MilliporeSigma

Dissolution testing of amorphous solid dispersions.

International journal of pharmaceutics (2013-02-02)
K Kogermann, A Penkina, K Predbannikova, K Jeeger, P Veski, J Rantanen, K Naelapää
ABSTRACT

The main purpose of this study was to investigate the effect of different polymers, with varying physicochemical properties and molecular weight on the stability and dissolution of co-milled amorphous solid dispersions (ASDs) of piroxicam (PRX). The stability of amorphous PRX (aPRX) in ASDs was significantly improved by the polymers. In-line Raman spectroscopy revealed that solvent mediated solid state changes occurred in biorelevant medium, however differences between ASDs were found. Thus, the dissolution behavior of ASDs of PRX and the respective polymer during conventional large volume (900ml) and a commercial small volume (20ml) dissolution testing was evaluated. The results of these studies indicated that the molecular weight of the polymer (PVP90 vs PVP25) is influencing the solubility of PRX from ASD. Interestingly the effect of molecular weight of the polymer was different than reported previously in the literature for the similar ASDs prepared by spray drying. Furthermore, the dose related bioavailability was determined by investigating the experimental saturation concentrations for different doses. These studies confirmed the findings of the dissolution studies. The differences are presumably caused by the formation of physically different diffusion layers around the ASD particles.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Polyvinylpyrrolidone, average mol wt 40,000
Sigma-Aldrich
Polyvinylpyrrolidone, suitable for plant cell culture, average mol wt 10,000
Sigma-Aldrich
Polyvinylpyrrolidone, powder, BioXtra, suitable for mouse embryo cell culture
Sigma-Aldrich
Polyvinylpyrrolidone, for molecular biology, nucleic acid hybridization tested, mol wt 360,000
Sigma-Aldrich
Polyvinylpyrrolidone, K 30
Sigma-Aldrich
Polyvinylpyrrolidone, powder, average Mw ~29,000
Sigma-Aldrich
Polyvinylpyrrolidone, powder, average Mw ~55,000
Sigma-Aldrich
Polyvinylpyrrolidone, average Mw ~1,300,000 by LS
Sigma-Aldrich
Polyvinylpyrrolidone, K 90
Sigma-Aldrich
Methocel® A15 LV, 27.5-31.5% methoxyl basis
Sigma-Aldrich
Polyvinylpyrrolidone solution, K 60, 45% in H2O
Sigma-Aldrich
Piroxicam, ≥98% (TLC)
Sigma-Aldrich
Polyvinylpyrrolidone, mol wt (number average molecular weight Mn 360)
Sigma-Aldrich
Piroxicam, meets USP testing specifications
Sigma-Aldrich
Polyvinylpyrrolidone, K 25, tested according to Ph. Eur.
Sigma-Aldrich
Polyvinylpyrrolidone, average mol wt 10,000
Piroxicam for system suitability
Piroxicam, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Methocel® A15C, medium viscosity, Methoxyl content 27.5-31.5 %
Sigma-Aldrich
Methyl cellulose, tested according to Ph. Eur.
Sigma-Aldrich
Methyl cellulose, viscosity: 400 cP
Sigma-Aldrich
Methyl cellulose, viscosity: 4,000 cP
Sigma-Aldrich
Methyl cellulose, viscosity: 1,500 cP
Sigma-Aldrich
Povidone, meets USP testing specifications
Sigma-Aldrich
Methyl cellulose, meets USP testing specifications, viscosity: 1,500 cP
Sigma-Aldrich
Methyl cellulose, viscosity: 15 cP
Sigma-Aldrich
Methyl cellulose, viscosity: 25 cP
Sigma-Aldrich
Methyl cellulose, meets USP testing specifications, viscosity: 400 cP
Sigma-Aldrich
Methyl cellulose, viscosity: 15 cP, BioReagent, suitable for cell culture
Sigma-Aldrich
Kollidon® 25