topical dermatologic products 18 สค 2015
TRANSCRIPT
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(Semisolid dosage forms for skin) 1
(Semisolid dosage forms for skin)
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0702 362 21 2557
1.
2.
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6.
1.
2.
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4.
1.
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2. (Multiple choice)
1.
2.
Microsoft PowerPoint
1.
2. (Creams)
(emulsifying agents)
w/o creams
o/w creams
o/w w/o creams
1
1 o/w w/o creams
o/w creams w/o creams
oleaginous
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ointment
(
)
o/w creams
oleaginous
ointment
oleaginous ointment
(occlusive effect)
occlusive effect o/w
creams oleaginous
ointment
-
2.1
2.1.1
2.1.2
petrolatum lanolin occlusive effect fatty alcohols
esters 2
2 ( Khar et al., 2013)
Hydrocarbons
Mineral oil (liquid
paraffin)
5-10
Petrolatum
1-2
Polyethylene waxes -
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Microcrystalline
waxes
-
Esters
Vegetable oil
-
Animal fats -
Lanolin -
Isopropyl myristate
Fatty alcohols
Cetyl alcohol 45-52oC
Stearyl alcohol 59-
60oC
hydrocarbons auxiliary
emulsifying agents 10-20 cetyl
alcohol stearyl alcohol cetostearyl alcohol
Fatty acids Stearic acid
69-70oC
1-2
Triethanolamine
Ethers Polyoxypropylene
Mixed Plant waxes
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Animal waxes e.g.
Beeswax
w/o creams
petrolatum lanolin
fatty alcohols esters
fatty alcohols
2.1.3
2 1) Primary emulsifying agents true emulsifying agents
triethanolamine stearate, polysorbate sorbitan
esters
2) Auxilliary emulsifying agents emulsion stabilizers Primary
emulsifying agents auxiliary emulsifying agents
alkyl sulfonate, cetomacrogol polyethylene glycol stearate
1)
(1) (anionic surfactants)
. (Soap) lauric
acid, myristic acid palmitic acid
+1 o/w
creams +1
w/o creams
2
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) Alkaline soap
alkaline soap sodium oleate, potassium laurate sodium stearate
(pH )
(incompatibility)
sodium stearate
oleic acid
) Amine soap
(triethanolamine) stearic acid oleic acid 1:5 triethanolamine vegetable oil triethanolamine 2-4
triethanolamine triethanolamine
triethanolamine
triethanolamine in situsoap
(pH 7.5-8.0)
alkaline soap
in
situsoap
70oC isopropanalamine triethanolamine
triethanolamine stearate o/w creams
Rx Barrier creamsHard paraffin 25 g
Soft paraffin 12 g
Liquid paraffin 3 g
Stearic acid 1.8 g
Triethanolamine 0.7 g
Cetostearyl alcohol 5 g
Chlorocresol 0.2 g
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Purified water qs to 100 g
. Alkyl sulfate
(H2SO4) alkyl sulfate sodium lauryl sulfate, sodium dodecyl benzene sulfate
sodium cetostearyl sulfate o/w creams (pH 7)
pH crystal violet, antazoline hydrochloride
salicylic acid hydrolysis
Sodium lauryl sulfate 0.1-0.5
Alkyl sulfate Rx Emulsifying wax, BP
Sodium lauryl sulfate 10 g
Cetostearyl alcohol 90 g
Purified water 4 mL
. Akyl sulfonate dioctyl sodium sulfosuccinate
o/w wetting agents auxiliary emulsifying agents primary emulsifying agents
(2) (cationic surfactants)
o/w creams
(antiseptic creams)
pH 3-5 carboxymethylcellulose tragacanth
cetrimide, distearyl dimethyl ammonium chloride, cetyl pyrinium chloride,
benzalkonium chloride cetyl trimethyl ammonium chloride
Rx Cetrimide cream, BP
Cetrimide 5 g
Cetostearyl alcohol 50 g
Liquid paraffin 500 g
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Purified water qs to 1000 g
(3) (Amphoteric surfactants)
pH pH
pH
betaines, sulfobetaines, 1,2-
diacyl-L-phosphotidylcholine (lecithin) lauryl sulfobetaine (lauryl sultaine)
(4) (nonionic surfactants)
hydrophilic part alcohol (-OH) ethylene oxide (-OCH2CH2-) lipophilicpart fatty acid, fatty alcohol hydrocarbon HLB
(hydrophilic-lipophilic balance) HLB
o/w creams HLB w/o creams
pH
. Polyalkoxyethers (Polyoxyethylene glycol ethers) Polyoxyethylene
glycol fatty alcohol cetyl alcohol cetostearyl alcohol
parabens
