Dual strategy to enhance domperidone dissolution: mechanochemically synthesized multicomponent salts in...

The pharmaceutical ingredient domperidone (DOM) acts as a prokinetic and antiemetic agent, commonly indicated for the treatment of gastroparesis, epigastric pain, reflux, and nausea. Its clinical efficacy, however, is limited by poor water solubility and intestinal metabolism, resulting in low bioavailability. To address these challenges, this study combines two strategies: generating more soluble multicomponent solid forms of DOM and incorporating them into orodispersible tablets (ODTs). This dual approach combines the rapid buccal disintegration of ODTs with the enhanced dissolution of multicomponent forms, thereby improving absorption. Two solid forms were produced via water-assisted mechanochemical synthesis: anhydrous DOM DL-mandelate and monohydrated DOM saccharinate. Both solids were fully characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR). Subsequently, ODTs were developed using these multicomponent forms, with their performance assessed through dissolution assays via a validated HPLC (high-performance liquid chromatography) technique. The ODT containing monohydrated DOM saccharinate showed markedly improved dissolution compared with tablets containing DOM alone or DOM DL-mandelate. Combined with the rapid disintegration of ODTs, this approach may accelerate DOM absorption through the oral mucosa or gastrointestinal tract, offering faster and more effective therapeutic outcomes.