Crystal forms of tolbutamide from acetonitrile and 1-octanol: effect of solvent, humidity and compression pressure.
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.
Chakravarty
P
P
Department of Pharmacy Practice, University of Toledo, Toledo, OH 43606, USA.
Alexander
K S
KS
Riga
A T
AT
Chatterjee
K
K
D020003:1-Octanol / Q000737:chemistry*; D000097:Acetonitriles / Q000737:chemistry*; D019245:Compressive Strength; D003460:Crystallization; D006813:Humidity; D011312:Pressure; D012997:Solvents / Q000737:chemistry; D014044:Tolbutamide / Q000737:chemistry*
D000097:Acetonitriles; D012997:Solvents; D014044:Tolbutamide; D020003:1-Octanol; C032159:acetonitrile