cetomacrogol (Polyoxyethylene glycol monocetyl ether 1000)
fatty alcohol
Rx Cetomacrogol emulsifying wax, BP
Cetomacrogol 1000 200 g
Cetostearyl alcohol 800 g
Polyoxyethylene lauryl ether Brij
. Polyalkoxyesters (Polyoxyethylene glycol esters) polyoxyethylene
glycol o/w creams fatty alcohol
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polyoxyl 40 stearate 40 oxyethylene,
Macrogol stearate 2000 Myrj
. Polysorbate sorbitol ethylene oxide
Polysorbate Tween oxyethylene Polysorbate 20, 40 60 o/w creams
pH
parabens polysorbate paraben paraben
benzyl alcohol ( 2
) brobopol ( 0.2-0.4 ) sorbic acid ( 0.2 ) chlorocresol
( 0.1 ) polysorbate sorbitan ester HLB
. Polalkoxyamide fatty amides ethylene oxide
PEG-8 tallow amide Ethmoid
. Fatty acid ester of polyhydric alcohol polyols
o/w
creams hydrolysis
) Glycerol Glycol esters polyethylene glycol stearate
(stiffening agents) glyceryl monostearate auxiliary
emulsifying agents glyceryl monooleate, diethylene
glycol,monostearate propylene glycol monooleate primary emulsifying
agents ) Sorbitan esters sorbitol sorbitan
esters Span lauric acid, oleic acid, palmitic acid
stearic acid Span w/o creams
pH
Polysorbate Tween o/w w/o creams HLB
. Fatty alcohols auxiliary emulsifying agents
(emollients) w/o creams
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cetyl alcohol, stearyl alcohol, Cremophor A6 Cremophor A25
Cremophor ethoxylated saturated fatty alcohol HLB 15-17
2)
- beeswax w/o creams white wax
beeswax auxiliary emulsifying agents
- wool fat anhydrous lanolin
w/o creams (emollient) auxiliary emulsifying agents
primary emulsifying agents
wool fat
ethylene oxide
polyoxyethylene lanolin derivatives
(emollients) o/w creams- wool alcohol
w/o creams wool fat (hydrous ointment)
wool fat
2.1.4
1) (humectants) (moisturizers)
5
- glycerin 10
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- propylene glycol
- polyethylene glycol 200-600 (PEG)
glycerin glycerin
- sorbitol glycerin 3
2) (thickening agents)
o/w creams o/w creams
colloidal suspension
methylcellulose, carboxy methylcellulose, hydroxyethylcellulose, sodium carboxy methylcellulose carbopol carbopol
0.1-0.3
3) (antioxidants)
- Tocopherol acetate vitamin E
- Butylated hydroxytoluene (BHT) 10 ppm
- Butylated hydroxyanisole (BHA) 0.02
fixed oils 0.1 essential
oils
- Ascorbic acid, isoascorbic acid, ascorbylpalmitate
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- Propyl, octyl, dodecyl esters of gallic acid 0.001
fixed oils 0.1
essential oils
- Sodium metabisulfite, sodium sulfite, sodium bisulfite, sodium thiosulfate- Chelating agents EDTA
- Thioglycerol
- Cystein hydrochloride
4) (preservatives) pH
log P log P
-p-Hydroxy benzoates (parabens)
pH
propylene glycol Polysorbate methyl paraben, propyl paraben butyl paraben
0.01-0.50 methyl paraben propyl paraben
methyl paraben 0.18 propyl paraben 0.02
- Alcohols ethanol 70 , isopropyl alcohol,
chlorobutanol, p-chlorophenyl propanediol (bronopol) 0.01-0.20
benzyl alcohol 2-3 ethanol isopropyl alcohol
- Acids benzoic acid, sorbic acid propionic acid
0.1-0.2
- Mercurials phenyl mercuric acetate
borate
thimerosol 0.1-0.2
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3 HLB (: Ansels Pharmaceutical dosage
forms and drug delivery systems, 2011)
HLB 1-3
3-6 w/o
7-9 (wetting agents)
8-16 o/w
13-15 (detergents)
15-18 (solubilizing agents)
4 HLB (: The HLB system
a time-saving guide to emulsifier selection, 1984)
HLB
1-4
3-6
6-8
8-10
10-13
>13
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5 HLB (: Ansels Pharmaceutical dosage forms and
drug delivery systems, 2011)
HLB HLBEthylene glycol distearate 1.5 Triton X-45 10.4
Sorbitan tristearate (Span65) 2.1 Methylcellulose 10.5
Propylene glycol monostearate 3.4 Polyoxyethylene monostearate (Myrj
45)
11.1
Triton X-15 3.6 Triethanolamine oleate 12.0
Sorbitan monooleate (Span80) 4.3 Tragacanth 13.2
Sorbitan monostearate (Span60) 4.7 Triton X-100 13.5
Diethylene glycol monolaurate 6.1 Polysorbate 60 (Tween60) 14.9
