IngentaConnect Dissolution Rates and Supersaturation Behavior of Amorphous Repag...

Authors: Sinswat, Prapasri; Matteucci, Michal E.; Johnston, Keith P.; Williams, Robert O.

Source: Journal of Biomedical Nanotechnology, Volume 3, Number 1, April 2007 , pp. 18-27(10)

Publisher: American Scientific Publishers

Abstract:

Rapidly dissolving nanostructured particles containing amorphous repaglinide (REP) were produced by controlled precipitation. Rapid in vitro dissolution rates and high levels of supersaturation (drug concentration/crystalline equilibrium solubility) were achieved using different stabilizing polymers including Hypromellose, polyvinylpyrrolidone, polyvinyl alcohol, and polyethylene glycol. The dissolution and supersaturation characteristics of amorphous REP depended on the surface area of the particles and the miscibility of REP with the polymer employed to prevent drug crystallization in the solid phase. Each of the polymers contained hydrogen bonding groups to favor miscibility with the drug. Of the various formulations investigated, REP/Hypromellose had the highest surface area leading to the highest dissolution rate in aqueous media under sink conditions. For each of the polymers, except for PVA, the level of supersaturation was on the order of 5 and decayed only slightly for up to 24 h. In addition, the amorphous REP/Hypromellose system produced high supersaturation after 3 months storage at 25 °C/60% RH indicating it was stable against crystallization. This understanding of the effect of polymer stabilizers on drug morphology and subsequently, dissolution rates and supersaturation, may be used to facilitate rational design of dosage forms with the potential for improved bioavailability.

Keywords: CONTROLLED PRECIPITATION; REPAGLINIDE; DISSOLUTION; SUPERSATURATION; POLYMERS

Document Type: Research article

DOI: 10.1166/jbn.2007.001

Dissolution Rates and Supersaturation Behavior of Amorphous Repaglinide Particles Produced by Controlled Precipitation