FACTORIAL STUDIES ON ENHANCEMENT OF DISSOLUTION RATE AND FORMULATION OF ACECLOFENAC TABLETS EMPLOYING Î’CDAND KOLLIPHOR HS15
Aceclofenac is an effective anti inflammatory and analgesic drug. It belongs to class II under Biopharmaceutical classification system and exhibit low and variable oral bioavailability due to its poor solubility. It is practically insoluble in water and aqueous fluids and its oral absorption is dissolution rate limited. It needs enhancement in solubility and dissolution rate for improvement of its oral bioavailability and therapeutic efficacy. The objective of the present study is to enhance the dissolution rate and formulation development of aceclofenac tablets with fast dissolution characteristics employing Î²CD and Kolliphor HS15, a non ionic surfactant. The individual and combined effects of Î²CD (factor A) and Kolliphor HS15 (factor B) on the dissolution rate of aceclofenac from solid inclusion complexes and their tablets were evaluated in a series of 22 factorial experiments. The feasibility of formulating aceclofenac - Î²CD-Kolliphor HS15 inclusion complexes into tablets with fast dissolution rate characteristics was also investigated. Kolliphor HS15 has not been investigated earlier for this purpose.
The individual and combined effects of Î²CD and Kolliphor HS15 in enhancing the dissolution rate and dissolution efficiency of aceclofenac from solid inclusion complexes and their tablets were highly significant (P < 0.01). The dissolution of aceclofenac was rapid and higher in the case of aceclofenac- Î²CD and aceclofenac- Î²CD - Kolliphor HS15 complexes prepared when compared to aceclofenac pure drug. Î² CD alone gave a 8.66 fold increase and in combination with Kolliphor HS15 it gave 9.85 fold increase in the dissolution rate of (K1) of aceclofenac. Aceclofenac â€“Î²CD â€“ Kolliphor HS15 inclusion complexes could be formulated into compressed tablets by wet granulation method and the resulting tablets also gave rapid and higher dissolution of aceclofenac. Aceclofenac tablets formulated with Î²CD and Kolliphor HS15 individually gave 4.75 and 6.1 fold increase in the dissolution rate and those containing drug - Î²CD -Kolliphor HS15 complex gave much higher enhancement (21.35 fold) in the dissolution rate when compared to tablets formulated with aceclofenac pure drug. Combination of Î²CD and Kolliphor HS15 gave much higher enhancement in the dissolution rate of aceclofenac tablets than is possible with them individually. A combination of Î²CD with Kolliphor HS15 is recommended to enhance the dissolution rate in the formulation development of aceclofenac tablets with fast dissolution rate characteristics.Keywords: Aceclofenac, Î² Cyclodextrin, Kolliphor HS15, Dissolution Rate, Aceclofenac Tablets, Formulation development.
2. Fromming KH, Szejtli J. Cyclodextrins in Pharmacy. Kluwer Academic Publications, Dordrecghi; 1994. p. 20.
3. Duchene D, Woussidjewe D, Dumitriu S. Polysaccharides in Medical Applications. Marcel Dekker: New York; 1996. p. 575-602.
4. Thompson DO. Cyclodextrins-enabling excipients: their present and future use in pharmaceuticals. Crit Rev Therapeutic Drug Carrier System 1997;14(1):1-104.
5. Hedges AR. Industrial applications of cyclodextrins. Chem Rev 1998;98:2035-44.
6. Rajebahadur M, Zia H, Nues A, Lee C. Mechanistic study of solubility enhancement of nifedipine using vitamin E TPGS or solutol HS-15. Drug Delivery 2008;13(3):201-6.
7. Alani, AW, Rao DA, Seidel R, Wang J, Jiao J, Kwon GS. The effect of novel surfactants and Solutol HS 15 on paclitaxel aqueous solubility and permeability across a Caco-2 monolayer. J Pharm Sci 2010;99(8):3473-85.
8. Han HK, Lee BJ, Lee HK. Enhanced dissolution and bioavailability of biochanin A via the preparation of solid dispersion: in vitro and in vivo evaluation. Int J Pharm 2011;30(1-2):89-94.
9. Sherry KU, Ranga Velageti. Pharmaceutical Technology; 2010. p. 108-10.
10. Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol 1975;27:48-9.