Sorbitan monopalmitate (Span40) 6.7 Polysorbate 80 (Tween80) 15.0
Sucrose dioleate 7.1 Polysorbate 20 (Tween20) 16.7
Acacia 8.0 Plurinic F 68 17.0
Amercol L-101 8.0 Sodium oleate 18.0
Polyoxyethylene lauryl ether (Brij
30)
9.7 Potassium oleate 20.0
Gelatin 9.8 Sodium lauryl sulfate 40.0
2.2.1 HLB
1 HLB (required HLB)
HLB 62
3 HLB
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6 HLB (required HLB of oil phase) (: The HLB
system a time-saving guide to emulsifier selection, 1984 Aultons pharmaceutics the
design and manufacture of medicines, 2007)
HLB
w/o o/w
Stearic acid - 17
Cetyl alcohol - 15
Stearyl alcohol - 14
Lanolin, anhydrous 8 10
Cotton seed oil - 7.5
Mineral oil, light (liquid paraffin) 4 10-12
Castor oil - 14
Hard paraffin 4 10
Beeswax 5 9.5
Petrolatum 5 12
1
Rx Liquid paraffin 35%
Lanolin, anhydrous 1%
Stearyl alcohol 1 %
Cetyl alcohol 1%
Glycerin 5%
Emulsifying agents 7%Purified water qs to 100%
1) HLB
liquid paraffin, lanolin, stearyl alcohol
cetyl alcohol
1.1 = 35+1+1+1 = 38%
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Liquid paraffin (35x100)/38 = 92.11 %
Lanolin, anhydrous (1x100)/38 = 2.63%
Stearyl alcohol (1x100)/38 = 2.63%
Cetyl alcohol (1x100)/38 = 2.63%1.2 HLB HLB
6
Liquid paraffin (92.11/100) x 12 = 11.05
Lanolin, anhydrous (2.63/100) x 10 = 0.263
Stearyl alcohol (2.63/100) x 14 = 0.37
Cetyl alcohol (2.63/100) x 15 = 0.39Total = 12.073
HLB = 12.073
2)
2 HLB Span60 (HLB = 4.7) Tween40 (HLB = 15.6)
HLB = 12.073 a Span60
1-a Tween40
12.073 = (a x 4.7) + (1-a)(15.6)
12.073 = 4.7a + 15.6 15.6a
10.9a = 3.527
a = 0.324 Span60 0.324 32.4% Tween40 0.676 (1-0.324) 67.6%
HLB = 12.073
3)
7%
Span60 = (32.4/100) x 7 = 2.268 g
Tween40 = (67.6/100) x 7 = 4.732 g
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Rx Liquid paraffin 35%
Lanolin, anhydrous 1%
Stearyl alcohol 1%
Cetyl alcohol 1%Span 60 2.268%
Tween 60 4.732%
Purified water qs to 100%
2.2.2 2
1) Beaker method (conventional hot method)
(1)
(2) water bath (1)
72-75oC
75-78oC
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1beaker method
(3)
(Phase inversion) o/w creams
w/o
cream o/w
creams
(4) 40-45oC
wool fat, wool alcohol cholesterol
beaker method
water bath hot plate homogenizer
( 2)
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Toothed colloid mill (3)
jacketed (4)
2 (:http://www.alibaba.com/product-detail/Laboratory-
Homogenizer_500027937.html)
3Toothed colloid mill (: http://www.frymakoruma-us.com/products/detail/toothed-colloid-mill-type-mz)
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4 (: http://www.fong-hwang.com/category/emulsifier-homogenizer-machine.htm)
2) Incorporationmethod (non-thermal method)
slab spatula
(levigate) geometric dilution
(levigating agents) glycerin mineral
oil
(emollient)
(stiffening agents)
Beaker method
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2.3 5
2.3.1 Creaming
2.3.2 Flocculation
creaming creaming flocculation
coalescence
creaming flocculation
flocculation
2.3.3 Coalescence
auxiliary emulsifying agents
2.3.4 Sedimentation
2.3.5 Phase inversion o/w w/o w/o
o/w 2.3.6 Oswald ripening
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5 (: http://imgarcade.com/1/types-of-emulsion/)
2.4
Rx Vanishing cream
Stearic acid 15 g Stiffening agent,emulsifying agent
White wax 2 g EmollientWhite petrolatum 8 g Emollient
Triethanolamine 1.5 g Emulsifying agent
Propylene glycol 5 g Humectant
Purified water qs to 100 g Water phase
Rx Salicylic acid and sulfur cream, BP
Salicylic acid 20 g Active ingredient
Precipitated sulfur 20 g Active ingredient
Aqueous cream qs to 1000 g Base
Rx Aqueous creams, BP
Emulsifying ointment 300 g Base
Chlorocresol 1 g Active ingredient
Purified water 699 g Water phase
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Rx Mineral oil base cream
Cetyl alcohol 20 g Stiffening agent
Mineral oil 20 g Emollient
Tween 80 4.5 g Emulsifying agent, water phaseSpan 80 0.5 g Emulsifying agent, oil phase
Propyl paraben 0.08 g Preservative
