Griseofulvin micronization

Fig. 22 Dissolution fates of various griseofulvin and gri-seofulvin-succinic acid samples as determined by the oscillating bottle method. , griseofulvin, crystalline A, griseofulvin, micronized , eutectic mixture 0> physical mixture at eutectic composition , solid solution A, physical mixture at solid solution composition. The dashed line indicates the equilibrium solubility of griseofulvin in water. (From Ref. 41.).

Crison and Amidon [47,48] recently used the mass balance approach to study the variability in absorption due to intestinal transit time for water-insoluble drugs. As expected, for low dose drugs, such as digoxin, the variability in absorption sharply decreases with the increase of dissolution number via micronization. For high dose drugs, such as griseofulvin, little effect was observed when the dissolution number was increased by micronization. 

Bates TR, Carrigan PJ. Apparent absorption kinetics of micronized griseofulvin after its oral administration on single- and multiple-dose regimens to rats as a corn oil-in-water emulsion and aqueous suspension. J Pharm Sci, 1975 64 1475-1481. 

FIGURE 6.3 Micronized griseofulvin plasma profiles following oral administration (50 mg/kg) to rats in three different vehicles aqueous suspension (o), corn oil suspension (A), or com oil/water emulsion ( ). (From Carrigan, P.J. and Bates, T.R., J. Pharm. Set, 62, 1476, 1973. With permission.)... 

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. 

Reverchon E, Della Porta G, Taddeo R, Pallado P, Stassi A. Solubility and micronization of griseofulvin in supercritical CHF3. Ind Eng Chem Res 1995 34 4087-4091. 

Micronized and ultramicronized powders are used to facilitate dissolution (Fulvicin u/f and GRIS-PEG, respectively). Griseofulvin has a in plasma of -1 day. The primary metabolite is 6-methylgriseofulvin. 

Fig. 37.15 Dissolution of griseofulvin-succinic acid preparations in water at 37°C. Black symbols denote melt-products, hollow symbols plain griseofulvin or physical mixtures, respectively. Circles, solid dispersion and physical mixture, composition S (see phase diagram Fig. 37.9) triangles, eutectic solid dispersion and physical mixture, composition E squares, crystalline griseofulvin diamonds, micronized griseofulvin. Redrawn from Goldberg et...

Fig. 9.20. The relationship between absorption potential (AP) and fraction absorbed for seven representative drugs (Table 9.6). A, acyclovir B, chlorothiazide C, micronized griseofulvin D, hydrochlorothiazide E, phenytoin F, prednisolone G, digoxin (Lanoxicap). (From Dressman JB, Amidon GL, Fleisher D. Absorption potential estimating the fraction absorbed for orally administered compounds. J Pharm Sci 1985 74 588-589 with permission.)...

Bates TR, Sequeria JA. Bioavailability of micronized griseofulvin from com oil-in-water emulsion, aqueous suspension, and commercial tablet dosage forms in humans. JPharm Sci (1975) 64, 793-7. 

McGinity JW, Ku CT, Bodmeier R, Harris MR. Dissolution and uniformity properties of ordered mixes of micronized griseofulvin and a directly compressible excipient. Drug Dev Ind Pharm 1985 11(4) 891-900. 

Chiou and Riegelman reviewed the pharmaceutical applications of solid dispersion systems. These authors found complete and rapid absorption of griseofulvin dispersed in polyethylene glycol 6000 for both capsule and tablet dosage forms, in contrast to irregular and incomplete absorption from commercially available micronized drug. Munzel reviewed various formulation variables which can influence drug action. Kakemi and co-workers studied the effects of buffer components, osmotic... 

---