User:Alattar
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Ointment and Creams
Ointment is a semi solid preparation containing medical agents uniformly dispersed in a fatty base. Our earliest records of the use of various fats and oil date back to the Babylon-Assyria about 3000 – 5000 B.C. Creams, which are usually described as semi solid preparations less viscous than ointment.
Ointments and Creams serving as vehicles for topical application of medicinal substances, they also used as emollient for skin and as protective of skin.
Anatomy of Skin
Generally, Skin described in terms of three tissue layers : epidermis , dermis and subcutaneous fat layer. The epidermis, is the external layer of the skin, varying in thickness from 0.16 mm on the eye lids to 0.8 mm on the palms and soles. Epidermis subdivided in to five layers, starting from outer, they are as follows :
1- Stratum Corneum ( Horny Layer) 2- Stratum Lucidum ( Barrier Zone) 3- Stratum Granulosum ( Granular Layer) 4- Stratum Spinosum ( Prickle cell layer) 5- Stratum Germinatium (Basal cell layer)
The horny layer ( Stratum Corneum) is thickest on the soles of the feet and is much thinner on the eye lids. There is a thin surface film of emulsified lipids covering the Stratum Corneum. This protective film usually has a PH 4.5 – 6.5 , so called acid mantle of skin , its derived from lactic acid and dicarboxylic amino acids in sweat secretion, mixed with sebaceous lipoidal substances ( cholesterol).
Precutaneous Absorption
The skin offers greater resistance to penetration by drug substances than do mucous membrane, the mucous membrane in the rectal absorbed 26% - 29% of the steroid, as compared to only 2% penetration through the skin. The keratin content in the mucous membrane is relatively low or may even be absent. Drugs may be diffuse through the skin by three different routes : the hair follicle region, the sweat gland ducts, and intact Stratum Corneum.
Factors influencing absorption through skin
1- Partition Co-efficient of drug . Substances possessing both water and lipid solubility are favorable absorbed through the skin. some studies indicate that those substances with an ether : water partition coefficient greater than 1 show optimal penetration of the skin.
2- Moisture and Temperature in the environment of skin. Humidity and /or temperature show to have influence on the absorption of substances through the skin . A ten-fold increase in the skin penetration of acetylsalicylic acid and glucosteroids was obtained when the environment temperature was raised from 10 Co to 37 Co . a similar increase in penetration was noted for these substances when they were applied to completely hydrated skin as compared to skin at environmental humidity of 50%.
3- Pathologic injury to the skin. Injury to the skin which disrupt Stratum Corneum , result in increased skin permeability. Increase blood vessels dilation may result in enhanced permeability of local capillaries. Erythema due to mild thermal burns will increase the absorption, but sever burns enough to result in protein denaturation and cellular destruction and decrease absorption. Chemical injury of the skin barrier by strong alkalis, acids and hydrogen sulfide gas result in increased permeability. When the skin is defatted by organic liquids, the barrier function is disrupted and penetration is more rapid.
4- Vehicle Skin penetration of drug can be increased by the use of suitable vehicle. ethanol penetrates faster in olive oil than normal saline. Substances that have a lower solubility in the vehicle are released more readily. The PH of vehicle also can influence the rate of release of the drug, thus for acidic substances, the activity changes rapidly when the PH of vehicle is greater than the Pka of substances. Similarly for basic substances, the activity is influenced when the PH of vehicle is less than Pkab of the drug.
* Classification of Bases *
Ointments can classified according to type of base in to :
I . Oleaginous Ointment Base
1- Anhydrous 2- Dose not absorb water readily 3- Insoluble in water 4- Not water removable
II . Absorption Ointment Base
1- Anhydrous 2- Absorb water 3- Insoluble in water 4- Not water removable
III . Emulsion Ointment Base
A- Emulsion Ointment base W/O 1- Hydrous 2- Absorb water 3- Insoluble in water 4- Not water removable B- Emulsion Ointment base O/W a. Hydrous b. Absorb water c. Insoluble in water d. Water removable
IV . Water Soluble Ointment Base
1- Anhydrous 2- Absorb water 3- Soluble in water 4- Water removable
1- Oleaginous ( Hydrocarbon) bases
Liquid paraffin White soft paraffin Yellow soft paraffin Hard paraffin Ceresin
This group represents the most inert of chemical compounds. Lipophilic vehicles, easily spread on skin; not absorbed by skin, difficult to wash off the skin and used as occlusive effect.