Methyl paraben 0.4 g Preservative
Purified water qs to 100 g Water phase
Rx Nonionic cream base
Cetyl alcohol 5 g Stiffening agentStearyl alcohol 5 g Stiffening agent
Glyceryl monostearate 2 g Auxilliary emulsifying agent
Petrolatum 2 g Emollient
Liquid paraffin 5 g Emollient
Cetomacrogol 1000 3 g Emulsifying agent
Glycerin 5 g HumectantPurified water qs to 100 g Water phase
Rx Zinc cream, BP
Zinc oxide 320 g Active ingredient
Calcium hydroxide 0.45 g Emulsifying agent
Oleic acid 5 mL Emulsifying agent
Arachis oil 320 g emollientWool fat 80 g Auxilliary emulsifying agent
Purified water qs to 1000 g Water phase
Rx Cold cream, USP
Spermaceti 12.8 g Stiffening agent
White wax 12 g Emollient, Emulsifying agent
Liquid paraffin, light 56 g Emollient
Sodium borate 0.5 g Emulsifying agent
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Purified water qs to 1000 g Water phase
cerotic acid white wax sodium
borate in situsoap
Rx Anionic cream baseStearyl alcohol 5 g Stiffening agent
Cetyl alcohol 5 g Stiffening agent
Sodium lauryl sulfate 1 g Emulsifying agent
Liquid paraffin 5 g Emollient
Glycerin 5 g Humectant
Paraben concentrate 5 g PreservativeGlyceryl monostearate 2 g Auxilliary emulsifying agent
Petrolatum 2 g Emollient
Purified water qs to 100 g Water phase
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3. (Lotions)
(Newtonian)
Non-newtonian
3
3.1
glycerin
propylene glycol Salicylic acid lotion,
betamethasone valerate lotion, Whitfields lotion Minoxidil solution
Saicylic acid lotion keratolytic agent
Rx Salicylic acid 3 g
95% ethanol 25 mL
Purified water 25 mL
Propylene glycol qs to 100 mL
Whitfields lotion Rx Benzoic acid 5 g
Salicylic acid 3 g
95% ethanol qs to 100 mL
Minoxidil solution
Rx Minoxidil 5 g
95% ethanol 30 mL
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Propylene glycol 50 mL
Isopropyl myristate 1 mL
Purified water qs to 100 mL
3.2
(suspending agents)
1)
carbomer, carboxy methylcellulose (CMC), bentonite methylcellulose
acacia tragacanth
2) (humectants)
propylene glycol, glycerin
polyethylene glycol 400
(homogenizer)
(caking)
Calamine lotion USP
Benzoyl peroxide lotion
3.3
o/w w/o emulsion Beaker method
70-73oC 73-75oC
(phase inversion)
40-45oC
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Benzoyl benzoate lot ion, USP,
Clotrimazole lotion Basic lotion
Benzoyl benzoate lotion, USP
Rx Benzyl benzoate 250 g Active ingredient ()Triethanolamine 5 g emulsifying agent
Oleaic acid 20 g emulsifying agent
Purified water qs to 1000 g water phase
oleaic acid tr iethanolamine
triethanolamineoleate o/w oleaic acid triethanolamine
benzyl benzoate 250 mL
Basic lotion (o/w lotion)
Rx Mineral oil 10 mL emollient, oil phase
Stearic acid 3 g emulsifying agent
Triethanolamine 1 mL emulsifying agent
Lanolin 1 g emollient, oil phaseColor qs color
Purified water 75 mL water phase
stearic acid triethanolamine
triethanolaminestearate o/w
Clotrimazole lotion
Rx Clotrimazole 40 g antifungalWhite petrolatum 50 g emollient, oil phase
Mineral oil 60 g emollient, oil phase
Cetyl alcohol 72 g emollient, oil phase
Cetheth-20 22.5 g emulsifying agent, oil phase
Benzyl alcohol 10 g preservative, water phase
Propylene glycol 100 g humectant, water phase
Na2HPO4 0.35 g buffer, water phase
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NaH2PO4 5 g buffer, water phase
Purified water qs to 1000 g water phase
Cetheth-20 HLB 15.7
o/w lotion Cetheth-20 (1.1 g) (160g) clotrimazole ( Cetheth-
20 clotrimazole)
25-30oC
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4. (Ointments)
(mucous membrane)
(single-phase) (base)
4.1
2
1) (Medicated ointments)
2)
(Unmedicated ointments)
4
1) (Oleaginous/hydrocarbon bases)
(vegetable oils) (silicones)
(synthetic esters) (occlusive effect)
petrolatum, white petrolatum, white ointment,
yellow ointment, beeswax, spermaceti, mineral oil, paraffin silicones -
Petrolatum, USP yellow petrolatum soft paraffin petrolatum jelly
Vaseline
petrolatum
(white petrolatum)
petrolatum
pH
