will be dramatically enhanced by formulation within pharmaceutical oi n tme nts and past e s . Pharmaceutical gels may be formulated to provide excellent spreading properties and will provide a cooling effect due to solvent evaporation. 44 6/6/2024 By: Abera J 44

45. Disadvantage 49 Ointments are generally greasy and difficult to remove ( cosmetically unacceptable ). Pharmaceutical pastes are generally applied as a thick layer at the required si te ( cos metical l y u n accepta b le ). S t ai n ing of clothes is the p r o b lem Problematic in ensuring spreading of the DF over the affected site. The viscosity of pharmaceutical ointments, and in particularly pastes 6/6/2024 By: Abera J

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47. Disadvantage … Problems concerning drug release from pharmaceutical ointments may occur if the drug has limited solubility in the ointment base Pharmaceutical pastes are generally not applied to the hair du e to difficulties as s oci a t e d wi t h r em o v al. Drugs that are prone to hydrolysis should not be formulated into aqueous gels. 6/6/2024 By: Abera J 47

48. Ointm e nts Clas s ific a tion of Ointments ; Based on their penetration , Acc o r d i n g to thei r ther ap e utic u s e s . 6/6/2024 By: Abera J 48

49. Ointments … According to their penetration properties Ep i de r mi c oi n tments Ac t on epide r mi s & p r od uce loca l eff e ct. Used as protectives, antiseptic, local anti-infectives & parasiticides. En d o d e r mi c oi n tments Act on deeper layers of cutaneous tissues. P a r tial l y abs o rbe d & ac t a s a emoll i ents, sti m ula n ts & loca l i rr itant s . Diade r mi c oi n tme nts Meant for deep penetration R elease the medicaments and p r o d uce systemic effec t s . 6/6/2024 By: Abera J 49

50. Ointments … Acco r ding t o thei r th e r a pe u ti c uses ; A n tibi o tic oi n tments ……. u sed to kill micro-organisms. E g - bac i tracin, Neo m ycin, Chl o r te t ra c ylclines, et c . Antifungal ointments- Inhibit or kill the f ungi. E g - Benz o ic aci d , sali c ylic acid , n yst a tin et c . 6/6/2024 By: Abera J 50

51. Ointments… 3. Anti-inflammatory ointments…… Relieve inflammatory, allergic & pruritic conditions. Eg- Betamethasone valerate, Hydrocortisone & its acetates. 4. Anti-pruritic ointments……… Relieve itching Eg- Benzocaine & coal tar 5. Astringent ointments….. Causes contraction of skin & decreases discharge. Ex- Calamine, ZnO, Acetic acid, Tannic acid 6/6/2024 By: Abera J 51

52. Ointments … 6. K er a to l y t ic O i n tmen ts … Used to r em o v e or soften the ho r n y l a y er of the s ki n . E.g - Resorcinol, salicylic acid & sulphur Counter-irritant Ointments …… A p plied local l y to i r r it a te ski n , thus r edu ci n g or relieving another irritation or deep seated pain. E. g - met h yl salic yl a t e , io di n e , oleo r esin 8. Protectant Ointments …… Protect skin from moisture, air, sun rays, chemicals. E. g - Calamin e , Z n O , si lic o nes , ti t an i um di o xi d e et c . 6/6/2024 By: Abera J 52

53. Ointments … 9. A n tidan d r uff oi ntme n ts ….. used to treat or prevent dandruff E g - Sali c ylic acid , ce t r imi d e . 10. Ointment F or Pso r iasis t r e a tme nt E.g.- coal tar, coticosteroid, & salicylic acid mixed with s u ita b l e oi n tment ba se . 11. P ara s iticide oi n tments ……………... Destroy or inhibit living infestation like ticks & lice. E. g . - Benzyl benz o a t e , hex a c hl o r id e , s u lp h ur et c . 6/6/2024 By: Abera J 53

54. Ointments … The formulation of ointments and pastes involves the dispersal or dissolution of the selected therapeutic agent into an ointment base The physicochemical properties of the ointment base are fundamental to ; T he clinical N on-clinical performance of this type of dosage form. 6/6/2024 By: Abera J 54

55. Ointments … 58 The choice of ointment base is dependent on several factors , including ; Dermatological factors A b s o r pti o n an d pene tr a tion Mis ci b ility with s k i n secr etion Compatibility with skin secretion No n - i r r itant ( e y e oi n tments) Patient skin condition ( old, baby and young) T he site of a p plic a tion 6/6/2024 By: Abera J 55

56. 2. Pharmaceutical factors The r eq u i r ed r a te o f d r ug r elease; The chemical stability of the drug; and The effect of the therapeutic agent on formulation viscosity 6/6/2024 By: Abera J 56 Ointments …

57. Types of base for ointments and pastes 59 There are four types of base that are used to formulate pharmaceutical oi n tments an d pa s tes H ydrocarbon; A bsorption; W ater-miscible/removable ; and W ater-soluble . 6/6/2024 By: Abera J 57

58. Types of base … Hydrocarbon bases ( Oleaginous bases ) N on-aqueous formulations R est r ict w a ter lo s s f r om t he s ite of app lic a tion Due to the formation of an occlusive film Excellent r et e ntio n o n t he s kin Pr edo mi n ant l y h yd r o p h o bic Diffic u l t t o r em o v e f r om the s k in b y w as h i n g D i ffic u l t to a p p l y to ( s pr ead o v er) w et s u r f ace s ( e . g . m uc o us mem b ra n es, w et ski n ) 6/6/2024 By: Abera J 58

59. Hydrocarbon bases … Small amount of water ( 5%) can be incorporated into it with difficulty Can be protective to water labile drugs such as tetracycline and bacitracin . G r easy an d can stain clothi n g . Chemical l y ine r t 59 6/6/2024 By: Abera J 59

60. Hydrocarbon bases … E. g . of h yd r ocarb o n base s : P et r ol a tum , U S P Y ell o w pet r ol a tum/pe t r ol a tum jel l y / V aseline Mel t s a t 3 8 - 60 o C White pet r ol a tum , U S P Decolo r ed pet r ol a tum, White petroleum jelly/white vaseline 60 6/6/2024 By: Abera J 60

61. Hydrocarbon bases … Y ell o w oi n tment , U S P Yellow beeswax (5% w/w) + petrolatum (95% w/w ) White oin tment , U S P Whi te bee s w a x + white pet r ol a tum Hydrocarbon bases frequently contain the following components ; hard paraffin ; white/ y ell o w soft par affi n ; and li q uid par affi n (m iner a l oil) 61 6/6/2024 By: Abera J 61

62. Hydrocarbon bases … Hard paraffin A mixture of solid saturated hydrocarbons that are derived from petroleum or shale oil. A colourless or white wax-like material that is physically composed of a mixture of microcrystal. 62 The melting temperature of hard paraffin is between 47 and 65 o c and, U sed to enhance the rheological properties of ointment bases. 6/6/2024 By: Abera J 62

63. Hydrocarbon bases … White/yellow soft paraffin A purified mixture of semisolid hydrocarbons that are derived from petroleum. Con s ists of mic r oc r ys t al s embedded in a g e l comp o sed of liq u id a nd am o r p h o u s h yd r ocar b o n s . The melting range of the soft paraffins is between 38 and 60 o c . Used as an ointment base without the need for additional components, although it may be combined with liquid paraffin 63 6/6/2024 By: Abera J 63

64. Hydrocarbon bases … Liquid par a ff in ( mineral o i l , Liquid petro l a tum) M ixture of refined liquid saturated hydrocarbons obtained from petroleum U sually formulated with white/yellow soft paraffin to achieve the r equ i r ed viscosi ty for app lic a tion to the r equ i r ed si t e . Formulations containing liquid paraffin require the incorporation of an antioxidant due to the ability of this material to undergo oxidation 64 6/6/2024 By: Abera J 64

65. Absorption bases Absorption bases , unlike the hydrocarbon types, are hydrophilic and, therefore, can absorb considerable amounts of water or aqueous solutions. I. Non-emulsified bases These bases absorb water and aqueous solutions to produce water-in- oil ( W/O ) emulsions. Compared with the hydrocarbon bases:- They are less occlusive, They assist oil-insoluble medicaments to penetrate the skin They are easier to spread. 6/6/2024 By: Abera J 65

66. Absorption bases … Typically non-emulsified bases are commonly composed of: o n e/mo r e par affi n s , an d a ste r o l - ba s ed e m ul s ifying ag e nt. Exa m ples : ( 1 ) lan o li n ( w o o l f a t); w oo l alcoh o ls ; and bee s w a x (white or y ell o w). 66 6/6/2024 By: Abera J 66

67. Absorption bases … Lanolin (wool fat) Lan o li n is a w a x - li k e m a te r ial th a t is de r i v ed f r om sheep ’ s w o o l. It is a v aila b l e in t w o fo r ms , t e r med as; A n h yd r o u s lan o li n ( w o o l f a t) an d h yd r o u s lan o li n . Anhydrous lanolin C alled w o o l w ax , w o o l f a t , or w o o l g rease , a g r easy y ell o w s u b s tance C ontains < 0.25% o f w a ter 67 6/6/2024 By: Abera J 67

68. Absorption bases … Typically mixed with paraffins to produce an ointment base Can absorb approximately twice its own weight of water to p r od uce w a t e r in oil e m uls i on s . The usual concentrations of lanolin used in ointments (e.g. Simple Oi n tment BP) r ang e f r om 5 to 1 % w/ w . 68 6/6/2024 By: Abera J 68

69. Absorption bases… W o o l f a t is a maj o r con stituent of Simple Ointmen t an d E y e Ointment Simple ointment B.P Hard par affi n ………5 g Ce t o s te r yl alcoh o l….50g W o o l f a t ……………. . 5 g Soft paraffi n ……….85 g E y e Ointme n t B .P Liq uid par affi n …. . 1 0g W o o l f a t…………10 g Yellow soft paraffin.......850g 6/6/2024 By: Abera J 69

70. Absorption bases … 74 Wool alcohols A c r u d e mi x tu r e of st e r ols an d t r ite r pen e alco h ols Added to mixtures of paraffins (hard, white/yellow soft or liquid) to p r od uce the r equi r ed con s isten c y . The inclusion of wool alcohols (5% w/w) results in a 300% increase in the con centr a tion of w a ter e . g . w oo l alcoh o l oi n tme nt B .P 6/6/2024 By: Abera J 70

71. Absorption bases … Beeswax (white or yellow) A wax that consists of esters of aliphatic alcohols (C 24 –C 36 ) and linear aliphatic fatty acids (up to C36) that is combined with paraffins to produce no n - e m ul s ified ba s e s . White beeswax is the bleached form of yellow beeswax. I ncluded in some ointment bases to increase water-absorbing power. 6/6/2024 By: Abera J 71

72. Absorption bases … W a te r in o il e m uls i ons These are similar in properties to the previous group and are capable of a b s o rb i ng w a te r . Absorption bases are less occlusive than the hydrocarbon bases and easier t o s p r ead . E g . h yd r o u s lan o li n , whi c h is a mi x tu r e of la n olin an d 2 5 – 3 % w a te r . 6/6/2024 By: Abera J 72

73. Absorption bases … It is used alone as an emollient and is an ingredient of several B.P. oi n tment ba s es, i,e H y d r ou s w oo l f a t ointment Calamin e an d coal tar oi n tment M e t h yl s ali c yl a te oi n tme nt 6/6/2024 By: Abera J 73

74. Absorption bases … Properties of absorption bases No n - e m ul s ified ab s o r ptio n ba s es (a n h yd r o u s) Emollient Occlusive A b s o rb s w a ter Greasy W/O emulsion Emollient Occlusive Contain s w a t e r , abs o rb s add i tional w a t e r Greasy 6/6/2024 By: Abera J 74

75. Water-washable/removable bases W a t e r - misc i b l e bases th a t ar e used to fo r m O/W e m uls i on s . Th e y can be appl i ed to scal p and o t her hai r y re g i o n s . The r e a re 3 official an h yd r ou s w a t e r - misc i b le bases. E m uls i fying oi n tme nt B .P – ani onic Ce t r imi de e m ul s ifying oi n tment B .P – c a tion ic Ce t omac r ogol e m ul s ifying B .P - no n - io n ic 6/6/2024 By: Abera J 75

76. Water-washable/removable bases … Advantages of water-miscible bases A b l e to acco m mo d a te larg e v ol u me s of w a ter A b l e to acc o m m o d a te e x cess m o is tu r e e.g. exudate from abrasions & wounds. Reduced interference with skin function E asi l y w as h ed f r om t he s kin an d f r om clothi n g . R eadily applied to (and removed from) hair, skin. Hence h igh co s meti c acceptability N . B . Oi n tments with h ydrocarbon or a bs o r ption ba s es a re no t very suitable for scalp conditions because their removal is u n pleas an t an d diff icu lt . 6/6/2024 By: Abera J 76

77. Water removable bases … Characteristics of water removable bases Res e m b l e c r eams in t h eir ap p earance May be diluted with water or with aqueous solution W a ter w as h a b le C o ntai n s w a ter Ca n ab s o r b w a ter Non-occlusive Non-greasy 6/6/2024 By: Abera J 77

78. W ater-soluble base s Completely water-soluble bases have been developed from the Macrogols (Polyethylene glycols) Advantages of water- soluble bases W a ter sol u bil i ty Ea s i l y r em o v a l f r om the s k i n Readily miscible with tissue exudates Go o d abs o r ptio n b y t he s kin V aluable when drugs are required to penetrate the skin Go o d sol v ent p r o p e r ties For some water soluble dermatological e.g. Hydrocortisone 6/6/2024 By: Abera J 78

79. W ater-soluble bases … Advantages of water- soluble bases… F r ee f r om g r easiness S a tis f ac t o r y a g e ing p r op e r ties They don’t hydrolyze , rancidity or support microbial growth Compatibility with many dermatological medicaments e . g . - Am m o n i a ted merc u r y , Y ell o w mercu r ic o xi d e 6/6/2024 By: Abera J 79

80. W ater-soluble bases … Disadvantages of water-soluble bases Less bland than paraffins, possibly due to their hygroscopic nature. Reduction in activity of certain antimicrobial agents, due to hydrolysis 6/6/2024 By: Abera J 80

81. W ater-soluble bases … Disadvantages of water-soluble bases … Inability to incorporate large volumes of aqueous solutions b/c Oi n tments will s o ft e n or dissolve the ointment base if the concentration of water is large enough. Its use is usually reserved for the incorporation of soli d therapeutic agents . It may incorporate up to 25% of an aqueous solution if a portion of the lower-molecular-weight polyethylene glycol is replaced with stearyl alcohol. This enhance the mechanical properties of the ointment. 6/6/2024 By: Abera J 81

82. Properties of water-soluble bases W a t e r s o lu b l e and w asha b le Non-greasy Non/less occlusive Lip id f r ee Rel a ti v e l y ine r t Does n ot s u p p o r t mol d g r o w t h Lit tl e h yd r o l ysis , sta b le 6/6/2024 By: Abera J 82

83. Miscellaneous excipient s Miscellaneous excipients of ointments and pastes; Must not adversely affect the physical stability and/or the appearance Other excipients may be included in ointments and pastes, including: A d d itio nal / A lte r n a ti v e s o l v e n ts; P r ese r v a ti v es ; and A ntioxidants . 6/6/2024 By: Abera J 83

84. Miscellaneous excipients … Additional/ A lternative solvents Are hydrophobic liquid components that may be added to ointment bases (p r edomi n ant l y h yd r op ho bic or abs o r ption base s ). Examples inclu de: L i q u i d silic o ne ; V ege t a b l e oi ls ; and O r gani c este r s 6/6/2024 By: Abera J 84

85. Miscellaneous excipients … Antioxidants The antioxidants that are used in ointment bases are similar to those li s ted for e m ul s ion Butyl a ted h yd r o x y an i s o l e ( BHA) But y l a ted h yd r o xytol u nene (BHT ) , E t h yl , p r o pyl or d o d e c yl gall a te s . Chelating agents such as ethylendiaminetetra-acetic acid (EDTA) may als o be u s ed. 6/6/2024 By: Abera J 85

86. Miscellaneous excipients … Preservatives Preservative may not be required in anhydrous ointments because the substrate is generally unfavorable to the multiplication of any contaminating micro-organisms. Ointment with an aqueous component requires effective antimicrobial agents to prevent the growth of organisms that may cause spoilage and pathogenecity . 6/6/2024 By: Abera J 86

87. Miscellaneous excipients … Preservatives… Those used most commonly are ; M ixtures of hydroxybenzoate esters, S orbic acid, P henethyl alcohol, O rganic mercurials and quaternary amm o ni u m co m p o u n d s . 6/6/2024 By: Abera J 87

88. Method of preparation A w el l - mad e oi n tme nt is : - Unifo r m th r o u gho u t , i. e . it con tains no lu m ps of separ a ted high mel t ing point in g r edient of the bas e . Free from grittiness , insoluble powders are finely subdivided and large clumps of pa r ticles a re ab s ent. Methods of preparation must try to satisfy these criteria. 88 6/6/2024 By: Abera J 88

89. Method of preparation … Both in large and a small scale, ointments are prepared by two general methods. Incorporation method Fusion method The method for particular preparation depends primarily up on the nature of in g r edient s . 89 6/6/2024 By: Abera J 89

90. Method of preparation …. I . Inco r por a ti o n method In the incorporation method the component of the ointment are mixed together by various means until a uniform preparation has been attained. Before incorporation the ingredient should have the finest state. On a small scale , as in the extemporaneous cpding of Rx ; Mortar and pestle Ointment tile (Slab) and spatula : may be used to rub the ingredients together. 90 6/6/2024 By: Abera J 90

91. Method of preparation ….. Incorporation method… Mortar and Pestle Used: W hen lar g e q u antiti e s of li q ui d s a re to be i n co r p o r a ted. W hen larg e q u antit y of oi n tment is to be p r epa r ed 91 6/6/2024 By: Abera J 91 Otherwis e , tile and sp a tula is s a tis f acto r y d u e to its large s u r f ac e a r ea.

92. Method of preparation … Incorporation method… 1. Incorporation of solids When preparing an ointment by spatulation , the pharmacist generally w or k s the oi n tment w ith a stain less steel sp a tula with a lo n g , br oad b lad e an d pe r io d ical l y r em o v es the accu m ul a tion of o intmen t on the larger spatula with a smaller spatula. If the component of an ointment are reactive with the metal of the s p a tula ( e . g ., p h eno l) , hard r u b ber s p a tula m a y be u s ed. 92 6/6/2024 By: Abera J 92

93. Method of preparation …. Incorporation of solids… The ointment is prepared by thoroughly rubbing and working the component together on the hard surface with the spatula until the p r od uct is smooth and unifo r m . Gener a lly the ointment base is placed on one side of the working surface, and the powdered components , previously reduced to fine powders and tho r ou gh l y b lende d in the mo r ta r , a r ea placed on the o t he r . 93 6/6/2024 By: Abera J 93

94. Method of preparation … Incorporation of solids… Then a portion of powder is mixed with a portion of the base until uniform , and the process is repeated until all portions of the powder and ba s e a re com b ine d . T h e p o r tion s of p r epa r ed oi n tment ar e then c o mb i ned an d tho r o u gh l y blended by continuous & movement of the spatula and through the co m bi n ed p o r tion s of o intmen t. 94 6/6/2024 By: Abera J 94

95. Method of preparation … Incorporation of solids… When only a small portion of powder is to be added, it may be added in ; I ts enti r e l y to a sm al l p o r tion of o intmen t ba se . If the q u antit y of AI is v e r y small y ou h a v e to u s e l e vi ga ting ag e nt (m iner a l oil, an d g l yce r in ) . After levigation , the dispersion is incorporated with the remainder of the ba s e b y s p a tul a tion or b y usi ng the mo r tar an d pes tle 95 6/6/2024 By: Abera J 95

