Creams - Pharmaceutical Information PDF

CREAMS Creams are white, semisolid preparations, often medicated, intended for external application to the skin and mucous membranes. Creams are dosage forms formulated to provide preparations that are essentially miscible with the skin secretion. They are intended to be applied to the skin or cert...

CREAMS Creams are white, semisolid preparations, often medicated, intended for external application to the skin and mucous membranes. Creams are dosage forms formulated to provide preparations that are essentially miscible with the skin secretion. They are intended to be applied to the skin or certain mucous membranes for protective, therapeutic or prophylactic purposes especially where an occlusive effect is not necessary. Pharmaceutical and cosmetic creams are generally o/ w emulsions (aqueous creams), although the term is also used occasionally to describe semisolid w/ o emulsions (oily creams). Advantages of creams 1. Convenient and easy to apply 2. Avoids first pass metabolism 3. Low risk 4. There is achievement of efficacy with lower total daily dose due to continuous drug imput Difference between creams and ointments **1. Appearance** Generally, creams are white to off-white color but may have different colors such as yellow, While ointments are usually translucent but may have various colors like light yellow, yellow or black. **3. Nature of Formulation ** Generally, the cream is a water-based semisolid preparation whereas an Ointment is an oil-based semisolid preparation. **4. Constituents** Cream contains more than 20% water and volatiles and normally less than 50% hydrocarbons, waxes, or [polyols](https://en.wikipedia.org/wiki/Polyol) as the vehicle. On the other hand, ointment contains less than 20% water and volatiles, and more than 50% hydrocarbons, waxes, or polyols as the vehicle **5. Viscosity** Generally, Creams are thin. While ointments are thick. **6. Spreadability** Pharmaceutical cream may be easily spreadable on the skin and are better to use when a large surface area of the body needs to apply medication. On the other hand, Pharmaceutical ointments may be less spreadable on the skin than cream and make an occlusive layer on the skin. Also, the spreading of ointments on moist skin surfaces may be tough due to the hydrophobic nature of most ointments. **7. Greasiness ** Generally, Creams are non-greasy or less greasy than ointment. While ointments are greasy than cream. **8. Absorption ** Creams are absorbed faster via the skin than ointments. While ointments are absorbed slower through the skin than creams. **9. Onset of action ** The onset of action of cream is faster than the ointment. While the onset of action of ointment is slower than cream. **10. Duration of action** Cream stays for a lesser time thus the duration of action is short. On the other hand, an ointment stays longer on the skin, so the duration of action is longer than cream. **11. Stains on clothing ** There is no chance of staining cloth by using creams. Whereas Ointments can leave stains on clothing. **13. Wash off** Creams are non-greasy thus more easily washed off using water whereas ointments are not easily washed off. Types of creams A cream may be 'water-in-oil' (hydrophobic) or 'oil-in-water' (hydrophilic) depending on the emulsifying agent used. A cream is always miscible with its continuous phase. \* Water-in-oil creams (oily creams) as bases -- These are produced by the emulsifying agents of natural origin (e.g. beeswax, wool alcohols or wool fat). These bases have good emollient properties. They are creamy, white or translucent and rather stiff. Water-in-oil creams tend to be greasy, and although this conveys a greater feeling of richness, they do not mix well with aqueous wound exudates and are also sometimes difficult to wash off the skin. They do however hydrate the skin by occlusion, an important actor in drug permeation. \* Oil-in-water creams (aqueous creams) as bases -- These are produced by the synthetic waxes (e.g. macrogol and cetomacrogol). They are the best bases to use for rapid absorption and penetration of drugs. They are thin, white and smooth in consistency. o/ w creams readily mix with tissue exudates and are more easily removed by washing. Properties of ideal Cream bases The ideal base should possess the following properties 1. it should liquefy at room temperature 2. it should penetrate the epidermis through natural openings at a desired release rate 3. it should be non toxic 4. it should be non irritant 5. it should be non inflammatory 6. it should be inert 7. it should not retard wound healing 8. it should possess pharmaceutical elegance 9. it should possess long term stability on storage 10. it should be compatible with most medicaments and the skin **GENERAL COMPOUNDING PROCEDURES FOR COMPOUNDING OF CREAMS** The following are common terms that are used within the extemporaneous preparation of creams. Trituration This is the term applied to the incorporation, into the base, of finely divided insoluble powders or liquids. The powders are placed on the tile and the base is incorporated using the 'doubling-up' technique. Liquids are usually incorporated by placing a small amount of base on a tile and making a 'well' in the centre. Small quantities of liquid are then added and mixed in. Take care not to form air pockets that contain liquid, which if squeezed when using an inappropriate mixing action will spray fluid on the compounder and surrounding area. Trituration can be successfully achieved using a mortar but this method is usually reserved for large quantities. Levigation This is the term applied to the incorporation into the base of insoluble coarse powders. It is often termed 'wet grinding'. It is the process where the powder is rubbed down with either the molten base or semi-solid base. A considerable shearing force is applied to avoid a gritty product. **THE PREPARATION OF A CREAM FROM FIRST PRINCIPLES** 1\. As with other types of emulsion, hygiene is extremely important and all surfaces, spatulas and other equipment must be thoroughly cleaned with industrial denatured alcohol (IDA). IDA is better than freshly boiled and cooled purified water as it will quickly evaporate, leaving no residue. 