IN VITRO RELEASE KINETICS OF SIMVASTATIN FROM METHYL CELLULOSE GEL
Objective: a) To estimate the ideal percentage of polymer (methyl cellulose) and the drug (simvastatin) for controlled release gel. b) To evaluate the release kinetics and physical property.
Methods: Drug polymer interaction was studied using Differential Scanning Calorimeter (DCS) and Fourier TransformÂ InfraredÂ Spectroscopy (FTIR). Simvastatin powder was hydrolysed to active simvastatin hydroxyl acid. Nine gel formulations using three different concentrations of simvastatin (SMV) (1.2%, 1.7% and 2.2%) and three concentration of methyl cellulose (MC) (4%, 5% and 6%) were prepared. Drug release kinetics of 9 formulations was assessed using open end tube method with the dialysis membrane. The physical property was studied using rheometer.
Results: DSC and FITR results showed no drug polymer interaction. The release kinetics of all nine formulations was in a controlled manner. 4% MC 2.2% SMV, 5% MC 2.2% SMV, 6% MC 2.2% SMV showed controlled drug release compared to other six formulations. The pH of all the nine formulations ranged between 6.21â€“6.25. The drug content of each formulation was above 97.9%.
Conclusion: This study showed that increase in polymer concentration in the gel increased the controlled release of the drug and addition of the drug to the gel decreased the viscosity of the gel.
2. Rosling BG, Slots J, Christersson LA, GrÃ¶ndahl HG, Genco RJ. Topical antimicrobial therapy and diagnosis of subgingival bacteria in the management of inflammatory periodontal disease. J Clin Periodontol 1986;13:975-81.
3. Funosas E, Feser G, Escovich L, Maestri L. Alteration of hemostasis in patients treated with subgingival NSAIDs during periodontal therapy. Acta Odontol Latinoam 2012;25:103-8.
4. Hopper SM, McCarthy M, Tancharoen C, Lee KJ, Davidson A, Babl FE. Topical lidocaine to improve oral intake in children with painful infectious mouth ulcers: a blinded, randomized, placebo-controlled trial. Ann Emerg Med 2014;63:292-9.
5. Goodson JM, Holborow D, Dunn RL, Hogan P, Dunham S. Monolithic tetracycline-containing fibers for controlled delivery to periodontal pockets. J Periodontol 1983;54:575-9.
6. Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature 1990;343:425-30.
7. Bellosta S, Ferri N, Bernini F, Paoletti R, Corsini A. Non-lipid-related effects of statins. Ann Med 2000;32:164-76.
8. Pradeep AR, Thorat MS. Clinical effect of subgingivally delivered simvastatin in the treatment of patients with chronic periodontitis: a randomized clinical trial. J Periodontol 2010;81:214-22.
9. Morlock M, Kissel T, Li YX, Koll H, Winter G. Erythropoietin loaded microspheres prepared from biodegradable LPLG-PEO-LPLG triblock copolymers: protein stabilization and in-vitro release properties. J Controlled Release 1998;56:105-15.
10. Rajabi-Siahboomi AR, Jordan MP. Slow release HPMC matrix systems. Eur Pharm Rev 2000;5:21â€“3.
11. Sarunyoo Songkro, Naranut Rajatasereekul, Nipapat Cheewasrirungrueng. In vitro studies of muco adhesiveness and release of nicotinamide oral gels prepared from bioadhesive polymers. World Acad Sci Eng Technol 2009;55:113-20.
12. Levina M, Rajabi-Siahboomi AR. The influence of excipients on drug release from hydroxypropyl methylcellulose matrices. J Pharm Sci 2004;93:2746-54.
13. Thylin MR, McConnell JC, Schmid MJ, Reckling RR, Ojha J, Bhattacharyya I, et al. Effects of simvastatin gels on murine calvarial bone. J Periodontol 2002;73:1141-8.
14. Ju Hyeong Jeon, Mark V, Thomas, David A, Puleo. Bioerodible devices for intermittent release of simvastatin acid. Int J Pharm 2007;340:6-12.
15. Balaji S, Sunitha A. Development and validation of spectrophotometeric method for simultaneous determination of simvastatin and ezetimibe in tablet formulations. Pak J Pharm Sci 2010;23:375-8.
16. ICH Harmonized Tripartite Guidelines. Stability Testing of New Drug Substances and Products. ICH Committee; 2003. p. 8.