96. Method of preparation… 2. Incorporation of liquids Any liquids ingredients should be incorporated at the end of levigation. Generally, mortar and pestle is preferred when large volumes of liquid a re ad d ed than a n ointment sla b . Liquid substances or solutions of drugs are added to an ointment only after due consideration of an ointment base’s capacity to accept the v ol u m e r equ i r ed. 6/6/2024 By: Abera J 96

97. When it is necessary to add an aqueous preparation to a hydrophobic base , T he solution first may be incorporated into a minimum amount of a h yd r o p hil i c ba s e an d then th a t mixtu r e add ed to the h yd r o p h o bic ba se . H o w e v e r , al l ba s es, e v en if h yd r o p hil i c , h a v e t heir lim i ts to r et a in l i q u id s , beyond which they become too soft or semi liquid 97 6/6/2024 By: Abera J 97 Method of preparation…

98. Fusion method of preparation All or some of the components of an ointment are combined by being melted together and cooled with constant stirring until congealed. When ointment base contains several ingredients of different melting point ; first add constituent of high melting point and then adding in des cen d ing or d er of meltin g po int. 98 6/6/2024 By: Abera J 98

99. Fusion method… Advantages of melting in descending order of melting point : Quicker Re q u i r e less he a t A v o i d o v er h e a ting of eas i l y melted c onstituent. 99 6/6/2024 By: Abera J 99

100. Fusion method… Those components not melted are generally added to the congealing mi x tu r e a s its is bei n g coo le d an d sti r r ed. Naturally, heat-labile substances and any volatile components are added last when the temperature of the mixture is low enough not to cause decomposition and volatilization of the component. 100 6/6/2024 By: Abera J 100

101. Fusion method… Many substances are added to the congealing mixture in solution , others a re ad d ed a s in s ol u b l e p o wde r s general l y l e vi ga ted with a po r tion of the base. On a small scale ; the fusion process may be conducted in a porcelain dish or g las s bea k e r . On a large scale ; it is generally carried out in large 1 s 1 t 1 ea m - ja c k et ed kittl e s . 6/6/2024 By: Abera J 101

102. Fusion method… On ce con gea led , the oi n tment m a y be p as s ed th r o u gh: A n ointment mill ( in large-scale manufacture ) R ubbed with a spatula or in a mortar ( in small scale ) to ensure a un ifo r m t e xtu r e . Man y medic a ted oi n tments an d oi n tment bases con taini n g s u ch components as beeswax , hard paraffin , stearyl alcohol , and high molec u la r w eight PEG , whi c h do n o t tend thems el v es w ell to mi x tu r e b y inco r p o r a tion , a re p r epa r ed b y fu sio n . 102 6/6/2024 By: Abera J 102

103. Fusion method… After melting; the melted ointment base should be stirred taking care, not to cause localized cooling of high melting ointment constituents . Locali ze d coo li n g can be occu r r ed d u e to : - C o l d sp a tula or sti r r er P u t t i n g the d ish on co l d su r f ace Transferring melted base to cold dish 103 6/6/2024 By: Abera J 103

104. Fusion method… If t he p r od uct is g ran u la r aft e r coo lin g , it has to be r emel t ed wi t h minimum amount of heat and stirred gently until it sets fully. W e us e fu s ion metho d when : - C o n s ti t ue nts a re with h ar d co n si sten c y ( h igh melti n g p o i n t co m p o ne nts ). The medicaments is soluble in melted base. 104 6/6/2024 By: Abera J 104

105. Dang e r o f c hemi cal r eac t ion bet w een steel s p a tula an d s om e r eac t i v e ingredients. Ex. sali c ylic acid , Benz o ic aci d Solutio n : - to mi n imi z e this p r o b lem , u s e b o ne s p a tula, w o oden s p a tula or hard r u b ber s p a tula. Incorporation of aqueous solution in to hydrocarbon base. Solutio n : add ition of w o o l f a t. Incorporation of antibiotics sensitive to hydrolysis Solutio n : - u s e h yd r ocar b o n ba se . 105 6/6/2024 By: Abera J 105 Difficulties encountered in preparation of ointment

106. Packaging and storage of ointment Oi n tments a re us ual l y pa c kaged eithe r : - Jars Tubes J a r s : - M a y be ma d e of glass, u n col o r ed, dar k g r een, ambe r , or b lue or M ad e of pla s ti c , or p orc elain. 106 6/6/2024 By: Abera J 106

107. Packaging and storage of ointment… T u b es: - a re mad e of tin or pla s tic (c o llap s i b l e tube) 107 6/6/2024 By: Abera J 107

108. Packaging and storage of ointment… Ointment jars may be filled on a small scale by packaging the weighed amount of ointment in to the jar by means of a flexible spatula and forcing the ointment down and along the sides of the jar to avoid the entrap m ent of ai r . Ointments prepared by fusion may be poured directly in to the ointment jars for congealing with in the jar. 108 6/6/2024 By: Abera J 108

109. Packaging and storage of ointment… In the large-scale manufacture of ointments, pressure fillers force a s p ecified am o u n t of a n oi n t ment in t o a ja r . Tubes are generally filled by pressure fillers from the open back ( opposite and from the cap end ) of the tube which is then closed and sealed . 109 6/6/2024 By: Abera J 109

