Crystal forms of tolbutamide from acetonitrile and 1-octanol: effect of solvent, humidity and compression pressure

• Published in: International journal of pharmaceutics Vol. 288; no. 2; pp. 335 - 348
• Main Authors: Chakravarty, P., Alexander, K.S., Riga, A.T., Chatterjee, K.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20-01-2005; Elsevier
• Subjects: 1-Octanol - chemistry; Acetonitriles - chemistry; Biological and medical sciences; Compressive Strength; Crystallization; Drug release; General pharmacology; Humidity; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polymorph; Pressure; Solvent; Solvents - chemistry; Tolbutamide; Tolbutamide - chemistry; Drug release; Polymorph; Solvent; Pressure; Tolbutamide; Humidity; Solvent effect; Drug; Compression; Crystal form; Pharmaceutical technology; Octanol; Hypoglycemic agent; Humidity effect; Sulfonylureas; Release; Polymorphism
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2004.10.006

The possibility of obtaining tolbutamide polymorphs was investigated using the solvents acetonitrile and 1-octanol. Tolbutamide is an oral hypoglycemic agent that exists in four polymorphic forms. Characterization of the various polymorphs was carried out by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), infrared spectroscopy (FTIR), optical microscopy and dissolution studies. Form A, crystallized from acetonitrile, resembled the form I polymorph, while form O, crystallized from 1-octanol, resembled the form III polymorph. Tablets of both form A and form O were produced at compression pressures of 2500
lbs and 5000
lbs using cornstarch and talc and were exposed to 40%, 75% and 95% RH conditions. DSC and PXRD studies did not show any significant drug-excipient interaction. Moreover, the change in the crystalline state of either form upon exposure to humidity was not evident. Dissolution studies showed a significantly lower drug release rate from form O tablets compressed at 5000
lbs pressure and exposed to 95% RH. Pressure and humidity had no significant effect on the dissolution profiles on the form A tablets. It was concluded that form A was the robust choice for further formulation development.