Pharmacy Lec 9 Notes

IV-Water - Soluble Bases

  • This group includes greaseless ointment bases with water-soluble ingredients like polyethylene glycol polymers (carbowax compounds).
  • Polyethylene glycol ointment, U.S.P. is the only pharmacopeial preparation.
  • Polyethylene glycols with molecular weights from 1,000 to 6,000 are used in ointment formulation.
  • Consistency varies from soft petrolatum-like semisolid to hard, waxy solids, increasing with molecular weight.
  • Key feature: water solubility.
  • Polyethylene glycols are innocuous and cause no more irritation than lanolin or petrolatum.
  • Increased oil in the preparation leads to increased irritation.
  • Polyethylene glycol 1500 (soft petrolatum-like semisolid) can be a vehicle for topical medicament application.
  • Higher molecular weight polyethylene glycols are blended with lower molecular weight (200-600) liquid polyethylene glycols for ointment formulation.
    • Polyethylene glycol Ointment, U.S.P. is a blend of PEG 400 and PEG 4000.
    • The base for Nitrofurozone Soluble Dressing N.F. consists of a blend of PEG 300, 1540 and 4000.
  • Polyethylene glycol Ointment, U.S.P. has desirable properties:
    • Washes off readily with water.
    • Not greasy.
    • Shows no physical changes on aging.
    • Permits ready dispersion of water-soluble medicaments.
  • Solubility limits the addition of aqueous solutions to about 5% of the total formula.
  • Adding 5% stearyl or cetyl alcohol increases the water number, allowing inclusion of 20% water.
  • Medicaments like benzoic and salicylic acids, phenol, and tannic acid have a solubilizing effect on high molecular weight PEG compounds.
  • Complexes formed have different solubility characteristics.
  • In-Vitro studies show medicaments diffuse readily from PEG bases to the skin surface, but little percutaneous absorption occurs.
  • Polyethylene glycol ointment can be a base for insoluble, water, and water-soluble medicaments.
  • Polyethylene Glycol vehicles form non-occlusive films on the skin.
  • Residual film takes up water diffused through the skin or from sweat glands, permitting water loss to the environment.
  • PEG vehicles do not maintain skin hydration, so water-soluble medicaments aren't readily transferred to the skin surface.
  • Semisolid bases that swell with water but aren't soluble are often included in water-soluble bases.
  • These bases are hydrous and usually contain an emulsifying agent.
  • Examples: preparations using Bentonite, Veegum, Gelatin, and Cellulose derivatives.
  • These bases are not greasy, spread easily, form a protective film, and are easily removed with water.
  • They don't alleviate dryness as well as petrolatum because they are non-occlusive.
  • Residual film takes up water diffused through the skin or from sweat glands, making them suitable for moist lesions.
  • Water-soluble substances should be applied to a moist base.

V-Other Members of Ointment Bases

1-Hydrogenated Oils

  • Hydrogenation addresses two disadvantages of vegetable oils for ointment bases: consistency and rancidity.
  • These are dependent on the degree of unsaturation.
  • Immiscibility with water is still a disadvantage.
  • Hydrogenation converts oils like cottonseed, soyabean, corn oil, and castor oil into white, semisolid, lard-like fats or hard, brittle waxes.
  • A completely hydrogenated oil is brittle and waxy, unsuitable for ointment base use unless mixed with a softer base.
  • If oil is hydrogenated to an ointment-like consistency, it won't be completely hydrogenated and will contain unsaturated acids or esters prone to oxidation and rancidity.
  • Hydrogenated oils are more stable than natural fats and can be used satisfactorily in prescription work.
  • To address all three issues (consistency, rancidity, miscibility):
    • Perform sulphonation after hydrogenation.
    • This yields Hydrogenated Sulfated Oils
    • Consistency is satisfactory, rancidity development is slow, miscibility with aqueous liquids is sufficient.
  • This process is mainly used with Castor oil.
  • Only sulfated hydrogenated castor oil is recommended for ointment use.
  • When hydrogenated to an iodine number less than 10, castor oil can still undergo sulfation due to the hydroxyl radical.
  • It has an ointment-like consistency, unlike other sulfated oils (liquids).
  • Consistency varies with the sulfation extent.
  • pH of 6, which is close to the skin's pH.
  • Readily incorporates water, alcohol, glycerin, glycol, and liquid petrolatum, as well as other bases like petrolatum, spermaceti, and wax.
  • Not subject to rancidity because it is completely hydrogenated and free from unsaturated acids.

2-POLYSORBATE 80, U.S.P.

  • Chemically is polyoxyethylene sorbitan mono-oleate.
  • Part of a series of compounds with partial fatty acid esterification of sorbitol anhydrides, plus a polyalkalene oxide molecule via a hydroxy group.
  • The addition of polyalkalene oxide increases water miscibility and promotes oil-in-water emulsions.
  • These compounds are known commercially as Tweens.
  • Spans are partial fatty acid esters of sorbitan without the polyalkalene oxide group.
  • Spans: Less water miscible; tend to form water-in-oil emulsions.