2- Absorption bases
Anhydrous wool fat
Hydrophilic vehicles, usually are unhydrous bases which have the property of absorbing several times their weight of water, forming emulsion. Easily spread on skin, absorbed by skin, less occlusive and good emollient effect. However, absorption bases still possess the undesirable property of greasiness, but they are more readily removable from the skin than are oleaginous bases.
'3- Emulsion bases'
Water in oil emulsion bases Oil in water emulsion bases
Lanolin and cold cream bases are classified as water in oil emulsion base, they are used as emollients, the aqueous phase hydrating the skin and the oil phase forming an occlusive covering which prevents water loss due to evaporation. These bases are used also as vehicles for medicinal agents such as sulfur, zinc oxide , …etc. Cold cream have characteristic feature that the presence of a relatively large amount of water loosely held in the water in oil mixture , the name cold cream reffered to cooling effect produced by the slow evaporation of water when these creams were applied to the skin.
Rx, Cold Cream Borax Olive oil White bees wax Soft paraffin Distilled water
The inclusion of borax which reacted with the fatty acids present in the bees wax to form sodium soap. The soap contributed to the stability of the cream. Bees wax-Borax emulsion base is used also in preparation of Rose water cream ( Hair cream) :
Rx, Rose water Cream Borax Almond oil White bees wax Rose oil Rose water
In later years, the vegetable oils ( olive oil, almond oil) were replaced by mineral oils, because of the greater stability of mineral oil. Paraffins such as soft paraffin not used for preparation of cold cream because there are not contain fatty acids in free form so not react with alkaline substances and the result is not forming emulsifying agent. Bees wax is unhydrous base, consist of ester of higher fatty alcohol and free acids; the presence of this free acids making them acting as emulsifying agent. Wool fat (lanolin), the introduction of lanolin in 1885 , is hydrous base consist of a complex mixture of alcohol and fatty acid, so it produced water in oil emulsion; wool fat contain wool alcohol, which is the chief emulsifying agent of wool fat because wool alcohol constituent from cholesterol and lanasterol. Wool alcohol is a crude mixture of sterols and triterpene alcohol prepared by treating wool fat with alkali.
Rx, Wool alcohol Ointment Wool alcohol Hard paraffin Soft paraffin Liquid paraffin
Wool fat have the ability to absorb water, this ability attribute to the free alcohols in lanolin, mixtures of the alcohol being better emulsifiers than a single alcohol. Many lanolin derivatives (ex, lantrol) developed in order to over come some of disadvantages of lanolin such as : its stickiness, poor solubility in mineral oil, water and alcohol, its inability to penetrate in to Stratum Corneum and its rancidity.
Rx, Simple Ointment Wool fat Hard paraffin Ceto stearyl alcohol soft paraffin
Hydrophilic ointment and vanishing creams are classified as oil in water emulsion base , they are water removable and, hence, can be removed readily from skin. Vanishing cream, here we have a comparatively small amount of soap emulsifying up to 80% of water, forming O/W emulsion. The advantage of these preparation as carriers of medicinal agents supposedly lies in their high water content. This lead to more rapid release of the medicament from the base, there by favoring absorption by the skin and more rapid and satisfactory antiseptic action on the surface of the skin.
Rx, Vanishing Cream Triethanolamine Stearic acid White bees wax White soft paraffin Propylene glycol Purified water
Soap formed by the reaction between a fatty acid such as stearic acid and amine such as triethanolamine are widely used as emulsifying agents. In contrast with metallic soaps , amine soaps are less alkaline, hence, they are less likely to be irritating to injured epidermis. Emulsions prepared with amine soaps are more stable in the presence of divalent and trivalent metal ions than are those prepared with monovalent metal soaps like sodium oleate. When vanishing cream are to be used as ointment bases, One must keep in mind that they are essentially soap and, therefore are incompatible with acids or acidic substances. Therefore, their used is limited.
4- Water soluble base
Poly Ethylene glycol
Complete water soluble base have been developed from the macrogels [ poly ethylene glycols (PEG)] . They are good absorption by skin, high water solubility so very easily removed from the skin , and have good solvent properties. PEGs are a mixtures of high and low molecular weight of ethylene glycols which have the general formula : HOCH2 (CH2OCH2)n CH2OH PEGs having molecular weights from 200 to 6000 have been utilized in many formulas. Poly ethylene glycols are liquids when the molecular weight is below 700 and are wax like and increasingly solid in consistency as the molecular weight increases to 6000.
