Polymorphic properties of micronized carbamazepine produced by RESS

• Published in: International journal of pharmaceutics Vol. 252; no. 1; pp. 225 - 233
• Main Authors: Gosselin, P.M, Thibert, R, Preda, M, McMullen, J.N
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 18.02.2003; Elsevier
• Subjects: Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Calorimetry, Differential Scanning - methods; Carbamazepine; Carbamazepine - analysis; Carbamazepine - chemistry; Carbon dioxide; Crystallization; Medical sciences; Micronization; Microscopy, Electron, Scanning; Neuropharmacology; Particle Size; Pharmacology. Drug treatments; Polymorphism; Stereoisomerism; Supercritical; Technology, Pharmaceutical - instrumentation; Technology, Pharmaceutical - methods; Micronization; Supercritical; Carbamazepine; Carbon dioxide; Polymorphism; Particle size; Drug carrier; Anticonvulsant; Liquid carbon dioxide; Crystallinity; Tricyclic compound; Supercritical solvent; Microparticle; Dibenzazepine derivatives
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(02)00649-X

Carbamazepine microparticles were produced by the rapid expansion of supercritical carbon dioxide solutions (RESS) method. The characteristics of the resulting particles were studied by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and image analysis. X-ray diffractograms and SEM photomicrographs revealed that the crystalline nature of the produced carbamazepine microparticles depended on operating pressure and temperature conditions. Different polymorphs were obtained under various operating conditions. Under certain temperature (below 40 °C) and pressure (below 240 bar) conditions, it was possible to form primarily the carbamazepine polymorph stipulated by US Pharmacopeia. A significant reduction was observed in the particle size and size distribution range of carbamazepine produced by RESS. The processed particles had a mean diameter smaller than 3 μm and a size distribution range between 0.5 and 2.5 μm compared to unprocessed starting material with a mean diameter of approximately 85 μm and a size distribution range between 15 and 336 μm. Thus, this study demonstrates that the polymorphic characteristics of carbamazepine microparticles produced by the RESS method can be controlled by varying operating pressure and temperature parameters.