2\. Always make an excess as it is never possible to transfer the entire cream into the final container. 3\. Determine which of the ingredients are soluble in/miscible with the aqueous phase and which with the oily phase. Dissolve the water-soluble ingredients in the aqueous phase. 4\. Melt the fatty bases in an evaporating dish over a water bath at the lowest possible temperature. Start with the base with the highest melting point. These should then be cooled to 60°C (overheating can denature the emulsifying agent and the stability of the product can be lost). 5\. Substances that are soluble/miscible with the oily phase should then be stirred into the melt. 6\. The temperature of the aqueous phase should then be adjusted to 60°C. 7\. The disperse phase should then be added to the continuous phase at the same temperature. Hence, for an oil-in-water product, add oil to water. For a water-in-oil product, add water to oil. 8\. Stir the resulting emulsion vigorously without incorporating air, until the product sets. Do not hasten cooling as this produces a poor product. **THE INCORPORATION OF INGREDIENTS INTO A CREAM BASE** In addition to the preparation of a cream from first principles, it is common to incorporate either liquid or solid ingredients into a cream base. THE INCORPORATION OF SOLIDS INTO A CREAM BASE If the cream base has been prepared from first principles, the solid can be incorporated into the cream as it cools. Alternatively, if using a pre-prepared base, soluble and insoluble solids may be incorporated using the method employed for insoluble solids. Soluble solids should be added to the molten cream at the lowest possible temperature and the mixture stirred until cold. Insoluble solids should be incorporated using a glass tile and spatula. If there is more than one powder to be added, these should be triturated together in a mortar using the 'doubling-up' technique prior to transfer to a glass tile. Coarse powders. A minimum quantity of cream should be placed in the centre of the glass tile and used to levigate the powders. A considerable lateral shearing force should be applied to avoid a gritty product. The powder/fatty base mixture may then either be returned to the evaporating basin with the remaining cream and stirred until cold or the remaining cream in the evaporating basin may be allowed to cool and triturated with the powder/cream mixture on the tile. Fine powders may be triturated into the otherwise finished cream on a glass tile. Small amounts of powder should be added to an equal amount of cream, i.e. using the 'doubling-up' technique. These should be well triturated. THE INCORPORATION OF LIQUIDS INTO A CREAM BASE Non-volatile, miscible liquids may be mixed with the molten cream in the evaporating basin. Alternatively, if a pre-prepared base is used, then incorporate as for volatile or immiscible liquids. Volatile or immiscible liquids, e.g. coal tar solutions, should be triturated with the cream on the glass tile. A very small amount of the cream should be placed on the glass tile and a 'well' made in the centre. Traditionally, small quantities of liquid should be gently folded in to avoid splashing. An alternative method is to spread a small amount of the cream on the tile and then score it with a spatula. Then add small quantities of the liquid and fold into the base gently. If using coal tar or other volatile ingredients, these should not be weighed until immediately before use and the beaker in which it has been weighed should be covered with a watch glass to prevent evaporation. In addition, always remember that volatile ingredients should not be added to molten base. PACKAGING CONTAINERS AND CLOSURES As all pharmaceutical creams are intended for external use, a suitable container would be either an amber wide-necked ointment jar or a metal collapsible tube. Advantages of metal collapsible tubes include: - Its narrow orifice prevents contamination of the unused parts - Wastage is reduced since the patient is unlikely to remove an excessive portion. - The tubes collapse after the product is expelled, preventing the addition of air and reducing the risk of hydrolysis or oxidative damage. Pharmaceutical ointment jars come in a variety of different sizes and it is important to choose a suitably sized container to match the volume of preparation to be dispensed. Amber glass jars are preferable to clear glass jars as they protect the preparation from degradation by light. More recently, plastic ointment jars have become available and, although cheaper than glass jars, are less preferable because of an increased likelihood of the products reacting with the container (e.g. as can occur with preparations containing coal tar). When packaging a cream into an ointment jar, ensure that the cream is packed well and that no air pockets are visible. This will produce a product with a professional appearance. Discard dates Some official texts may give a suggested discard date for certain extemporaneously prepared creams. In the absence of any guide, it is suggested that creams are given a four-week discard date. This is significantly shorter than the suggested discard date for extemporaneously prepared ointments (which is three months) because of the susceptibility of creams to microbial contamination Diluted creams would normally be given a two-week discard date. Remember that as patients frequently misunderstand the term 'expiry' it is suggested that a preferred method of indicating shelf-life on the label of extemporaneously compounded products is to apply the term 'Discard after' or 'Do not use after' followed by a definite date and/or time. Labelling In addition to the standard requirements for the labelling of extemporaneous preparations, the following points need to be taken into consideration: \* 'For external use only' -- This warning must be added to the label of all extemporaneously prepared creams as all creams are for external use only.