Prakash Thapa, Ritu Thapa, Uttam Budhathoki, Panna Thapa^*

Show more
Department of Pharmacy, School of Science, Kath-mandu University, Dhulikhel, Nepal.
Department of Pharmaceutical Sciences, School of Health and Allied Sciences, Pokhara University, Lekhnath, Nepal.
Show less

Abstract: Domperidone Maleate (DOM), an antiemetic drug, has been used in treatment of adults and children. It has low aqueous solubility and hence low bioavailability. In present study, an attempt has been made to enhance the solubility of DOM by inclusion complexation with Hydroxypropyl-β-Cyclodextrin (HP-β-CD) using kneading technique and formulation of fast disintegrating tablets by using Sodium Starch Glycolate as superdisintegrant. Solubility analysis of DOM in different concentrations of HP-β-CD was carried out. Design of experiment (DOE) is done by using MINITAB 15.1 software to find out the variable for dissolution and disintegration time. HP-β-CD and SSG were identified as the variable for disintegration time and dissolution. For optimization of the concentration of HP-β-CD and SSG, two factors at two levels design through central composite design (CCD) were used which gave 13 formulations. All formulations are evaluated for characteristics such as weight variation, hardness, friability, disintegration time and dissolution of drug. Solubility of DOM increases linearly with increase in concentration of HP-β-CD. The optimum concentration of HP-β-CD is found to be in 1:2 molar ratios and SSG of 7%. The In-Vitro dissolution studies of optimized formulation and market sample were carried out in USP type II apparatus at different time intervals of 5, 10, 15 and 30 minutes at 50 rpm in 0.1 N HCl. The dissolution and disintegration time of optimized formulation is found better than market sample.

Keywords: Domperidone Maleate; Hydroxypropyl-β-Cyclodextrin; Inclusion Complexes

Cite this paper: Thapa, P. , Thapa, R. , Budhathoki, U. and Thapa, P. (2014) Solubility Enhancement of Domperidone Fast Disintegrating Tablet Using Hydroxypropyl-β-Cyclodextrin by Inclusion Complexation Technique. Pharmacology & Pharmacy, 5, 238-249. doi: 10.4236/pp.2014.53031.

References

[1]   Ansel, H.C., Popovich, N.G. and Allen, L.V. (2005) Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. 8th Edition, Lippincott Williams & Willkins.

[2]   Zade, P.S., Kabitkwar, P.S. and Sakarkar, D.M. (2009) Formulation, Evaluation and Optimization of Fast Dissolving Tablet Containing Tizanidine Hydrochloride. International Journal of Pharm Tech Research, 1, 34-42.

[3]   Sharma, D. (2013) Formulation Development and Evaluation of Fast Disintegrating Tablets of Salbutamol Sulphate for Respiratory Disorders. ISRN Pharmaceutics, 2013, 1-13. http://dx.doi.org/10.1155/2013/674507

[4]   Chandrasekhar, R., Hassan, Z., Alhusban, F., Smith, A.M. and Mohammed, A.R. (2009) The Role of Formulation Excipients in The Development of Lyophilized Fast-Disintegrating Tablets. European Journal of Pharmaceutics and Biopharmaceutics, 72, 119-129. http://dx.doi.org/10.1016/j.ejpb.2008.11.011

[5]   Amin, A.F. (2006) Emerging Trends in the Development of Orally Disintegrating Tablet Technology.

[6]   Okuda, Y., Irisawa, Y., Okimoto, K., Osawa, T. and Yamashita, S. (2009) A New Formulation for Orally Disintegrating Tablets Using a Suspension Spray-Coating Method. International Journal of Pharmaceutics, 382, 80-87.
http://dx.doi.org/10.1016/j.ijpharm.2009.08.010

[7]   Bhowmik, D., Chiranjib, B., Krishnakant, P. and Chandira, R.M. (2009) Fast Dissolving Tablet: An Overview. Journal of Chemical and Pharmaceutical Research, 1, 163-177.

[8]   Salustio, P.J., Feio, G., Figuirinhas, J.L., Pinto, J.F. and Cabral Marques, H.M. (2008) The Influence of the Preparation Methods on the Inclusion of Model Drugs in β-Cyclodextrin Cavity. European Journal of Pharmaceutics and Biopharmaceutics, 71, 377-386. http://dx.doi.org/10.1016/j.ejpb.2008.09.027

[9]   Sachan, R., Khatri, K. and Kasture, S.B. (2010) Self-Emulsifying Drug Delivery System a Novel Approach for Enhancement of Bioavalibility. International Journal of PharmTech Research, 2, 1738-1745.

[10]   Savjani, K.T., Gajjar, A.K. and Savjani, J.K. (2012) Drug Solubility: Importance and Enhancement Techniques. ISRN Pharmaceutics, 2012, 195727.

[11]   Ishiguro, T., Morishita, E., Iohara, D., Hirayama, F., Wada, K., Motoyama, K., Arima, H. and Uekama, K. (2011) Some Pharmaceutical and Inclusion Properties of 2-Hydroxybutyl-&Beta-cyclodextrin Derivative. International Journal of Pharmaceutics, 419, 161-169. http://dx.doi.org/10.1016/j.ijpharm.2011.07.044

[12]   Osborne, R.J., Slevin, M.L., Hunter, R.W. and Hamer, J. (1985) Cardiotoxicity of Intravenous Domperidone. Lancet, 386, 385. http://dx.doi.org/10.1016/S0140-6736(85)92515-2

[13]   Challa, R., Ahuja, A., Ali, J. and Khar, R.K. (2005) Cyclodextrins in Drug Delivery: An Updated Review. AAPS PharmSciTech, 6, 329-357. http://dx.doi.org/10.1208/pt060243

[14]   Goel, H., Vora, N. and Rana, V. (2008) A Novel Approach to Optimize and Formulate Fast Disintegrating Tablets for Nausea and Vomiting. American Association of Pharmaceutical Scientists, 9, 774-781.

[15]   Shimpi, S., Chauhan, B. and Shimi, P. (2005) Cyclodextrins: Application in Different Routes of Drug Administration. Acta Pharmaceutica, 55, 139-156.

[16]   (1996) ASEAN Guidelines for Validation of Analytical Procedures. ICH Q2B.

[17]   Nalluri, B.N., Chowdary, K.P., Murthy, K.V., Hayman, A.R. and Becket, G. (2003) Physicochemical Characterization and Dissolution Properties of Nimesulide-Cyclodextrin Binary Systems. AAPS PharmSciTech, 4, 6-17.
http://dx.doi.org/10.1208/pt040102

[18]   (2007) British Pharmacopoeia, II.

[19]   Costa, P. and Lobo, J.M.S. (2001) Modeling and Comparison of Dissolution Profiles. European Journal of Pharmaceutical Sciences, 13, 123-133. http://dx.doi.org/10.1016/S0928-0987(01)00095-1