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38-60oC petrolatum
6
6 petrolatum
- Yellow ointment, USP
Yellow wax 50 gPetrolatum 950 g
Yellow wax Apis mellifera petrolatum
yellow wax casserole water bath petrolatum
(congeal)
- White ointment, USP
White wax 50 gWhite petrolatum 950 g
To make 1000 g
White wax yellow wax
petrolatum
white wax petrolatum casserole water bath
-
Mineral oil liquid paraffin liquid petrolatum paraffin oil
heavy mineral oil, USP
0.848-0.905 light mineral oil, NF 0.818-0.880
light mineral oil
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mineral oil
- Soft petrolatum
White petrolatum 90%Mineral oil, NF 10%
mineral oil
- Gelled petrolatum
White petrolatum 75%
Mineral oil, NF 25% mineral oil
- Paraffin hard paraffin paraffin wax
47-65oC
(stiffening agents) paraffin 7
7 paraffin
- Silicones dimethicone, methylphenylpolysiloxane cyclomethicone
mineral oil
(water repellant properties)
- mono- di- tri-glyceride
(peanut oil) (almond oil) (sesame oil)
(olive oil)
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(antioxidants) (chelating agent)
(fatty alcohol) - Beeswax Apis mellifera
white wax 62-65oC (thickening
agent) white wax 8
8 white wax
- Spermaceti 44-52oC
spermaceti 9
9 spermaceti
2) (Absorption bases)
(w/o emulsifiers) wool fat, wool alcohol, cholesterol, sorbitan ester
2
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(1) (anhydrous forms)
(w/o)
hydrophilic petrolatum, lanolin (anhydrous), simple ointment, aquabase ointment wool alcohol ointment
- Hydrophilic petrolatum, USP
Cholesterol 30 g
Stearyl alcohol 30 g
White wax 80 g
White petrolatum 860 g- Lanolin, USP (anhydrous)
wool fat
( 0.25)
30-50 36-42oC Modified lanolin, USP
lanolin (anhydrous) lanolin alcohol
lanolin 10 lanolin
10 lanolin
- Simple ointment, BP
Wool fat 50 g
Paraffin 50 g
Cetostearyl alcohol 50 g
Petrolatum 850 g
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- Aquabase ointment
Cholesterol 30 g
Cotton seed oil 30 g
White petrolatum 940 g- Wool alcohol ointment, BP
Wool alcohol 6 g
Paraffin 17 g
White petrolatum 17 g
Liquid paraffin 60 g
(2) (hydrous forms) (w/o) lanolin (hydrous)
cold cream base
- Lanolin (hydrous) lanolin absorption base
Lanolin alcohol 10%
Lanolin 25%
Mineral oil, light 30%Purified water 35%
Mineral oil
(w/o) glyceryl monosterate, cholesterol, cetyl
alcohol sorbitan fatty acid
- Cold cream base
Borax 1.00%Mineral oil, light 50.00%
Synthetic beeswax flakes 13.00%
Glyceryl monostearate, pure 1.00%
Methyl paraben 0.25%
Propyl paraben 0.15%
Purified water 34.60%
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Cold cream base
3)
(Water-removable bases) (o/w) water-washable base
vanishing cream hydrophilic ointment, USP
- Vanishing cream
Stearic acid 13%
Stearyl alcohol 1%
Cetyl alcohol 1%
Glycerin 10%
Potassium hydroxide 0.9%
Methyl paraben 0.1%
Propyl paraben 0.05%
Purified water qs to 100%
- Hydrophilic ointment, USP
Sodium lauryl sulfate 10 g
Propylene glycol 120 g
Stearyl alcohol 250 g
White petrolatum 250 g
Methyl paraben 0.25 g
Propyl paraben 0.15 gPurified water 370 g
beaker method propylene glycol,
purified water, methyl paraben propyl paraben 78oC
sodium lauryl sulfate, white petrolatum stearyl alcohol
75oC
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4) (Water-soluble bases)
polyethylene glycol (PEG)
ointment, bentonite, gelatin, veegum - PEG ointment, NF
PEG 3350 400 g
PEG 400 600 g
PEG ethylene oxide
PEG 600 PEG
600-1000 PEG 1000 (wax) PEG
(w/o) paraben, phenol
polythene bake lite
PEG fatty
alcohol stearyl alcohol 5 20- bentonite, gelatin, veegum
- Universal ointment base
Veegum 10 gSodium lauryl sulfate 0.1 g
Methyl paraben 0.1 g
Glycerin 10 g
Tween 80 1 g
Purified water 78.8 g
- Bentonite ointment base
Bentonite 20 g
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(Semisolid dosage forms for skin) 38
Sodium lauryl sulfate 0.5 g
Glycerin 10 g
Purified water 69.5 g
4 7
7 ( Premjeet et al., 2012)
/
1. ,
PEG ointment
2.
3.
4.
5.
-
6.
7.
8.
9.
10.