110. Packaging and storage of ointment… Tube-filled ointment predominate over jar-filled ointments primarily because th e y a re mo r e co n v enie n t for the p a tien t . 110 Oi n tments i n tubes a re less expos e d t o ai r a nd to potential contamina n ts an d a re the r efore li k e l y t o b e mo r e sta b le ; R emain eff e c tive for lo n ger pe r io d of time Most ointments must be stored at temperature below 30 c to prevent the s o ft e ni n g an d li q uefyin g . 6/6/2024 By: Abera J 110

111. Pastes 1 2 1 Pastes , like ointments, are intended for external application to the skin. They differ from ointments primarily in that they containing large p r o p o r tion of solid m a te r ials as a consequence are thicker and stiffer than ointment. P aste s a re us ed p r inc ipa l l y as ; A bsorbents, A ntiseptics Pr otecti v e , or to s o ot h e b r o k en s k in s u r f aces 6/6/2024 By: Abera J 111

112. Pastes… They are emollient but, because of the powder content, porous , hence, pe r s p ir a tion can e sca p e . The powder absorb exudates , less macerating than ointments with similar base. Are less greasy than ointments because of the absorption of the fluid hydrocarbon fraction to the insoluble particles. 112 6/6/2024 By: Abera J 112

113. Pastes… Most are unsuitable for treating scalp conditions B ecause they are dif f icult t o r em o v e f r om the hai r . Because of the stiffness and absorptive qualities of pastes, they remain in place aft e r app lic a tion with lit t l e tenden c y t o s o ft e r an d fl o w T herefore effectively employed to absorb secretion from the site of application . 113 6/6/2024 By: Abera J 113

114. Pastes… Pastes are therefore preferred for acute lesions that have a tendency toward crusting, or oozing. The film formed on application is opaque and thus can often serve as a sun-block. P ast e s a re p r epared simila r l y t o ointment s . – However, when a levigating agents is to be used to render the powdered component smooth, a portion of the base is often used rather than a liquid like mineral oil 114 6/6/2024 By: Abera J 114

115. Pastes… Among the few pastes in use today is zinc oxide paste (Lassar’s Plain Zinc Paste), prepared by levigating and then mixing 25% each of ZnO and starch and calamine with white petrolatum . The product is very firm and is better able to protect the skin and absorb secr etions than is zi n c o xi d e oi n tment 115 6/6/2024 By: Abera J 115

116. Zinc oxide paste, USP 116 Zi n c o xi d e ….. 25.0% Starch …… 2 5 .0 % Calamine …. 5.0% White pet r ol a tum ……. q. s . 10 0% Procedure : Triturate the calamine with the zinc oxide and starch and incorporate uniformly in the petrolatum by levigation in a mortar or on a glass slab with a s p a tula. A portion of petrolatum can be melted and used as a levigating agent if so des i r e d . 6/6/2024 By: Abera J 116

117. Creams The term ‘ cream ’ in pharmacy and medicine is applied to ; V iscous emulsion or semi-solid emulsion preparation consisting of solutions or dispersions of one or more AI in suitable base and intended for app lic a tion t o the s k in or m uco us mem b ra n e . The term cream is widely used in pharmaceutical and cosmetic industry. 117 6/6/2024 By: Abera J 117

118. C r e a ms… Many patients and physicians prefer creams to ointments. they are generally easier to spread, and, in the case of cream of the O/W e m ul s io n ; Eas i er to r em o v e t han ma n y oi n tments T h e y a re ap p lie d t o the s k in fo r : - Protective Beautifying T h erape u tic or p r o p h ylac t ic p u r p o ses 118 6/6/2024 By: Abera J 118

119. Cre a ms… Creams may contain suitable antimicrobial or preservatives unless the medicaments or bases have sufficient intrinsic bactericidal and fungicidal activity C r eams ar e mai n l y t w o types: - 1 ) . W a te r - in – oil (W/O )…… oi l y c r eam 2 ) . Oil – in - w a ter (O/W) …. aq u eou s c r eam O/W emulsions are most useful as water-washable bases , whereas w/o e m ul s io n s a re emoll i ent an d clean s in g . 129 6/6/2024 By: Abera J 119

120. Cre a ms… 1 30 Patients often prefer O/W b ecause; C r eam s p r eads m o r e r ead i l y . Is less g r easy Ev apo r a ting w a ter s o othes the inflam ed tiss u e . 6/6/2024 By: Abera J 120

121. C r e a ms… O/ W ( v anishing crea m ) …… Aft e r app lic a tion of the c r eam the w a t e r evaporates leaving behind a thin residue film of the stearic acid. For oozing or weeping surface (wound that release exudates from s k in) ……..because O/W mi x o o zi n g s u r f ac e . Vanishing cream is prepared by incorporation of significant amount of s te a r ic aci d in a n O/W e m ul s io n . Humectants (glycerin, PEG, 7% sorbitol) are frequently added to vanishing creams and O/W emulsions to decrease evaporation of water f r om t he s urface of the ba se . 1 3 1 6/6/2024 By: Abera J 121

