Literature DB >> 21749382

Supersaturated dissolution data and their interpretation: the TPGS-carbamazepine model case.

Georgia Charkoftaki1, Aristides Dokoumetzidis, Georgia Valsami, Panos Macheras.   

Abstract

OBJECTIVES: This study was undertaken to investigate the effect of d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) on the dissolution of carbamazepine (CBZ) commercial tablets (Tegretol(®)) as a function of temperature and to modify the reaction-limited model of dissolution for the description of classical supersaturated dissolution data.
METHODS: Solubility studies were performed using various concentrations of (i) TPGS and (ii) silicon dioxide and microcrystalline cellulose, which are excipients of Tegretol(®) at 10, 25 and 37°C. Dissolution studies were carried out using Tegretol(®) tablets, 200 mg/tab. KEY
FINDINGS: The solubility of CBZ in the presence of TPGS was found to increase in a concentration-dependent manner at all temperatures studied. Classical supersaturated dissolution curves with concentration maxima higher than the corresponding solubility values in the presence of TPGS were observed only at 10°C. The model developed was based on a time-dependent expression for the forward microconstant of the CBZ-TPGS reaction at the solid-liquid interface and it was fitted successfully to the dissolution data of CBZ in the presence of TPGS at 10°C.
CONCLUSIONS: Vitamin E TPGS increased the solubility of CBZ at all temperatures studied. The modification of the reaction-limited model of dissolution allowed us to describe classical supersaturated dissolution curves.
© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.

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Year:  2011        PMID: 21749382     DOI: 10.1111/j.2042-7158.2010.01226.x

Source DB:  PubMed          Journal:  J Pharm Pharmacol        ISSN: 0022-3573            Impact factor:   3.765


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