White ointment,
white petrolatum
Aquabase, Polysorb,
Eucerin (aquaphor)
Unibase,
Velvachol,
Dermabase
Polybase
-
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(Semisolid dosage forms for skin) 39
4.2
1)
2)
3)
4)
5)
6)
4.3
1)
2)
3)
4)
5)
6)
7)
4.4
4.4.1 (active ingredients)
4.4.2 (ointment bases)
4.4.3
(additives) 1)
Fatty acids fatty alcohol stearic acid, stearyl alcohol, cetyl alcohol
cetostearyl alcohol soft
paraffin PEG
2) (Synthesis ester of fatty acid) isopropyl
myristate (IPM), isopropyl stearate isopropyl palmitate
IPM
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isopropyl stearate IPM isopropyl palmitate
IPM
4.4.4
(antioxidants) sodium sulfate, sodium metabisulfite ascorbic acid
4.4.5 (rancids)
butylate hydroxytoluene (BHT), beta hydroxy acid (BHA), tocopherol
propylgallate
4.4.6 (chelating agents)
citric acid, maleic acid, tartaric acid disodium EDTA
4.4.7 (thickening agents)
bentonite, sodium alginate, methylcellulose,
sodium carboxymethylcellulose carbomer
4.4.8 (preservatives)
methyl paraben, propyl paraben, butyl paraben, sorbicacid, benzyl alcohol benzoic acid
4.4.9 (humectants)
2-10
glycerin,propylene glycol, sorbitol PEG
4.4.10 (buffers) -
citric acid, phosphoric acid sodium
phosphate
4.4.11 (coloring agents odoring agents)
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4.5 2
4.5.1 (Incorporation)
/
slab (11) spatula spatula
spatula
(rubber) spatula 12 13
(ointment mill)
geometric dilution
11 Slab
12 spatula
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13 spatula
(levigating agents)
mineral oil glycerin
- Compound benzoic acid ointment, BP
Benzoic acid, in fine powder 60 g
Salicylic acid, in fine powder 30 g
Emulsifying ointment, BP 910 g
To make 1000 g
Emulsifying ointment, BP
Emulsifying wax, BP 300 g
White soft paraffin 500 g
Liquid paraffin 200 g
To make 1000 g
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benzoic acid salicylic acid
emulsifying ointment
geometric dilution slab spatula (rubber) mineral oil
-
Zinc and castor oil ointment, BP Zinc oxide 75 g
Castor oil 500 g
Arachis oil (peanut oil) 305 g
Cetostearyl alcohol 20 g
White beeswax 100 g
castor oil, arachis oil, cetostearyl alcohol white beeswax castor oil
zinc oxide geometric dilution slab
spatula
4.5.2 (Fusion)
ointment mill
(porcelain
dish) casserole (steam jacketed kettles)
(direct heat) water bath (indirect heat)
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(Semisolid dosage forms for skin) 44
beaker method
beeswax, paraffin, stearyl alcohol PEG
-Methyl salicylate ointment Methyl salicylate 500 g
Cajuput oil 25 g
Cineole 25 g
Purified water 45 g
Menthol 100 g
Wool fat 105 gWhite beeswax 200 g
To make 1000 g
white beeswax wool fat
menthol methyl salicylate cajuput oil cineole
-
Compound methyl salicylate ointment
Methyl salicylate 250 g
Menthol 50 g
Eucalyptus oil 50 g
Wool fat 100 g
Vaseline 80 g
Hard paraffin 100 g
-
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(Semisolid dosage forms for skin) 45
White beeswax 100 g
wool fat, vaseline, hard paraffin white beeswax
menthol methyl salicylate eucalyptus oil
-
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(Semisolid dosage forms for skin) 46
5. (Pastes)
Pastes
20-50
70-80 m
5.1 2
5.1.1 Oily and fatty pastes
(oleaginous bases)
Coal tar paste, BPC
soft paraffin Compound aluminium paste, BPC liquid paraffin
white petrolatum, lanolin (anhydrous) white wax
- RxZinc oxide paste, USP
Zinc oxide 25 g Active ingredient
Starch 25 g Active ingredientWhite petrolatum 100 g Base
- RxZinc oxide with salicylic acid, NF
Salicylic acid, in fine powder 20 g Active ingredient
Zinc oxide paste qs to 1000 g Base
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- RxCompound Zinc oxide paste
Zinc oxide 60 g Active ingredient
Coal tar 60 g Active ingredient
Starch 380 g Active ingredientLanolin 50 g Base
Hard paraffin 50 g Base
White soft paraffin 400 g Base
- RxSalicylic acid paste
Salicylic acid 3.4 g Active ingredient
Glycerin 5 g HumectantZinc oxide, fine powder 25 g Active ingredient
Starch 25 g Active ingredient
White soft paraffin qs to 100 g Base
5.1.2 Water soluble gels glycerogelatins
emulsifying ointment base emulsifying wax
tragacanth, pectin, alginates, boroglycerin, methylcellulose sodium methylcellulose
Zinc and Coal tar paste, BPC emulsifying wax
Titanium dioxide paste, BPC glycerin
- RxZinc gelatin, USP (glycerogelatin bases)
Zinc oxide 100 g Active ingredient
Gelatin 150 g BaseGlycerin 400 g Base
Purified water 350 g Base
- Rx Magnesium sulfate paste, BP (glycerogelatin bases)
Dried MgSO4 45 g Active ingredient
Phenol 0.5 g Active ingredient
Glycerin 55 g Base
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MgSO4 150oC 1.5
