Griseofulvin drug solubility

Drugs in Class II have low aqueous solubility (but high membrane permeability), and any factor affecting dissolution rate would be expected to have an impact on the absorption of such compounds. Factors that are noted in Fig. 11, such as fluid pH, volume and viscosity, and bile secretion (especially in response to fatty foods), might be expected to play a role in dissolution rate and thereby affect absorption. Compounds that fall into this class include carbamazepine, cyclosporin, digoxin, griseofulvin, and spironolactone. Food would be expected to exert a potentially significant affect on... 

Many studies have been conducted to look at the effect of particle size on dissolution and the bioavailability of insoluble drugs [69-84], One study looked at the effect of surface area on the bioavailability of griseofulvin, which has an aqueous solubility of 0.014 mg/mL and an average dose of 500 mg. The authors showed that an approximately sixfold increase in the surface area led to a 2.5-... 

Bisrat et al. concluded that for sparingly soluble, suspended drugs, diffusional transport plays a major role in the dissolution kinetics [19]. They studied the effect of particle size and viscosity on dissolution rate and apparent diffusional distance (.h-App) of oxazepam and griseofulvin. The term apparent diffusional distance was used as a simplified measure of the distance over which diffusion dominates and was calculated as follows ... 

Griseofulvin, a BCS class II drug (Fig. 2), is a well-known example whose poor aqueous solubility causes low and erratic oral bioavailability. As shown below, griseofulvin has a hydrophobic molecular structure, and is practically insoluble in water. Its oral absorption is highly variable, ranging from 25% to 100%, depending on the crystal size. Ultramicrosize griseofulvin preparations were shown to have 100% oral absorption (12). 

Another important factor that may inLuence solubility, dissolution rate, and therefore absorption of water-insoluble compounds is the contents ofthe Gl Luids. The Gl Luids contain various materials, such as bile salts, enzymes, and mucin. Bile salts are surface active and as such could potentially enhance the rate or extent of absorption of water-insoluble drugs. Thus, the increased absorption of a water-insoluble compound, griseofulvin (GF), after a fatty meal may be facilitated by bile salt secretion into the gut resulting in solubilization [1,2],... 

Abstract Emulsions of silicone polymers having p-cyclodextrin units as lateral chains have been prepared and used for the encapsulation of the antifungal drug griseofulvin. Such technology enables the formulation of active substances that are not soluble in water as dosage fonns for topical administration. 

Particle size may play a major role in drug absorption. Dissolution rate of solid particles is proportional to surface area, and hence to particle fineness. Particle size reduction has been used to increase the absorption of a large number of poorly soluble drugs, such as bishydroxycoumarin, digoxin, griseofulvin, nitrofurantoin, and tolbutamide. 

The solid solution is a formulation in which drug is trapped as a solid solution or monomolecular dispersion in a water-soluble matrix. Although the solid solution is an attractive approach to increase drug absorption, only one drug, griseofulvin, is currently marketed in this form. 

Particle size and particle size distribution studies are important for drugs that have low water solubility. Particle size reduction by milling to a micronized form increased the absorption of low aqueous solubility drugs such as griseofulvin, nitrofurantoin, and many steroids. Smaller particle size results in an increase in the total surface area of the particles, enhances water penetration into the particles, and increases the dissolution rates. With poorly soluble drugs, a disintegrant may be added to the formulation to ensure rapid disintegration of the tablet and release of the particles. 

The bioavailability of a poorly water-soluble drug is often limited by its dissolution rate, which in turn is controlled by the surface area available for dissolution. The effect of the particle size of a drug on its dissolution rate and its biological activity is well known. For example, Atkinson et al. reported that micro-nization of griseofulvin resulted in reduction of the therapeutic dose by half. 

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