Background: Domperidone (DOM), a dopamine receptor antagonist, is used as antiemetic for the treatment of gastroparesis, vomiting, and nausea. The low water solubility of DOM leads to a low dissolution rate and variable bioavailability. The aim of this study was to enhance the solubility of DOM by the preparation of micron-sized particles. Materials and Methods: The in situ micronization process was carried out using solvent change method in the presence of Soluplus® or PEG6000as stabilizing agents. DOM was dissolved in appropriate solvent (acetone and methanol 1:1 v/v), and the stabilizing agent was dissolved in water (as nonsolvent). The nonsolvent was poured rapidly into the drug solution under stirring by a homogenizer, and the resultant was freeze dried. The crystalline shape and particle size of DOM and interaction of DOM with stabilizers were investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC), and then, dissolution test was carried out. Results: Optimum formulation was composed of DOM (0.5%) and PEG6000 (0.1%) with the lowest particle size (3 μm) and the highest DE60%(95.95%) as compared to pure DOM (particle size of 13.4 μm and DE60%52.18%). Conclusion: SEM micrographs showed uniform and spherical shape of microcrystals. FTIR, XRD, and DSC studies indicated the micron size of the microcrystals and no interference between the drug and the stabilizer.
Bittner B, Mountfield RJ. Intravenous administration of poorly soluble new drug entities in early drug discovery: The potential impact of formulation on pharmacokinetic parameters. Curr Opin Drug Discov Devel 2002;5:59-71.
Rinaki E, Valsami G, Macheras P. Quantitative biopharmaceutics classification system: The central role of dose/solubility ratio. Pharm Res 2003;20:1917-25.
Vandana KR, Prasanna Raju Y, Harini Chowdary V, Sushma M, Vijay Kumar N. An overview on in situ micronization technique – An emerging novel concept in advanced drug delivery. Saudi Pharm J 2014;22:283-9.
Reddymasu SC, Soykan I, McCallum RW. Domperidone: Review of pharmacology and clinical applications in gastroenterology. Am J Gastroenterol 2007;102:2036-45.
Siepmann J, Faisant N, Akiki J, Richard J, Benoit JP. Effect of the size of biodegradable microparticles on drug release: Experiment and theory. J Control Release 2004;96:123-34.
Javadzadeh Y, Jafari-Navimipour B, Nokhodchi A. Liquisolid technique for dissolution rate enhancement of a high dose water-insoluble drug (carbamazepine). Int J Pharm 2007;341:26-34.