No 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.

Aims: Metformin is a high-solubility and low-permeability drug that is widely used as an oral antidiabetic medication. In many countries, metformin is available as multiple generic formulations, with over 10 registered products, which are approved to be dispensed interchangeable. The aims of this study were to assess the in vitro dissolution profiles of a range of commercial brands of metformin hydrochloride tablets under a range of in vitro conditions and to determine whether differences in in vitro dissolution can be detected under a range of conditions. Methodology: Single and multiple (2 or 4) tablets from all brands were tested in both pH 6.8 and 0.1M HCl (gastric pH) dissolution medium and collected samples were analysed by highperformance liquid chromatography. Results: At least three distinct dissolution profiles were seen, designated slow, medium and fast