Using thermal analysis as quality control for famotidine polymorph contamination.

Abstract

It is well known that undesirable polymorphs in active pharmaceutical ingredients, in any proportion, can cause harm, both fnancially and to the health of patients. Famotidine (FTD) exhibits three known polymorphs, A, B, and C, which difer in their physicochemical properties. Form B is pharmaceutically preferred because it shows better biopharmaceutical properties.

This study used thermal analysis as the main tool in the quality control of polymorphs in FTD batches. The impact on solubil- ity, polymorphic stability, and dissolution profle of tablets was also studied. One batch (called F01), of fve characterized,

showed contamination with polymorph A. F01 was ~2.6 times less soluble than the pure form B batch (called F05) in pH 4.5 phosphate bufer, the recommended US Pharmacopoeia dissolution medium for FTD tablets. Moreover, it was observed that after storage for 3 months (40±2 °C and RH of 75±5%), F05 also showed contamination with form A, representing a risk that should be monitored during the quality control of FTD raw materials and drug formulations. Nevertheless, tablets manufactured with these batches did not show diferences in their dissolution profles, indicating that the amount of form A found in F01 was not sufcient to alter release of the drug from the formulated tablet. Therefore, thermal analysis is efcient in detecting polymorphic contaminations of FTD raw materials, suggesting adequate and fast methods for quality control of drug products and thus, avoiding compromised therapeutic efcacy.