New drug–drug and drug–nutraceutical salts of anti-emetic drug domperidone: structural and physicochemical aspects of new salts

Abstract

The drug–drug multicomponent crystals (cocrystal/salt) in pharmaceutical products may boost the major challenges of fixed-dose combinations (FDCs) in coming years. The challenges associated with FDCs such as drug incompatibility, solubility differences, and stability issues can be overcome by salt/cocrystallization. Herein, the authors report eight drug–drug/drug–nutraceutical salts of the anti-emetic drug domperidone (DOM) with various drug coformers such as nicotinic acid (NCA), DL-mandelic acid (MAA), salicylic acid (SLA), orotic acid (OTA), and aspirin (ASP). The single-crystal X-ray diffraction study revealed multiple solid forms in DOM–NCA and DOM–MAA salts which differ by the presence of water. The salts, namely, DOM–MAA, DOM–OTA and DOM–ASP crystallized as anhydrous salts. The salts DOM–NCA I, DOM–SLA, and DOM–MAA I were found to be similar in crystal packing based on CrystalCMP software. The prepared salts showed lower melting temperatures as compared to DOM and coformers except for DOM–OTA. The solubility of the prepared salts in three different buffer media revealed enhancement in the solubility of DOM in pH 6.8 and 1.2 buffers. The solubility of DOM in the salts was drastically reduced in the acetate buffer (pH 4.6) as compared to the parent DOM. The dissolution study in pH 6.8 buffer demonstrated the faster drug release in the salts. The prepared salts exhibited stability under accelerated humidity conditions (40 °C, 70–75% RH) for 30 days, demonstrating the possibility of further developing these drug–drug/drug–nutraceutical salts.