title: Fast-dissolving microparticles fail to show improved oral bioavailability.
abstract: Oral dosage forms are the preferred means of delivering drugs for systemic absorption. However, development problems occur for drugs with poor water solubility and/or gastrointestinal permeability. It is generally believed that the in-vivo bioavailability of poorly water-soluble drugs from Class II of the Biopharmaceutics Classification System can be improved by increasing the dissolution rate. We have attempted to increase the in-vivo oral bioavailability of a model Class II drug (griseofulvin) by preparing rapidly-dissolving particles. The solvent-diffusion method was used to prepare particles with hydrophilic surfactants (Brij 76/Tween 80 surfactant blend) and in-vivo studies were conducted in rats. The griseofulvin particles produced were bipyramidal in habit with a particle size of 2.18 +/- 0.12 microm; they contained crystalline drug and a relatively large proportion (12% w/w) of hydrophilic surfactant. The latter and the small particle size ensured rapid particle dispersion and dissolution in-vitro. Thus, within 30 min of the in-vitro dissolution test, the bipyramidal particles had released approximately 70% of drug compared with approximately 10% from the starting material (particle size 12.61 +/- 1.11 microm). However, the rapid and increased drug dissolution in-vitro was not translated to rapid and enhanced absorption in-vivo, and the oral bioavailability of the model drug was found to be the same from the control and from the bipyramidal particles. The poor in-vivo performance of the bipyramidal particles showed that although the dissolution rate of a Class II drug is thought to be a good indicator of its in-vivo bioavailability, this is not always the case.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, London WC1N 1AX, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Wong
authors.forename: I W
authors.initials: IW
authors.lastname: Kellaway
authors.forename: S
authors.initials: S
authors.lastname: Murdan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000737:chemistry / Q000493:pharmacokinetics; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D002626:Chemistry, Pharmaceutical / Q000145:classification / Q000379:methods*; D003975:Diazepam / Q000737:chemistry / Q000493:pharmacokinetics; D005780:Gelatin / Q000737:chemistry; D006118:Griseofulvin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008297:Male; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry / Q000493:pharmacokinetics; D014867:Water / Q000737:chemistry
chemical_list: D014151:Anti-Anxiety Agents; D000935:Antifungal Agents; D002214:Capsules; D011136:Polysorbates; D013501:Surface-Active Agents; D014867:Water; D006118:Griseofulvin; D005780:Gelatin; D003975:Diazepam