CHARACTERIZATION AND INTRINSIC DISSOLUTION RATE STUDY OF MICROWAVE ASSISTED CYCLODEXTRIN INCLUSION COMPLEXES OF GEMFIBROZIL
Keywords:Gemfibrozil, Cyclodextrins, Microwave drying, Intrinsic dissolution rate
Objective: The aim of the present study was to carry out characterization and intrinsic dissolution rate study of microwave assisted inclusion complex of poorly water soluble, lipid lowering agent gemfibrozil [5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid] with naturally occurring Î²-cyclodextrins (CDs) or cycloheptaamylase.
Methods: In this work, the phase solubility study was performed to find the ratio of drug and cyclodextrin complexes. Inclusion complexes were prepared by kneading and the prepared complex was subjected to microwave drying and conventional drying techniques. The prepared complexes were evaluated by intrinsic dissolution rate studies and equilibrium solubility study. Further characterization was done by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffractometry (DSC).
Results: The phase solubility studies showed a linear AL-type diagram indicating the formation of inclusion complexes in 1:1 molar ratio Î²-CD-gemfibrozil complex with maximum stability constant of 148.88 M-1was selected for preparation of inclusion complex. The microwave dried product was identified as the inclusion complex with maximum IDR when compared to the conventional dried product.
Conclusion: This study was concluded that the microwave drying is the most suitable of the previously occurring drying techniques. Since it showed the highest solubility and IDR value.
Sachan NK, Pushkar S, Solanki SS, Bhatere DS. Enhancement of solubility of acyclovir by solid dispersion and inclusion complexation method. World Appl Sci J 2010;11:857-64.
Kurmi R, Mishra DK, Jain DK. Solid dispersion: a novel means of solubility enhancement. J Crit Rev 2016;3:1-8.
Saitoh H, Oda M, Kobayashi M, Aungst BJ. Î²-cyclodextrin as a suitable solubilizing agent for in-situ absorption study of poorly water soluble drugs. Int J Pharm 2000;280:95-102.
Al-Marzouqi AH, Shehatta I, Jobe B, Towanda A. Phase solubility, and inclusion complex of itraconazole with Î²-cyclodextrin using supercritical carbon dioxide. J Pharm Sci 2006;95:292-304.
Loftsson T, Hreinsdottir D, Masson M. Evaluation of cyclodextrin solubilization of drugs. Int J Pharm 2005;302:18-28.
Sweetman SC. Martindale: The complete drug reference. 33rd edition. London: The Pharmaceutical Press; 2002.
Drug information on line. Available from: http:// www.drugs.com. [Last accessed on 10 May 2016].
Block JH, Beale JM. Wilson and Gisvoldâ€™s textbook of organic medicinal and pharmaceutical chemistry. 11th edition. New York: Lippincott Williams and Wilkins; 2004.
Indian Pharmacopoeia. Delhi: Controller of publications; 1996.
Swati CJ, Yashwant TD, Bhanudas SK. Solubility enhancement formulation of buccal patches of ramipril cyclodextrin complex. Asian J Pharm Clin Res 2013;6:83-90.
Mohanty S, Pal A. Dissolution enhancement of seroquel by solid dispersion technique. Asian J Pharm Clin Res 2016;9:284-7.
Higuchi T, Connors KA. Phase solubility technique. Adv Anal Chem Instrum 1965;4:117-212.
Becket G, Schep LJ, Tan MY. Improvement of in vitro dissolution of praziquantel by complexation with Î±-, Î²-and Î³-cyclodextrins. Int J Pharm 1999;179:65-71.
Zingone G, Rubessa F. Preformulation study of the complex inclusion warfarin-cyclodextrin. Int J Pharm 2005;291:3-10.
Govindarajan R, Nagarsenkar MS. Influence of preparation methodology on solid-state properties of an acidic drug-cyclodextrin system. J Pharm Pharmacol 2004;56:725-33.
Viegas TX, Curatella RU, Vanuinkle LL, Brinker G. Intrinsic drug dissolution testing using the stationary disk system. Dissolution Technol 2001; 8:19-22.
Aulton ME. Pharmaceutics: the science of dosage form design. 2nd edition. New York: Churchill Livingstone; 2002.
Szejtli J. Past present and future of cyclodextrin research. Pure Appl Chem 2004;76:1825-45.
Veiga F, Fernandes C, Maincent P. Influence of the preparation method on the physicochemical properties of tolbutamide/ cyclodextrin binary system. Drug Dev Ind Pharm 2001;27:523-32.
Rattanadecho P, Makul N. Microwave assisted drying: a review of the state-of-the-art. Drying Technol 2016;34:1-38.
Arias MJ, Moyano JR, Munoz P, Gines JM, Justo A, Giordano F. Study of omeprazole-Î³-cyclodextrin complexation in the solid state. Drug Dev Ind Pharm 2000;26:253-9.
Yong CS, Choi HG, Kim DD, Jun HW, Yoo BK. Improvement of dissolution and bioavailability of nitrendipine by inclusion in hydroxypropyl Î²-cyclodextrins. Drug Dev Ind Pharm 2003;29:1085-94.
Saeed J, Mozhdeh L. Synthesis, Physical characterization and antimicrobial activity of copper (II) and cobalt (II) complex with new shifts base ligand containing thiocarbohydrazide. J Appl Sci 2015;4:135-9.
Sarvana KK, Sushma M, Prasanna RY. Dissolution enhancement of poorly soluble drugs by using complexation technique. J Pharm Sci Res 2013;5:120-4.
Yandi S, Laryssa FFR, Rochmy I. Preparation and characterization of Î²-cyclodextrin inclusion complexes oral tablets containing poorly water soluble glimipride using freeze drying method. Indonesian J Pharm 2015;26:71-7.