Dissolution rate of griseofulvin

Table 3 The Effect of Hydrophilic Excipients on the Dissolution Rates of Griseofulvin (a Biophannaceutical Classification System Class II Drug)...

C. Flego, M. Lovrecich and E Rubessa, Dissolution rate of griseofulvin from solid dispersions with poly(vinylmethylether/maleic anhydride) . Drug Dev. Ind. Pharm., vol. 14, no. 9, pp. 1185-1202, 1988. 

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. 

This effect of particle size on dissolution rate of sparingly soluble drug substances has been demonstrated in many instances by the superior dissolution rates observed after size reduction. Examples of compounds studied in such work include methylprednisolone (Higuchi et al., 1963), l-isopropyl-7-methyl-4-phenylquinazolin-2(lH)-one (Kornblum and Hirschorn, 1970), griseofulvin (Ullah and Cadawader, 1971), monophenylbutazone (Habib and Attia, 1985), nitrofurantoin (Eyjolfsson, 1999), and piroxicam (Swanepoel et al., 2000). 

Katchen B, Symchowicz S (1967). Correlation of dissolution rate and griseofulvin absorption in man. 

Smirnova 1, Tuerk M, Wischumerski R, Wahl M A (2005) Comparison of different methods for enhancing the dissolution rate of poorly soluble drugs Case of griseofulvin. Eng. Life Sd 5(3) 277-280... 

A result of this analysis is shown in Fig. 7.6 for the cetomacrogol-griseofulvin system [29]. The considerable effect of stirring rate on the dissolution rate of the powdered drug is seen, leading to the conclusion that it is necessary to choose... 

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... 

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 ... 

An increased rate of dissolution resulting from particle size reduction has also been observed for several excipients. For example, griseofulvin systems containing ethylcellulose of size fraction 710-850 /im released the drug almost 25% faster than the same systems containing ethylcellulose of size fraction 1000-2000 fim. The authors interpret these results in terms of more excipient particles being available to interact with the drug in the fraction of lower size [69],... 

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],... 

Sanghavi, N.M. Munot, D.S. Kamath, P.R. Shaikh, F.AR. Solvent deposition of griseofulvin on excipients and its effects on dissolution rate. Indian Drugs 1988,26, 23-27. 

Amorphous materials typically have a higher rate of dissolution and a higher kinetic solubility that their crystalline counterparts (Fig. 1). These characteristics can be exploited to enhance the rate and extent of absorption of poorly water-soluble APIs from the gastrointestinal tract. Such formulation approaches have been described for many APIs including indomethacin, griseofulvin, and several barbiturates. ... 

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. 

The range of substances over which there is pharmacopoeial control of particle size is shown in Table 1.7 sometimes the aim is to achieve uniformity in a product rather than any direct benefit. The control exercised over the particle size of cortisone acetate and griseofulvin is due to their very low solubility the experience is that if the solubility of a dmg substance is about 0.3% or less then the dissolution rate in vivo may be the rate-controlling step in absorption. 

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