COMPARISON AND CHARACTERIZATION OF INCLUSION COMPLEXES AND SOLID DISPERSIONS IN ENHANCEMENT OF DISSOLUTION RATE OF POORLY WATER SOLUBLE DRUG
Objective: The purpose of the present study was to enhance solubility and dissolution characteristics of indomethacin by preparing inclusion complexes with hydroxypropyl Î²-cyclodextrin (HP Î²-CD) and solid dispersions with PEG 6000 to enhance its in vitro drug release and to further formulate it as a tablet
Methods: Solid dispersions (SDs) and inclusion complexes (ICs) of Indomethacin with PEG 6000 and HP Î²-CD respectively were prepared to enhance the dissolution rate of this poorly water-soluble drug belonging to BCS class II. A comparison was made between two systems: solid dispersions with PEG 6000 obtained using melting and solvent evaporation technique, inclusion complexes with HP Î²-CD prepared by kneading technique. SDs were prepared in 1:1, 1:2, 1:3 and ICs in 1:0.25, 1:0.5, 1:1 w/w ratios of drug: polymer. Both the systems were characterized by FTIR, SEM, DSC, X-RD.
Results: The dissolution of indomethacin increased with the increase in the concentration of the polymers. F4 and F9 formulations showed complete drug release in less than 30 min. Dissolution studies indicated that cyclodextrin complexes showed a better enhancement of dissolution rate when compared to solid dispersions. CDs were found to be more effective than PEGs at lower concentrations. These formulations were further compressed as tablets.
Conclusion: The FTIR and DSC studies showed that no interactions existed between the drug and the polymer.
2. Markus V, Klaus K, Jennifer BD. Dissolution improvement of four poorly water-soluble drugs by co-grinding with commonly used excipients. Eur J Pharm Biopharm 2008;68:330-7.
3. Mahamoud ELB, Gihan F, Mohamoud F. Improvement of solubility and dissolution rate of indomethacin by solid dispersions in gelucire 50/13 and PEG 4000. Saudi Pharm J 2009;7:217-25.
4. Raymond CR, Paul JS, Marian EQ. Handbook of pharmaceutical excipients 6th edition; 2016. p. 210-214, 517-521.
5. Punitha S, Vedha HBN, Karthikeyan D. Enhancement of celecoxib solubility by solid dispersion using mannitol. Int J Pharm Pharm Sci 2010;2:109-11.
6. Ladan AN, Gurinder S, Gaurav S, Kimia FK. Solid dispersion: methods and polymers to increase the solubility of the poorly soluble drug. J Appl Pharm Sci 2012;2:170-5.
7. Buchi NN, Chowdary KPR, Murthy KVR, Hayman AR, Becket G. Physicochemical characterization and dissolution properties of nimesulide-cyclodextrin binary systems. AAPS PharmSciTech 2003;4:1-12.
8. Rajesh A, Pinkesh P, Sangeeta A, Chirag PJ, Jaiman P. Solubility enhancement of rifampicin by using liquisolid technique. Int J Pharm Res Bio-Sci 2013;2:203-18.
9. Polli JE, Rekhi GS, Augsburger LL, Shah VP. Methods to compare dissolution profiles and a rationale for wide dissolution specification for Metaprolol tartrate tablets. J Pharm Sci 1997;8:690â€“700.
10. Arun PK, Narayanan N, Rajalakshmi G. Preparation and evaluation of solid dispersion of terbinafine hydrochloride. Int J Pharm Sci Rev Res 2010;3:130-4.
11. Rajesh K, Prasanna RY, Nagaraju R. Dissolution enhancement of valsartan using natural polymers by solid dispersion technique. Der Pharm Lett 2013;5:126-34.
12. Sucheta B, Dyandevi M, Mithun VK, Rajendra DP. Solubility enhancement of the antihypertensive agent by solid dispersion technique. Int J Pharm Life Sci 2011;2:970-5.
13. Sanjay JK, Anand U, Jasmine M, Vidula S. A modified solvent method for preparation of solid dispersion. Iranian J Pharm Sci 2011;8:287-98.
14. Parve B, Balaji T, Avinash B. Studied on solid dispersions: an overview on Solubility enhancement of poorly water-soluble drugs. Int J Pharma Bio Sci 2014;5:7-25.
15. Enhancement of dissolution rate and physicochemical characterization of irbesartan inclusion complexes using cyclodextrins. Res J Pharm Tech 2017;10:301-6.
16. Tukaram K, Wadher SJ, Anitha K, Sominath D. Improvement of aqueous solubility and In vitro drug release rate of telmisartan using hydrophilic base by various dispersion techniques. Int J Pharm Tech Res 2016;9:28-34.