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: