Processing of carbamazepine–PEG 4000 solid dispersions with supercritical carbon dioxide: preparation, characterisation, and in vitro dissolution

• Published in: International journal of pharmaceutics Vol. 222; no. 1; pp. 129 - 138
• Main Authors: Moneghini, M., Kikic, I., Voinovich, D., Perissutti, B., Filipović-Grčić, J.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 03.07.2001; Elsevier
• Subjects: Biological and medical sciences; Carbamazepine; Crystallization; Gas antisolvent crystallisation; General pharmacology; Medical sciences; Microscopy, Electron, Scanning; PEG 4000; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Physico-chemical characterisation; Polyethylene Glycols; Solid dispersions; Supercritical fluids; Technology, Pharmaceutical; X-Ray Diffraction; Supercritical fluids; Solid dispersions; Gas antisolvent crystallisation; PEG 4000; Physico-chemical characterisation; Carbamazepine; Particle size; Pharmaceutical technology; Control release polymer; Carbon dioxide; Solid dispersion; Drug carrier; Tricyclic compound; Dissolution; Ethylene oxide polymer; Dosage form; Supercritical fluid extraction; Supercritical process; Dibenzazepine derivatives; Physicochemical properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(01)00711-6

The purpose of this study was to apply the attractive technique of the supercritical fluid to the preparation of solvent-free solid dispersions. In particular, the gas antisolvent crystallisation technique (GAS), using supercritical carbon dioxide as processing medium, has been considered to prepare an enhanced release dosage form for of the poorly soluble carbamazepine, employing PEG 4000 as a hydrophilic carrier. The physical characterisation of the systems using laser granulometer, powder X-ray diffraction, thermal analyses, and scanning electron microscopy was carried out in order to understand the influence of this technological process on the physical status of the drug. The results of the physical characterisation attested a substantial correspondence of the solid state of the drug before and after treatment with GAS technique, whereas a pronounced change in size and morphology of the drug crystals was noticed. The dramatic reduction of the dimensions and the better crystal shape, together with the presence of the hydrophilic polymer determined a remarkable enhancement of the in vitro drug dissolution rate.