Solubility Enhancement of Domperidone by Solvent Change In situ Micronization Technique

Enteshari, Saeede; Varshosaz, Jaleh

Solubility Enhancement of Domperidone by Solvent Change In situ Micronization Technique

Document Type : Original Article

Authors

Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

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 PEG_{6000 (}0.1%) with the lowest particle size (3 μm) and the highest DE_60%(95.95%) as compared to pure DOM (particle size of 13.4 μm and DE_60%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.

Keywords

References

1.	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. [PUBMED]
2.	Rinaki E, Valsami G, Macheras P. Quantitative biopharmaceutics classification system: The central role of dose/solubility ratio. Pharm Res 2003;20:1917-25. [PUBMED]
3.	Chaudhary A, Nagaich U, Gulati N, Sharma VK, Khosa RL, Partapur MU. Enhancement of solubilization and bioavailability of poorly soluble drugs by physical and chemical modifications: A recent review. J Adv Pharm Educ Res. 2012;2(1):32-67.
4.	Elouzi AA, El-Buzidi NO. A review On Solubility Enhancement Techniques of Poor Water-Soluble Drugs for Oral Pharmaceutical Formulation. Annals of advanced sciences. 2017;9;1(3).
5.	Rasenack N, Müller BW. Dissolution rate enhancement by in situ micronization of poorly water-soluble drugs. Pharm Res 2002;19:1894-900.
6.	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. [PUBMED]
7.	Varshosaz J, Talari R, Mostafavi S, Nokhodchi A. Dissolution enhancement of gliclazide using in situ micronization by solvent change method. Powder Technol. 2008;187(3):222-30.
8.	Varshosaz J, Khajavinia A, Ghasemlu M, Ataei E, Golshiri K, Khayam I. Enhancement in dissolution rate of piroxicam by two micronization techniques. Dissolut Technol. 2013;20(3):15-23.
9.	Nighute A, Bhise S. Enhancement of dissolution rate of rifabutin by preparation of microcrystals using solvent change method. Drugs 2009;2:3.
10.	Pouretedal HR. Preparation and characterization of azithromycin nanodrug using solvent/antisolvent method. Int Nano Lett 2014;4:103.
11.	Steckel H, Rasenack N, Müller BW. In situ micronization of disodium cromoglycate for pulmonary delivery. Eur J Pharm Biopharm 2003;55:173-80.
12.	Papdiwal A, Pande V, Sagar K. Design and characterization of zaltoprofen nanosuspension by precipitation method. Pharm Chem 2014;6:s161.
13.	Reddymasu SC, Soykan I, McCallum RW. Domperidone: Review of pharmacology and clinical applications in gastroenterology. Am J Gastroenterol 2007;102:2036-45. [PUBMED]
14.	Tyagi R, Dhillon V. Enhancement of solubility and dissoultion rate of domperidone using cogrinding and kneading technique. J Drug Deliv Ther 2012;2:4.
15.	Patel K, Prasad K, Bajpai M. Enhancement of dissolution rate of domperidone using melt granulation technique. Pharm Lett 2011;3:25-33.
16.	Islam A, Haider SS, Reza MS. Formulation and evaluation of orodispersible tablet of domperidone. Dhaka Univers J Pharm Sci. 2012;10(2):117-22.
17.	Kotikalapudi LS, Adepu L, VijayaRatna J, Diwan PV. Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles. Int J Pharm Biomed Res 2012;3:22-9.
18.	Sharma S, Suresh PK. Formulation,in vitro characterization and stability studies of self microemulsifying drug delivery systems of domperidone. Int J Innov Pharm Res 2010;1:66-73.
19.	Ghodke DS, Nakhat PD, Yeole PG, Naikwade NS, Magdum CS, Shah RR. Preparationa and Characterization of domperidone Inclusion complexes with cyclodextrin: Influence of preparation method. Iran J Pharm Res. 2010:145-51.
20.	Van den Mooter G, Augustijns P, Blaton N, Kinget R. Physico-chemical characterization of solid dispersions of temazepam with polyethylene glycol 6000 and PVP K30. Int J Pharm 1998;164:67-80.
21.	Zhang CH, Zhao BX, Huang Y, Wang Y, Ke XU, Zhao BJ, et al. A novel domperidone hydrogel: Preparation, characterization, pharmacokinetic, and pharmacodynamic properties. J Drug Deliv 2011;2011 Article ID 841054,9.
22.	Jayaramudu T, Raghavendra GM, Varaprasad K, Subba Reddy GV, Reddy AB, Sudhakar K, Sadiku ER. Preparation and characterization of poly (ethylene glycol) stabilized nano silver particles by a mechanochemical assisted ball mill process. J Appl Polym Sci 2016;133:7. DOI: 10.1002/APP.43027.
23.	Rasenack N, Hartenhauer H, Müller BW. Microcrystals for dissolution rate enhancement of poorly water-soluble drugs. Int J Pharm 2003;254:137-45.
24.	Djuris J, Nikolakakis I, Ibric S, Djuric Z, Kachrimanis K. Preparation of carbamazepine–Soluplus® solid dispersions by hot-melt extrusion, and prediction of drug–polymer miscibility by thermodynamic model fitting. Eur J Pharm Biopharm. 2013;84(1):228-37.
25.	Paaver U, Tamm I, Laidmäe I, Lust A, Kirsimäe K, Veski P, et al. Soluplus graft copolymer: potential novel carrier polymer in electrospinning of nanofibrous drug delivery systems for wound therapy. BioMed Res Int. 2014;2014.
26.	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. [PUBMED]
27.	Varshosaz J, Emami J, Hashemi S. Influence of different solid-dispersion techniques upon the release of dimenhydrinate from chewing-gum formulations. Sci Pharm 2002;70:391-406.
28.	Mohamed AI, Elsayed Abd-Motagaly AM, Ahmed OA, Amin S, Mohamed Ali AI. Investigation of drug – Polymer compatibility using chemometric-assisted UV-spectrophotometry. Pharmaceutics 2017;9:7.
29.	Dinte E, Bodoki E, Leucuta S, Adela Iuga C. Compatibility studies between drugs and excipients in the preformulation phase of buccal mucoadhesive systems. Farmacia 2013;61:703-12.
30.	Yu H, Zhao X, Zu Y, Zhang X, Zu B, Zhang XPreparation and characterization of micronized artemisinin via a rapid expansion of supercritical solutions (RESS) method. Int J Mol Sci 2012;13:5060-73.
31.	Ghodke D, Chaulang GM, Patil KS, Nakhat PD, Yeole PG, Naikwade NS, Magdum CS. Solid state characterization of domperidone: Hydroxypropyl-β-cyclodextrin inclusion complex. Indian J Pharm Sci 2010;72:245. [PUBMED] [Full text]
32.	Mandal B, Alexander K, Riga A. Evaluation of the drug-polymer interaction in calcium alginate beads containing diflunisal. Pharmazie 2010;65:106-9.
33.	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. [PUBMED]
34.	Kim S, Kwon JH, Lee JJ, Kim CW. Microcrystallization of indomethacin using a pH-shift method. Int J Pharm 2003;263:141.

Advanced Biomedical Research