122. General compounding procedure for creams Emulsified creams are prepared by heating the components of the oily p h as e u n til molten an d then c o oled . The component of the aqueous phase are mixed in a separate vessel and als o he a t e d to 6 c . The aqueo u s ph ase is t hen adde d t o the oi l y phase a t t he same temperature. 122 6/6/2024 By: Abera J 122

123. General compounding of creams… Th i s is imp o r tant and a the r momete r sh ou l d be us ed . The r es u ltin g e m ul s ion s h o u l d b e sti r r ed u n til coo l . 123 Rapid cooling may result in separation of high melting point components. Excessive aeration caused by vigorous stirring may also lead to a granular product. 6/6/2024 By: Abera J 123

124. General compounding of creams… If necessa r y the p r od uct m a y be ho mogenized aft e r coo lin g . Creams may contain one or more medicaments in solution in one or other of the phas e s . Finally , powdered insoluble medicaments may be dispensed in a cream base 124 6/6/2024 By: Abera J 124

125. Container of Creams Wide-mounthed squat jars may be used for creams where the risk of con tamin a tion in use is con si der ed t o b e mi n imal, e . g . Oils c r eams . The container must be well closed and prevent water evaporation . The mouth of the jar should be covered with a disc of grease proof paper. 125 6/6/2024 By: Abera J 125

126. Container of Creams… Collapsible metal or flexible plastic tubes are to be preferred since these reduce the risk of contamination in use and most proprietary p r oducts a re pa c k ed in t ub e s . 126 6/6/2024 By: Abera J 126

127. Gels (Jellies) Gels are transparent or translucent semi-solid preparations, consisting of solutions or dispersions of one or more AI s in s u ita b l e h yd r op hilic or h yd r op ho bic ba s e s . Semisolid preparations that contain small inorganic particles or large organic molecules interpenetrated by a liquid. 127 6/6/2024 By: Abera J 127

128. Gels (Jellies)… Gels made of inorganic materials are usually two - phase systems where small discrete particles are dispersed throughout the dispersion medium. E . g . Al u mi n um h yd r o xi d e ge l , ben toni te magma When the pa r ticle size of the d is pe r sed p h as e is large r , th e y a re r efe r r ed to as magmas . Gels made of organic molecules are single - phase systems , where no apparent physical boundary is seen between the dispersed phase and the di s pe r si on med i um. ⚫ E. g . Carbo m er and t ragac a nth 6/6/2024 By: Abera J 128

129. Gels (Jellies)… T h e di s pe r si on med i um ; A queous H y d r oalc o h o li c or olea g in o us ba s e Gels are attractive delivery systems ; S i mpl e to ma nufac t u r e S uitable for administering drugs through skin, oral, buccal, ophthalmic, nasal, otic, and vaginal routes P r o v i de intim a te contact bet w een the d r ug and the site of actio n or ab s o r ptio n. 139 6/6/2024 By: Abera J 129

130. Gels (Jellies)… Gels exhibit different physical properties , namely ; imbibition , swelling , syne r esis , an d thix o t r o p y Thixotropy : non - Newtonian flow nature of gels, which is characterized by a r e v e r si b l e g e l - t o – sol ution fo r m a tion wi t h no c hange in v olum e or t e mper a tu r e Imbibition- is the taking up of a certain amount of liquid by a gel without a meas u ra b l e inc r ease in v ol u m e . 1 40 6/6/2024 By: Abera J 130

131. Gels (Jellies)… S w el l ing - is t he taking up of a liq u id b y a g el w ith a n inc r ease in v olum e . Syneresis- Syneresis refers to the contraction or shrinkage of gels as a result of squeezing out of dispersion medium from the gel matrix. Syneresis is a form of instability in aqueous and non aqueous gels 131 6/6/2024 By: Abera J 131

132. Classification and Types of Gels Classification based on the chemical nature Inorganic hydrogels - are usually two phase systems such as aluminum hydroxide gel Organic Gels -are usually single phase systems and may include such gelling agents as Carbomer and Tragacanth and those that contain an organic liq u id, su c h Plastibas e . 132 6/6/2024 By: Abera J 132

133. Classification and Types of Gels … Gels are also classified as hydrogels and organogels based on the physical p r o p e r ties of t he gelling a g ent in the di s pe r si o n . Hydrogels : prepared with water - soluble materials or water - dispersible colloids. E. g. Natural and synthetic gums such as tragacanth, sodium alginate, and pectin 133 6/6/2024 By: Abera J 133

134. Classification and Types of Gels … Organogels (oleaginous gels): prepared using water - insoluble olea g in o us m a te r ials Prepared using water - insoluble lipids such as glycerol esters of fatty acid s , whi c h s w ell in w a ter Eg. Glycerol monooleate, glycerol monopalmito stearete, and glycerol monolinoleate Allows incorporation of both hydrophilic and lipophilic drugs. 6/6/2024 By: Abera J 134

135. Components in gel formulation Gelling agent Gelling a g ent cau s es thi c k eni n g A re either organic hydrocolloids or hydrophilic inorganic substance. They are water dispersible, possess swelling properties , and improve the viscos i ty of di sp e r si o ns 135 6/6/2024 By: Abera J 135