glycerin 120oC 1
phenol dried MgSO4
- Rx Recorcinol and sulphor paste, BPResorcinol 50 g Active ingredient
Precipitated sulphor 50 g Active ingredient
Zinc oxide 400 g Active ingredient
Emulsifying ointment 500 g Base
5.2
(Incorporation)
5.2.1
5.2.2
1)
geometric dilution 1
geometric dilution
2)
lanolin (anhydrous)
(levigating
agents)
slab
spatula ointment mill
roller mill
-
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(Semisolid dosage forms for skin) 49
6. (Gels)
(small inorganic molecules)
(large organic molecules)
Thixotropic
6.1
6.1.1 2
1) Inorganic gels two-phase gels
Lyophobic solvent/medium hating
two-phase
inorganic gels aluminium hydroxide gel floccule
magma milk bentonite magma, bismuth magma magnesium magma
2) Organic gels single-phase gels
Van der Waal
boundary (dispersed
molecule) (disperse medium) Lyophlilic
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solvent/medium loving
6.1.2 2 1) (Medicated gel)
antiseptic gels NSAIDs gels
2) (Lubricant gel)
Lignocaine gel
6.1.3 2
1) (Covalent)
2) (Noncovalent)
- Physical gelatin- Coulumbic interaction
(electrostatic interaction)
- Hydrogen bonding
- Coordinate bonding
- Hydrophobic bonding
6.1.4 2 1) Hydrogels aqueous gels
2) Organogels
polyethylene glycol (low molecular weight) mineral oil metallic stearate
-
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(Semisolid dosage forms for skin) 51
6.2
6.2.1 (active ingredients)
6.2.2 (gelling agents)
(gelation gel formation) pH
gel point gelatin
30oC
pH
1) 2 polysaccharides
(1) Polysaccharides 0.5-40
- tragacanth bassarin 60-70
tragacanth 30-40
pH 4-8 tragacanth parabens parabens
parabens methyl paraben 0.22-0.26 propyl paraben 0.05
tragacanth
tragacanth ethanol,
glycerin propylene glycol tragacanth tragacanth 2-3
5
Rx Tragacanth 5 g
Alcohol 10 g
Glycerin 2 g
Purified water qs to 100 g
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- acacia tragacanth
acacia
- Alginic acid 5-10
200-300 alginic acid
alginic acid
30
- Sodium alginate alginic acid
1.5-2.0 5-10 pH 4-10 pH 3 sodium alginate
1 24
sodium alginate 1
sodium alginate
sodium alginate
calcium gluconate, calcium tartate calcium citrate sodium
alginate
(2)
- gelatin 2-15
gelatin
- pectin sodium carboxymethyl
cellulose gelatin
pectin
2)
-
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- Methylcellulose (MC) non-ionic cellulose 5
methylcellulose 450, 2500 4500
centistroke 20 2 MC
MC 90oC (1 3 ) MC 2 3
3-4 propylene glycol
MC MC parabens
parabens
- Carboxymethylcellulose (CMC) 4-6
pH pH = 2 pH 2-10 pH 7-9
- Sodium carboxymethylcellulose (SCMC)
SCMC 25-50 (25-50 centistroke), SCMC 400-600 (400-600
centistroke) SCMC 1500 (1500 centistroke)
methylcellulose 1.5-5
SCMC pH 1-20 pH MC
pH 5-10 NH4+
Al3+ Fe3+ SCMC
glycerin propylene glycol
SCMC
- Hydroxypropyl methylcellulose (HPMC, Hypromellose) Hypromellose 20, 50, 125, 450, 1500 4500
polyethylene glycol
2 pH 3-10 (50-90oC)
- Hydroxyethyl cellulose (HEC) non-ionic ether
-
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(Semisolid dosage forms for skin) 54
3)
(1) (ionic substances)
glycerin
triethanolamine NaOH pH 6-11 0.1-1.0
0.5-5.0 Carbomer
- Carbomer carboxy polymethylene
0.3-1.0 0.5-5.0
carbomer carbomer
benzoic acid, sodium benzoate
benzalkonium chloride carbomer carbomer 910,
carbomer 934, carbomer 940 carbomer 1342
carbomer ()
carbomer (lump) carbomer
carboxyl groups carbomer carbomer
pH 4.5-11 pH 7 carbomer
20 NaOH KOH
50 triethanolamine carbomer
EDTA
(2) (nonionic substances)
-
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- Povidone Polyvinyl pyrrolodone 10
4) - Veegum 10
pH 3.5
Veegum
24
- Bentonite 8-10
Veegum
- Polyvinyl alcohol
100oC
polyvinyl alcohol 2.5
polyvinyl alcohol 30,000 , 130,000
200,000 polyvinyl alcohol
6.2.3
1) (preservatives)
88 (: Premjeet et al., 2012)
Tragacanth Methyl paraben 0.2% w/v propyl paraben 0.05% w/v
Sodium alginate Methyl paraben 0.1-0.2% w/v, chlorocresol 0.1% w/v, benzoic acid 0.2% w/v
Pectin Benzoic acid 0.2% w/v, methyl paraben 0.12% w/v, chlorocresol 0.1-0.2% w/v
Methylcellulose Phenylmercuric nitrate 0.001% w/v, benzalkonium chloride solution 0.02% v/v
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SCMC, HPMC Methyl paraben 0.2% w/v propyl paraben 0.02% w/v
Carbomer Methyl paraben 0.15% w/ v propyl paraben 0.05% w/v
2) (humectants)
glycerin, propylene glycol sorbitol
3) (dispersing agents wetting agents)
2
propylene glycol, glycerin
HLB 7-9
4) (permeation enhancers)
Stratum
corneum
Tween20, sodium lauryl sulfate, glycerin, dimethyl sulfoxide, N-methyl-2-pyrrolidone
dimethyl formamide
5) (stabilizers) (chelating agents)
EDTA
6.3
6.3.1 (gel base)
lumping
(homogenizer)
