FORMULATION AND INVESTIGATION OF POLYMERIC MULTIPLE UNIT PELLET SYSTEMS CONSISTING OF SUSTAINED RELEASE GLIMEPIRIDE AND IMMEDIATE RELEASE ATORVASTATIN CALCIUM
Objective: The objective of the present work was to develop novel fixed-dose combinations (FDCs) for improvement of glucose tolerance in type II diabetes mellitus patients associated with dyslipidemia.
Methods: Multiple unit pellet systems (MUPSs) consisting of sustained release (SR) glimepiride and immediate release atorvastatin calcium pellets were formulated. The SR glimepiride pellets were prepared using a combination of locust bean gum and gum ghatti/guar gum. Similarly, the immediate release of atorvastatin calcium pellets was prepared using locust bean gum suspension as a binder.
Results: The formulated pellets were characterized using Fourier transform infrared spectroscopy (FTIR) and Differential scanning calorimetry (DSC). Further, surface morphology of the formulated pellets was done by scanning electron microscopy (SEM). FT-IR and DSC studies suggested that there were no chemical interactions between the drug and natural polymers. SEM studies revealed that formulated pellets were in spherical shape. Based on in vitro evaluation, the SR glimepiride formulation developed using a combination of 2% locust bean gum and 2.5% gum ghatti polymers sustained the release of the drug up to 12 h. Similarly, the immediate release atorvastatin calcium formulation containing 1% w/w locust bean gum suspension as a binder and 7% croscarmellose sodium showed fast disintegration of pellets. The in vivo studies in albino Wistar rat revealed that there was an improvement in bioavailability of the drugs. Stability studies showed that there were no significant changes in the drug content and physical appearance of the prepared SR glimepiride and immediate release atorvastatin pellet formulations.
Conclusion: Thus, the formulated FDC as MUPS can be used as an alternative approach for treating diabetes mellitus-induced dyslipidemia.
2. Zhang X, Cui X, Li F, Wang S, Liu X, Hui L, et al. Association between diabetes mellitus with metabolic syndrome and diabetic microangiopathy. Exp Ther Med 2014;8:1867-73.
3. Bhad ME, Abdul S, Jaiswal SB, Chandewar AV, Jain JM, Sakarkar DM. MUPS tablets a brief review. Int J Pharm Tech Res 2010;2:847-55.
4. Altuntas TG, Erk N. Liquid chromatographic determination of atorvastatin in bulk drug, tablets, and human plasma. J Liq Chromatogr Relat Technol 2004;27:83-93.
5. Inukai K, Watanabe M, Nakashima Y, Sawa T, Takata N, Tanaka M, et al. Efficacy of glimepiride in Japanese Type 2 diabetic subjects. Diabetes Res Clin Pract 2005;68:250-7.
6. Ho JE, Paultre F, Mosca L. Is diabetes mellitus a cardiovascular disease risk equivalent for fatal stroke in women? Data from the women’s pooling project. Stroke 2003;34:2812-6.
7. Patel SA, Patel NG, Joshi AB. Multiple unit pellet system (MUPS) based fast disintegrating delayed-release tablets for pantoprazole delivery. Int J Pharm Pharm Sci 2018;10:77-84.
8. Higuchi TK. A phase solubility technique. Adv Anal Chem Instrum 1965;4:117-211.
9. Clarke GM, Newton JM, Short MB. Comparative gastrointestinal transit of pellet systems of varying density. Int J Pharm 1995;114:1.
10. Rojas J, Correa D. Comparative evaluation of the release properties of verapamil hcl and carbamazepine from microcrystalline cellulose II pellets. Int J Pharm Pharm Sci 2017;9:182-6.
11. Kilor VA, Sapkal NP, Awari JG, Shewale BD. Development and characterization of enteric-coated immediate-release pellets of aceclofenac by extrusion/spheronization technique using ?-carrageenan as a pelletizing agent. AAPS PharmSciTech 2010;11:336-43.
12. Bechard SR, Leroux JC. Coated pelletized dosage form: Effect of compaction on drug release. Drug Dev Ind Pharm 1992;18:1927-44.
13. Dash SK, Khan AS, Das SR, Padhan A, Rout D, Behera BC. Formulation and in-vitro evaluation of sustained released glibenclamide microspheres. Int J Pharm Sci Res 2012;3:1433.
14. Reddy GL. Development and in vitro-in vivo evaluation of extended-release multiple-unit pellet system tablets of metoprolol succinate. Asian J Pharm 2016;10:S39-42.
15. Arunkumar N, Deecaraman M, Rani C, Mohanraj KP, Venkateskumar K. Formulation development and in vitro evaluation of nanosuspensions loaded with atorvastatin calcium. Asian J Pharm 2014;23;4:28-33.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.