3-SOAPS

  • Many soaps can be used as ointment bases, most commonly sodium, ammonium, and potassium salts of oleic or stearic acid.
  • Calcium and magnesium salts are used less frequently.
  • Soaps can be preformed (e.g., sodium stearate) or prepared by mixing water with powdered soap (20-80% concentration).
  • They can also be added to other bases (e.g., soft soap in compound sulfur ointment).
  • Soaps can act as ointment bases, contribute properties, or form during preparation as a reaction product.
  • Ammonium oleate (oleic acid + ammonium hydroxide in light liquid petrolatum and wax) yields petroxolins.
  • Sodium stearate (stearic acid + sodium base in oils, water, and waxes) yields vanishing cream bases.
  • Calcium oleate (olive oil + lime water + calamine and zinc oxide) yields calamine cream (or calamine liniment in different proportions).
  • The advantage is high water content, leading to more rapid medicament release and skin absorption.

4-SILICONE DERIVATIVES

  • Examples B-lactone & Aluminum and Magnesium
  • This mainly includes mineral clay with fuller's earth and kaolin.
    • Chief representative: bentonite (in N.F. since 1940).
    • Described generally as an aluminum and magnesium silicon hydrate (H2O (Al2O3.3MgO).4SiO2. nH2O)).
  • A 2% solution has a pH of 9.5 to 9.8 (alkaline).
  • Physically: detergent, colloid, suspensoid, and emulsoid.
  • Therapeutically: safe for internal and external preparations.
  • Can be used independently as an evacuant and with insoluble substances.
  • Internally: can be used in emulsions with cod liver oil, castor oil, and liquid petrolatum.
  • Externally: can be used in lotions, creams, and pastes with or without olive oil.
  • Ointment consistency formula:
    • Bentonite: 5gm.
    • Water: 20 gm.
  • Preparation: Add water slowly to bentonite in a mortar, triturating until a smooth paste is obtained.
  • Homogeneous ointments are made by incorporating medicinal agents into the formed base.
  • Mixing insoluble powders with bentonite powder before adding water can cause graininess.
  • The base has few incompatibilities, and most medicinal agents can be added.
  • Consistency can be easily controlled by adjusting the amount of water.
  • Medicinal agent concentrations are the same as in other ointment bases.

2-Veegum

  • Colloidal magnesium aluminum silicate.
  • Inorganic emulsifier, thickener, suspending agent, and film former.
  • Disperses readily in water when added slowly with continuous agitation.
  • 1 to 4% Veegum stabilizes emulsions and suspends insoluble material.
  • Firm preparations can be made using 10% Veegum.
  • Viscosity decreases with agitation but increases again at rest (thixotropy).
  • Compatible over a wide pH range (1 to 11).
  • Compatible with large amounts of most organic solvents.

8-Silica Gel

  • Preferred base for antibiotic or antibacterial substances.
  • Silica gel with glycerin has properties suitable for certain ointments in the French Pharmacopeia (1937 report).
  • Tested as a carrier for germicidal substances: zinc oxide, boric acid, phenol, and ammoniated mercury in silica gel-glycerin base had greater zones of inhibition than U.S.P. ointments of the same substances.

Hydrogel (Silica Gel) Formulation

  • Hydrogel (Silica Gel): 45g
  • Hydrous Wool Fat: 5g
  • Liquid Petrolatum: 15 g
  • White Petrolatum Q.S. to make: 100 g
  • Preparation: Mix hydrous wool fat with liquid petrolatum in a mortar; levigate hydrogel (silica gel) with this mixture; add white petrolatum and triturate until a cream-like emulsion forms.
  • (U.S.P. = United States Pharmacopeia)

PREPARATION OF OINTMENTS

  • Ointments are applied to irritated areas.
  • Must not contain granular or gritty particles that could cause further irritation.
  • Techniques should aim to incorporate substances in the finest state of subdivision.

Properties

  • In compounding ointments, observe these rules:
    1. Insoluble substances should be in impalpable powder form.
    2. Insoluble substances are best incorporated by levigating them with a small portion of the base to form a smooth nucleus, then incorporating this into the rest of the base.
    3. Water-soluble salts should be dissolved in a small amount of water and incorporated into the base, using anhydrous lanolin if needed to absorb the aqueous solution.

Mechanical Incorporation Methods

  • Used when substances need to be reduced to a fine state of subdivision. Three methods are available:

1-Using Ointment Slab

  • Uses a heavy plate, ground on one side for a slightly roughened working surface, which helps break down gritty particles.
  • A stainless steel spatula with a long, broad, flexible, stiff blade is generally suitable.
  • If there is a risk of chemical reaction (e.g., iodine, mercury salts, salicylic acid), use a hard rubber spatula or wooden tongue depressor.
  • Technique: Rub the powder with a small amount of base until thoroughly distributed in a finely subdivided state, then incorporate this concentrated ointment into the remainder of the base.
  • Mineral oil or vegetable oil can be used as a levigating agent.
  • Using too much levigating agent may result in under softening of the finished ointment.
  • Alternatively, rub the powder with a little water, then take it up with a little wool fat (lanolin).
  • Ointments prepared by levigation must not contain granular or gritty particles, and substances must be in the finest state of subdivision.

2-Using Mortar and Pestle

  • Preferred when incorporating appreciable liquid quantities, preparing large ointment quantities, or mixing a very hard ointment (cerate) with a soft one.
  • Not as efficient as the spatula for reducing particle size because of the small surface area under levigation; particles tend to “ride” out; the grinding effect is limited.
  • The products are similar in homogeneity if the same accuracy is used.

3-Using Ointment Mill

  • Convenient and ideal for making ointments.
  • The ointment is prepared and then run through the mill until smooth and free from gritty particles.
  • Two types: