Evaluation of compatibility of domperidone with selected excipients used in preparation of orally disintegrating tablets.

Abstract

Objective: This study aims systematic evaluation of potential drug excipient interactions and by using a multi technique analytical approach.

Significance: This study will help in finding out compatibility among domperidone and different excipients, and will facilitate excipients selection for development a stable formulation of ODTs.

Methods: Binary mixtures of domperidone and excipients which are commonly used in preparation of solid dosage forms were prepared (1:1 w/w), with and without added moisture. Studied excipients included microcrystalline cellulose, Tablettose-80 (spray-dried lactose), croscarmellose sodium, magnesium stearate, and aspartame. Samples were subjected to higher temperature and relative humidity (45 °C and 75% RH) for 90 days, as per ICH guidelines. Samples were analyzed at regular interval for drug content (by high-performance liquid chromatography), chemical interaction (by Fourier transform infrared [FTIR] spectroscopy), solid state characterization (by differential scanning calorimetry and powder X-ray diffraction [XRD]), and moisture uptake (by Karl Fischer titration).

Results: Drug content of all the samples remained within the range of 95%-105% throughout the study. FTIR spectra showed absence of chemical interactions as all the functional groups remained unchanged. Characteristic melting endotherm was observed in DSC thermograms. XRD analysis showed same crystallinity and polymorphic transitions were not observed. Depending upon their physicochemical properties, excipient showed different levels of hygroscopicity. Highest water sorption was observed with croscarmellose sodium and lactose whereas magnesium stearate remained non hygroscopic. Moisture uptake study showed that chemical or solid-state stability of domperidone was not affected by exposure to high relative humidity.

Conclusions: Domperidone exhibited robust chemical and physical stability across all excipient environments tested. While excipient hygroscopicity varied significantly, no incompatibilities were detected that would limit formulation development of ODTs.