6.3.2
-
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-
-
-
-
glycerin, propylene glycol
6.3.3
6.4
6.4.1 (Non-homogeneous)
6.4.2
6.4.3 carbomer
6.4.4 (Lumping)
-
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(Semisolid dosage forms for skin) 58
6.4.5
Syneresis pectin, sodium alginate
6.5
-RxLubricant gel
Sodium carboxymethylcellulose 5.0 g gelling agent
Glycerin 15 g wetting agent, humectant
Methyl paraben 0.1 g preservative
Brilliant blue 0.001 g coloring agentPurified water qs to 100 g dispersing medium
-Rx Alcohol gel
Carbomer 940 0.25 g gelling agent
Ethanol 70 mL Antiseptic
Glycerin 1.0 mL wetting agent, humectant
Triethanolamine 1-2 drop pH adjustmentBrilliant blue qs coloring agent
Purified water qs to 100 mL dispersing medium
-Rx Sodium alginate gel
Sodium alginate 7 g gelling agent
Glycerin 7 g wetting agent, humectant
Methyl paraben 0.2 g preservativeCalcium gluconate 0.05 g Viscositing agent
Purified water qs to 100 g dispersing medium
-Rx Ephedrine sulphate gel
Ephedrine sulphate 1 g active ingredient
Carbomer 934 2 g gelling agent
Triethanolamine 1.65 mL pH adjustment
Purified water qs to 100 mL dispersing medium
-
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(Semisolid dosage forms for skin) 59
-Rx Bentonite gel
Zinc oxide 10 g active ingredient
Glycerin 10 g wetting agent, humectants
Purified water qs to 100 g dispersing medium-Rx Zinc gelatin, USP
Zinc oxide 100 g active ingredient
Gelatin 150 g gelling agent
Glycerin 400 g wetting agent, humectants
Purified water 350 g dispersing medium
-Rx Flucinolone acetonide gel ( )Flucinolone acetonide 0.18 g active ingredient
Ethanol, 95% 1.82 mL cosolvent
Propylene glycol 45.45 mL wetting agent, humectants
Polyethylene glycol 400 36.36 mL wetting agent, humectants
Paraben concentrate 1.82 mL preservative
Carboxymethylcellulose 4.36 g gelling agentHot water qs to 100 mL dispersing medium
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7. (Emulsiongels)
thixotrophy
Voltaren emulgel ( 14)
Piroxicam emulsiongel
14
-RxPiroxicam emulsiongel
Piroxicam 0.5% NASIDs
Polyethylene glycol 400 19.5% cosolvent for piroxicam
Ethanol 10% cosolvent for piroxicam
Propylene glycol 10% cosolvent for piroxicam
Cream base 30%
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Cetyl alcohol 20 g stiffening agent
Mineral oil 20 g emollient
Span 80 0.5 g emulsifying agent
Tween 80 4.5 g emulsifying agentParaben concentrate 1 g preservative
Purified water qs to 100 g water phase
Gel base 30%
Carbomer 934 1 g gelling agent
Glycerin 5 g wetting agent, humectant
Paraben concentrate 1 g preservativeTriethanolamine qs to pH 7.0 pH adjustment
Purified water qs to 100 g dispersing medium
7.1
1)
2)
3)
4)
5) (permeation enhancer)
6)
7)
8)
7.2
1)
2) beaker method
3)
geometric dilution
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4) 3)
geometric dilution
5)
-
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8. (Liniments)
3
8.1
Camphor and Soap Liniments
NF
8.2 Methyl salicylate Liniment Compound methyl salicylate Liniment
8.3 (soap)
Turpine Liniment BP soft soap, camphor, turpine oil
9.
w/o
o/w
-
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(Semisolid dosage forms for skin) 64
1.
2.
3. HLB 4. Humectants
5.
6.
7.
8.
. . 2558. ; .
Allen LV, Popovich NG, Ansel HC. Ansels pharmaceutical dosage forms and drug delivery
systems. 2011. 9thed: Wolters Klumar; China.
Aulton ME. Aultons pharmaceutics the design and manufacture of medicines. 2007. 3rded:
Churchill Livingstone; London.British Pharmacopoeia.Stationery office Dublin. 2013
The HLB system. ICI Americas, Inc. 1984.
Khar RK, Vyas SP, Ahmad FJ, Jain GK. The Theory and practice of industrial pharmacy. 2013.
4thed: CBS Publishers and Distributors Pvt Ltd; India.
Mathur V, Satrawala Y, Rajput MS. Physical and chemical penetration enhancers in
transdermal drug delivery system. Asian Journal of Pharmaceutics 2010, 4: 173-183.
Pharmacopeial Forum in the United States Pharmacopeial Convention, Inc. Topical and
transdermal drug products. Vol. 35(3) [May-June 2009]
Premjeet S, Ajay B, Sunil K, Bhawana K, Sahil K, Divashish R, Sudeep B. Additives in topical
dosage forms. International Journal of Pharmaceutical, Chemical and Biological
Sciences 2012, 2(1): 78-96.
Troy DB, editor. Remington the science and practice pharmacy.2006.21thed: Lippincott
Williams and Wilkins;Marylands.
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United States Pharmacopoeia 32-National Formulary 27.2009. Pharmacopeial Convention;
Rockville, MD: U.S.
Walters KA. Dermatological and transdermal formulation. 2002. CRC Press taylor and Francis
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