136. Components in gel formulation … An ideal gelling agent Not interact with other formulation components Be f r ee f r om mic r o b ial a t t a c k. Changes in the temperature and pH during preparation and preservation should not alt e r its rheol o g ical p r o p e r tie s . Economic P rovide cooling sensation on the site of application, and possess a pleasant odor. 136 6/6/2024 By: Abera J 136

137. Ex a mpl e s of Gelling Ag e nts Ce t os t e a r yl Alcoh o l Ethylcellulose Guar gum H y d r o xyp r op r yl cellulose Ma g nes ium A l s ilic a te Methylcellulose Povidone Sodi um al g in a te Sodi um star c h g l ycol a te Starch Tragacanth Xantha n gum Acacia Bentonite Carb o xymet h ylc e llul o se Na Colloi d a l silic o n di o xi d e Gelatin Hydroxyethylcellulose Hydroxyproprylmethylcelluose Maltodextrin P o l y v i n yl alco h ol P r o p yl e ne carbo n a te Al g in i c acid 1 1 2 4 . 7 Carbomer 6/6/2024 By: Abera J 137

138. Components in gel formulation … 1 48 Preservatives Methylhydroxybenzoate Propylhydroxybenzoate Hygroscopic agents ( Humectant) Eg. Glycerol, propylene glycol or sorbitol solution. Chelating agents For ingredients which are sensitive to heavy metals. eg . Ethylenediaminetetraacetic acid ( EDTA ) . 6/6/2024 By: Abera J 138

139. Components in gel formulation … Flavours/sweetening agents Included in pharmaceutical gels that are designed for administration into the oral c a vi t y e.g. for the treatment of infection, inflammation or ulceration. Buffers As in other pharmaceutical formulations, buffers (e.g. phosphate, citrate) M ay be included in aqueous & hydroalcoholic-based gels 6/6/2024 By: Abera J 139

140. Ma g m a s Are aqueous suspensions of insoluble, inorganic drugs and differ from ge l s m ai n l y in t ha t t he s u s pended pa r ticles a re large r . When prepared, they are thick and viscous, so no need of a suspending agent. 140 6/6/2024 By: Abera J 140

141. Preparation of Gels and Magmas Generally , the water soluble components are initially dissolved in the v ehicle in a mi x ing v es s el with sti r r in g . The hydrophilic polymer must be added to the stirred mixture slowly to p r e v ent ag g r eg a tion then c o ntin ui n g sti r r ing u n til di s s o luti on of the polymer E xcessive stirring of pharmaceutical gels results in entrapment of air. T h e r efor e , to p r e v ent this t he m i xi n g r a te m u s t n o t be exce s si v e 141 6/6/2024 By: Abera J 141

142. Preparation of Magmas and Gels … By freshly precipitating the disperse phase (chemical rxn) The desired gelatinous precipitate results when solutions of inorganic agents react to form an insoluble chemical having a high a t t ractio n for w a te r . Eg : Milk of magnesia is a preparation containing 7 to 8.5% magnesium hydroxide. 142 6/6/2024 By: Abera J 142

143. Preparation of Magmas and Gels… It ma y be p r epar ed b y a r eac t ion bet w een so di u m h yd r o xi d e and magnes i um s u l f a t e . 2NaOH + MgSO 4 Mg(OH) 2 + Na 2 SO 4 By direct hydration of inorganic chemical in water. Exa m ple : H y dr a tion of Magnesi um o xi d e MgO + H 2 O Mg(OH) 2 143 6/6/2024 By: Abera J 143

144. Uses of Gels (Jel lies) Use ……….. for medication , lubrication and some miscellaneous application Medic a ted J ellies Jellies contain a considerable amount of water and are particularly suitable as vehicle for water–soluble medicaments such as local ane s the t ics , s p e r mic i des , an d anti s eptic s . Lub r icants J ellies Lubricants for glove Miscellaneous jellies Patch testing ……… As a vehicle for allergens applied to the skin to detect sensitivity 144 6/6/2024 By: Abera J 144

145. Examples of Magmas and Gels Bentonite Magma NF S uspending agent Sodium Fluoride and Phosphoric Acid Gel USP dental care prophylactic Fluocinonide Gel USP Anti-inflammatory corticosteroid Tretinoin Gel USP treatment for acne Erythromycin and Benzoyl peroxide Gel Clindamycin Topical Gel Hydroquinone Gel Hyperpigmented skin Salicylic acid Gel keratolytic Desoximethasone Gel anti-inflammatory and antipruritic Aluminum Phosphate Gel ( Amphogel ) USP antacid Aluminum hydroxide Gel USP antacid Dih y d r oxyalu m i nu m A m inoac e tate Magma USP antacid Milk of Magnesia (Magnesia Magma) USP Antacid; laxative 145 6/6/2024 By: Abera J 145

146. C o ntain e rs Containe r s sh ou l d be w el l - filled, to mi n imi z e e v apo r a tion of w a ter into the ai r s pac e , W ell clo s ed an d sto r ed in a cool plac e , to p r e v ent d r ying o u t. 146 6/6/2024 By: Abera J 146

147. THANK YOU. 6/6/2024 By: Abera J 147