* Vegetable Oils *
Vegetable oil such as peanut oil, almond oil, sesame oil, olive oil and caster oil are mono-,di-,and tri-glycerides of mixtures of unsaturated and saturated fatty acids. These oils are used in ointments chiefly to lower the melting point or soften bases of a higher consistency and, also as an adjunct to hydrocarbon bases to increase their emollient effects and decrease their drying effects. These oils can be used as ointment bases in themselves when a high percentage of powder is incorporated in a small amount of oil so that the resulting consistency is quite viscous. Thus, zinc oxide in castor oil is prepared occasionally. Vegetable oils are used extensively in cosmetic preparations such as cold cream . the use of mineral oil in place of the vegetable oils gives a cream with enhanced spreading properties but less emolliency. Caster oil differs from the other oils in that it contains hydroxy fatty acids and, therefore, has slightly different solubility properties. Its soluble in alcohol 95%, where as the other oils are not. Trace metal contamination in oils may catalyze oxidation reaction of oils that prevented by used antioxidant , antioxidant may produce problem drug compatibility or dermal sensitivity in some patient.
* Fatty acids and alcohol *
Stearic acid is used in water removable creams as emulsifier to develop certain consistency in cream and give matt effect on skin. When a stearic soap is used as emulsifier, enough potassium hydroxide or triethanolamine usually is add to react 8% – 20% of stearic acid, the unreacted fatty acid increase consistency of cream.
Preparation of Ointment
According to the method of preparation ; ointment can be divided in to :
1- Official bases of ointment 2- Ointments prepared by trituration 3- Ointments prepared by fusion 4- Ointments prepared as emulsion
1- Official bases of Ointment
These bases prepared according to descending order of melting point, by using water bath. The most important fatty bases used in preparation ointment according to descending order of melting :
1- Bees wax Melting point : 62 – 65 Co 2- Hard paraffin Melting point : 50 – 57 Co 3- Wool alcohol Melting point : 54 Co 4- Ceto stearyl alcohol Melting point : 50 – 52 Co 5- Spermaceti Melting point : 42 – 50 Co 6- Soft paraffin ( Vaseline ) Melting point : 38 – 56 Co 7- Wool fat ( lanolin ) Melting point : 36 – 42 Co 8- Lard Melting point : 30 – 36 Co
The glycerides of unsaturated fatty acids have lower melting points than those of the saturated acids.
2- Ointment prepared by trituration
This method used when one fatty base is soft or medical agent are insoluble in fatty acid. Use alevigating agent to wet the powder and then incorporate the wetted powder in to ointment base. The process of geometric dilution will diluted the drug in to ointment. Between 2 -4 g of ointment may be lost in compounding process. The ointment is lost as it adhere to beakers, slab, and spatula. Therefore make an excess of ointment ( add 10% excess to amount).
List of insoluble medical agents
1- Lead acetate 6- Borax 2- Mercuric chloride 7- Starch 3- Salicylic acid 8- Sulphur 4- Zinc oxid 9- Calamine powder 5- Benzoic acid 10- Opium powder
3- Ointment prepared by fusion
This method used when the base is very hard and can not mixed by mortar.
List of soluble medical agent
1- Boric acid 5- Menthol 2- Chloral hydrate 6- Thaemol 3- Ephidren 7- Naphthol 4- Camphor 8- Phenol
When mix two substances with low melting point , the result is oily liquid, for this reason the method of preparation is trituration. For example, camphor with chloral hydrate or menthol with naphthol or phenol with thaemol,
4- Ointment prepared as emulsion
This method used when liquid phase mixed with oily phase with present of emulsifying agent. Example : Cold cream, and Rose water cream
Ointment mill
If preparing a large quantity of ointment, a mixing device of some type might be used instead of the ointment slab and spatula. Two options are an ointment mill, and an "electric mortar and pestle." Ointment mills produce very smooth and elegant ointments. The electric mortar and pestle allows the formulation of the ointment and the dispensing of the formulation to be done in the same container.
PACKAGING
Ointments are best packaged in tubes or in syringes if feasible. The reason for this is that there is minimal air space in the package and the product is kept clean during the administration process. Ointment jars, although widely used, expose the preparation to air and to microbial contamination when opened and when ointment is removed using the fingers. An implement similar to a tongue depressor could be used to remove the required quantity of ointment from a jar for application. Pharmacies that prepare large quantities of ointments often use plastic tubes and a tube sealer.
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