Formulation development of methylprednisolone dispersible tablets using quality by design approach
The objective of this study was to enhance the solubility of Methylprednisolone by choosing micronized form of drug and to enhance patient compliance by formulating it as dispersible tablets using quality by design (QbD) approach. Dispersible tablets of Methylprednisolone were developed by 23 factorial design. In this study independent variables were concentrations of MCC 102, CCS and Magnesium stearate and dependent variables were disintegration time, hardness and dissolution. The resulting data was fitted into Design Expert Software (Trial Version) and analyzed statistically using analysis of variance (ANOVA). The response surface plots were generated to determine the influence of concentration of MCC 102, CCS and magnesium stearate on responses. The tablets were prepared by direct compression method by choosing micronized form of drug and formulations were evaluated for the standard of dispersible tablets. Results showed that no significant drug-polymer interactions in FTIR studies. According to QbD suggestion the formulation O1 (Desirability- 0.73) with MCC-38mg, CCS-3.5mg and magnesium stearate-2.5mg was formulated and evaluated. The disintegration time was found to be 69 seconds, hardness was found to be 64N and in vitro dissolution with in 30minutes. Optimized O1 formulation was within the limits of standards of dispersible tablets with increased water solubility and better patient compliance. Stability study on optimized O1 formulation showed that there is no significant changes during study period. Thus, O1 formulation was found to be stable. The study indicates that formulation of Methylprednisolone dispersible tablets by using QbD approach is a promising formulation development method.
Keywords: Dispersible tablets, Methylprednisolone, Direct compression, Quality by Design and ANOVA.
2. Raghunathan. Rapid dissolving, uniform drug compositions and their preparation. United States Patent. May 14, 1985; Patent no: 4,517,179.
3. Bi YX, Sunada H, Yonezawa Y, Danjo K. Evaluation of rapidly disintegrating tablets by direct compression method. Drug Devlop Ind Pharm 1999; 25:571-81.
4. Kuchekar BS, Badhan AC, Mahajan HS. Mouth dissolving tablet: A novel drug delivery system. Pharm Times 2003; 35:7-14.
5. Reddy LH, Ghosh BR. Fast dissolving drug delivery systems: A review of the literature. Indian J Pharm Sci 2002; 64:331-6.
6. Pilgaonkar PS, Rustomjee MT, Gandhi AS, Bagde, Barve V. Novel Dispersible Tablet Composition. United States Patent;Dec 12, 2008. Patent no: 20080312168.
7. DeGrazio F, Vedrine L. Quality by Design for Primary Container Components. Quality by Design for Biopharmaceutical Drug Product Development: Springer; 2015; 365-401.
8. Charoo NA, Shamsher AA, Zidan AS, Rahman Z. Quality by design approach for formulation development: a case study of dispersible tablets. Int J Pharm 2012; 423(2):167-78.
9. Fahmy R, Kona R, Dandu R, Xie W, Claycamp G, Hoag SW. Quality by design I: application of failure mode effect analysis (FMEA) and Plackett–Burman design of experiments in the identification of “main factors” in the formulation and process design space for roller-compacted ciprofloxacin hydrochloride immediate-release tablets. AAPS PharmSciTech. 2012; 13(4):1243-54.
10. Chang R-K, Raw A, Lionberger R, Yu L. Generic development of topical dermatologic products: formulation development, process development, and testing of topical dermatologic products. AAPS PharmSciTech. 2013; 15(1):4152.
11. Park S-J, Choo G-H, Hwang S-J, Kim M-S. Quality by design: screening of critical variables and formulation optimization of Eudragit E nanoparticles containing dutasteride. Archives of pharmacal research. 2013; 36(5):593-601.
12. Banker GS, Anderson NR. Tablets. In: Lachman L, Libermann HA, Kanig JL, editors. The Theory and Practice of Industrial Pharmacy. 3rd ed. New Delhi: Varghese Publishing House; 1987:293-9.
13. Jadhav SB, Kaudewar DR, Kaminwar GS, Jadhav AB, Kshirsagar RV, Sakarkar DM. Formulation and Evaluation of Dispersible tablets of Diltiazem Hydrochloride. Int J Pharm Tech Res. 2011; 3(3):131-21.
14. Bi YX, Sunada H, Yonezawa Y, Danjo K. Evaluation of rapidly disintegrating tablets by direct compression method. Drug Dev Ind Pharm 1999; 25:571-81.
15. Bhagwati ST, Hiremath SN, Sreenivas SA. Comparative evaluation of disintegrants by formulating cefixime dispersible tablets. Indian J Pharm Edu Res 2005; 39:194-7.
16. Indian Pharmacopoeia. New Delhi: Controller of Publications; 1996:735.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).