Gels: Pharmaceutical Topical Formulations PDF

GELS Pharmaceutical gels are often simple phase, transparent semi-solid systems that are being increasingly used as pharmaceutical topical formulations. The liquid phase of the gel may be retained within a three-dimensional polymer matrix. Drugs can be suspended in the matrix or dissolved in the li...

GELS Pharmaceutical gels are often simple phase, transparent semi-solid systems that are being increasingly used as pharmaceutical topical formulations. The liquid phase of the gel may be retained within a three-dimensional polymer matrix. Drugs can be suspended in the matrix or dissolved in the liquid phase. Advantages of gels 1\. Stable over long periods of time 2\. Good appearance 3\. Suitable vehicles for applying medicaments to skin and mucous membranes giving high rates of release of the medicament and rapid absorption. Gels are usually translucent or transparent and have a number of uses: - Anaesthetic gels - Coal tar gels for use in treatment of psoriasis or eczema - Lubricant gels - Spermicidal gels. GELLING AGENTS The consistency of gels can vary widely depending on the gelling agent used in their preparation. Common gelling agents used in aqueous gels are discussed below. Generally the medication in a gel is released quite freely provided the medicament does not bind with the polymer or clay used in its formation. Tragacanth \* Concentrations of 2--5% of tragacanth are used to produce different viscosities. \* Tragacanth is a natural product and is therefore liable to microbial contamination. \* The gum tends to form lumps when added to water and therefore most formulae will include a wetting agent such as ethanol, glycerol or propylene glycol. By pre-wetting the tragacanth, the problems of a lumpy product should be minimised, and should lumps develop they will disperse easily on standing. Alginates \* The viscosity of alginate gels is more standardized than that of tragacanth. \* Alginate concentrations of 1.5% produce fluid gels. \* Alginate concentrations of 5--10% produce dermatological grade gels suitable for topical application. \* Wetting agents (such as glycerol) need to be employed to prevent production of a lumpy product. Pectin \* Pectin is suitable for acid products. \* It is prone to microbial contamination. \* It is prone to water loss and therefore necessitates the addition of a humectant (e.g. glycerol, propylene glycol or sorbitol) Gelatin Gelatin is rarely used as the sole gelling agent in dermatological preparations. It is usually combined with other ingredients such as pectin or carmellose sodium. Cellulose derivatives \* Cellulose derivatives are widely used and form neutral, stable gels. \* They exhibit good resistance to microbial attack. \* They form clear gels with good film strength when dried on the skin. \* Methylcellulose 450 is used in strengths of 3--5% to produce gels. \* Carmellose sodium (sodium carboxymethylcellulose) is used in concentrations of 1.5--5% to make lubricating gels. In higher concentrations it is used to make dermatological gels. Carbomer \* Carbomer is useful in production of clear gels (provided too much air is not incorporated in the gel production) \* In concentrations of 0.3--1%, carbomer acts as a lubricant. \* Carbomer is used in dermatological preparations in concentrations of 0.5--5%. Polyvinyl alcohol \* Polyvinyl alcohol is useful for preparing quickdrying gels. \* It leaves a residual film that is strong and plastic. \* It provides gels that have good skin contact and therefore ensures the medicament has good skin contact. \* Differing viscosities are achieved depending on the concentration of polyvinyl alcohol used (normally 10--20%) and the grade of polyvinyl alcohol employed. Clays \* Bentonite is used in concentrations of 7--20% to formulate dermatological bases. \* The resultant gel is opalescent, therefore less attractive to the patient. \* On drying, the gel leaves a powdery residue on the skin. OTHER ADDITIVES FOR GELS Other additives for gels include humectants and preservatives Humectants Loss of water from a gel results in a skin forming. The addition of a humectant can minimise this. Examples of additives that may be added to help retain water include: \* glycerol in concentrations of up to 30% \* propylene glycol in concentrations of approximately 15% \* sorbitol in concentrations of 3--15%. Preservatives Gels have higher water content than either ointments or pastes and this makes them susceptible to microbial contamination. Choice of preservative is determined by the gelling agent employed GENERAL METHOD OF MANUFACTURE FOR GELS 1 Heat all components of the gel (with the exception of water) to approximately 90 C. 2\. Heat water to approximately 90 C. 3\. Add water to oil, stirring continuously. Avoid vigorous stirring as this will introduce bubbles. **PASTES** - Introductions - Uses of pastes - Bases used in pastes - Method of preparation of pastes - Official examples of pastes and method of preparation - Containers and labeling Pastes Pastes are semi-solid preparations for external use. They consist of finely powdered medicaments combined with White Soft Paraffin BP or Liquid Paraffin BP or with a non-greasy base made from glycerol, mucilages or soaps. Pastes contain a high proportion of powdered ingredients (25-50%) and therefore are normally very stiff. Because pastes are stiff they do not spread easily and therefore this localizes drug delivery. This is particularly important if the ingredient to be applied to the skin is corrosive, such as dithranol, coal tar or salicylic acid. It is easier to apply a paste to a discrete skin area such as a particular lesion or plaque, and thereby not compromising the integrity of healthy skin. Pastes are also useful for absorbing harmful chemicals, such as the ammonia that is released by bacterial action on urine, and so are often used in nappy products. Also because of their high powder content, they are often used to absorb wound exudates. Because pastes are so thick, they can form an unbroken layer over the skin which is opaque and can act as a sun filter. The principal use of pastes was traditionally as an antiseptic, protective or soothing dressing. Often before application the paste was applied to lint and then applied as a dressing. Difference between pastes and ointments 1. Pastes are very thick and stiff while ointment are soft semisolids 2. Pastes are less greasy while ointments are more greasy 3. Pastes are applied with a spatula or spread on lint, while ointment are applied directly on skin 4. Pastes form a localized protective coating, while ointments are used as emollients or occlusions for the skin. 5. Pastes are less macerating while ointments are more macerating. PHARMACEUTICAL USE OF PASTE 1. They are used primarily as antiseptic, protective or soothing dressings 2. They are used as sun blocks and wind blocks 3. They can be used to treat infections due to their high osmotic pressure 4. Used to absorb serous secretions due to the stiffness of the preparation 5. They are used to ensure local action of drugs METHOD OF PREPARING PASTES Pastes can be prepared in the same manner as ointments, through incorporation method of fusion method. However, when a levigating agent is to be used to render the powdered component smooth, a portion of the base is often used, rather than a solvent, which would soften the paste. Incorporation method: This method is ideal for drug that insoluble in hydrocarbon base or for bulky powders. - Levigation is commonly used in small scale preparation of pastes to reduce particle size and grittiness of the added powders. - A mortar and pestle or an ointment tile can be used. - Powders are sifted using a sieve before incorporation. - A paste is formed by combining the powder and a small amount of melted or softened lipophilic base. - The paste is then triturated, reducing the particle size. - The levigated paste is then added to the remaining semisolid hydrophobic base and the mixture made uniform and smooth by rubbing them together with a spatula on the ointment tile. Fusion method: This is ideal for drug that are soluble in hydrocarbon base, or for drugs that are dissolved in water prior to being added to a molten absorption base. The disadvantage is that this method does not give an elegant finished product unless high shear mixing can be used, and also, it does not remove powder lumps in the mixture. - All solid powders must be sifted and triturated - Melt the soft bases eg paraffin in an evaporating basin over a water bath - Stir some powder into the melted base - As the base cools, add other ingredients in decreasing order of melting points, stirring continuously to ensure a homogeneous mix before leaving to set.