Development and optimization of floating alginate microspheres of repaglinide using Box-Behnken experimental design
DOI:
https://doi.org/10.37285/ijpsn.2023.16.1.3Abstract
Background: Due to short-lasting action, fast clearance and enzymatic instability of anti-diabetic drugs result in low bioavailability as they are mainly absorbed from the stomach and the lower part of the gastrointestinal tract. The bioavailability of antidiabetic drugs can be significantly increased by enhancing the gastric residence time using gastroretentive drug delivery systems such as floating microspheres.
Objectives: The present investigation deals with the development and optimization of floating microspheres for gastroretentive delivery containing repaglinide using Box-Behnken design and also investigates the effect of different process variables on the formation of the microsphere. Thereby, increasing the bioavailability and reducing the mentioned side effects of repaglinide.
Materials and methods: Floating microspheres of repaglinide formulated by ionic gelation method and optimized using Box-Behnken design. The independent variables were the concentration of Hydroxy methylcellulose (HPMC) (A), Sodium alginate (B), and calcium chloride (C) while entrapment efficiency (R1), swelling index (R2), and in vitro drug release (R3) were considered as dependent variables. The optimized formulation of floating microspheres was characterized by various physicochemical properties, surface morphology, drug excipient interaction, in vitro release, and buoyancy studies.
Results: Based on obtained 3D response surface plot factors A, B, and C were found to give a synergistic effect on R1, while factor A has a negative effect on R2. Interaction of AC was negative on R1 and R2 but positive on R3. The interaction of AC and BC was negative in all the responses. Scanning electron microscopy (SEM) revealed that microspheres were spherical with nearly smooth surface morphology. Good entrapment and buoyancy were observed for 12 h. The in vitro drug release was found to be controlled for more than 12 hours and followed the Higuchi model. The validations of response surface methodology (RSM) for three dependent variables were 100.09%, 99.68%, and 97.02%.
Conclusion: Repaglinide floating microspheres were prepared and optimized by use of Box – Behnken process optimization software. The quantitative responses of particle size, entrapment efficiency, and in vitro drug release for different combinations of independent variables, sodium alginate as release retarding polymer, HPMC K100M as floating polymer, and calcium chloride as a cross-linking agent were obtained experimentally, and the results were found to fit the design model. The quantitative effect of these factors at different levels on the responses could be predicted using polynomial equations, and high linearity was observed between predicted and actual values of response variables. The results of the present study showed that the responses i.e, particle size, entrapment efficiency, and in vitro release are significantly affected by the concentration of polymer and a cross-linking agent. The formulation OF1 was found to be the optimum formulation predicted by the point prediction of the design expert software. The in vitro drug release was found to be controlled for more than 12 h and followed the Higuchi model. The validations of RSM for three dependent variables were 100.09%, 99.68%, and 97.02%. Therefore, it can be concluded that a floating microsphere for repaglinide was developed and optimized using a three-factor, three-level Box – Behnken design.
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Keywords:
Box-Behnken design, Sodium alginate, Floating microspheres, Solvent evaporation
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A Gaur PK, Mishra S, Kumar A, Panda BP. Development and optimization of gastroretentive mucoadhesive microspheres of gabapentin by Box– Behnken design. Artif Cells Nanomedicine Biotechnol. 2014 Jun;42(3):167–77.
Waterman KC. A Critical Review of Gastric Retentive Controlled Drug Delivery. Pharm Dev Technol. 2007 Jan;12(1):1–10.
Hatorp V. Clinical Pharmacokinetics and Pharmacodynamics of Repaglinide: Clin Pharmacokinet. 2002;41(7):471–83.
Joshi G, Saini S, Arora S, Sharma A, Kumar V. Innovation in gastroretentive drug delivery systems: formulations and techniques for anti- diabetic drugs. Int J Adv Pharm. 2011;2(4):11.
M Sharma et al. In-vitro and in-vivo evaluation of repaglinide loaded floating microspheres prepared from different viscosity grades of HPMC polymer. Res Artic. 2015;23(6):675–82.
Ganesan P, Deepa John AJ, Sabapathy L, Duraikannu A. Review on Microsphere. Am J Drug Discov Dev. 2014 Jun 15;4(3):153–79.
K Vinchurkar et al. Features & Facts of Gastroretentive Drug Delivery System – A Review. Turk J Pharm Sci. 2021 Jun 18;1–21.
Yeole PG et al. Floating drug delivery systems: need and development. Indian JPharm Sci. 2004;3(67):265–72. 3
Soliman M, Elmowafy E, Almogerbi A, Mansour S. Dual buoyant/mucoadhesive macroporous polypropylene microparticles for gastric delivery of Repaglinide. Int J Drug Deliv. 2016;7(4):197–207.
Metkari VB, Kulkarni LV, Patil PS, Jadhav PA, Bamane GS, Kumbhar CM. Microspheres - A New Drug Delivery System: A Review. 2014;4(2):1128– 33.
Singh B et al. Developing micro-/nanoparticulate drug delivery systems using “design of experiments.” Rev Artic. 2011;1(2):75–87.
Chowdary KPR, Rao YS. Design and in vitro and in vivo evaluation of mucoadhesive microcapsules of glipizide for oral controlled release: A technical note. AAPS Pharm Sci Tech. 2003 Sep;4(3):87–92.
Prajapati SK, Tripathi P, Ubaidulla U, Anand V. Design and Development of Gliclazide Mucoadhesive Microcapsules: In Vitro and In Vivo Evaluation. AAPS PharmSciTech. 2008 Mar;9(1):224.
Chowdary KPR, Rao YS. Preparation-and- evaluation-of-mucoadhesive-microcapsules-of- indomethacin.pdf. Indian JPharm Sci. 2003;65(1):49–52.
Madhusudhan S, Panda AK, Parimalakrishnan S, Manavalan R, Manna PK. Design, in vitro and in vivo evaluation of glipizide Eudragit microparticles. J Microencapsul. 2010 Jan;27(4):281–91.
Abdallah MH. Box-behnken design for development and optimization of acetazolamide microspheres. Int J Pharm Sci Res. 2014;5(4):1228–39.
Andhariya JV, Burgess DJ. Recent advances in testing of microsphere drug delivery systems. Expert Opin Drug Deliv. 2016 Apr 2;13(4):593–608.
Vinchurkar K, Mane S, Balekar N, Jain DK. Formulation and evaluation of tablets containing artemether microspheres and lumefantrine. J Drug Deliv. 2017;7(7):4.
Patel AK, Mishra MK, Gupta J, Ghoshal S, Gupta R, Kushwaha K. Guar Gum-Based Floating Microspheres of Repaglinide Using 32Factorial Design: Fabrication, Optimization, Characteri-zation, and in Vivo Buoyancy Behavior in Albino Rats. ASSAY Drug Dev Technol. 2021 Mar 1;19(2):63–74.
Debraj D, Pal R. Formulation and Evaluation of RSM Based Floating Alginate Microspheres of Gymnemic Acid & In Vitro-In Vivo Correlation (IVIVC) for Treatment of Diabetes Mellitus. Int J Res Advent Technol. 2019 Apr 10;7(4):138–57.
NR Naveen et al. Design expert supported mathematical optimization of repaglinide gastroretentive floating tablets: In vitro and in vivo evaluation. Res Artic. 2017;3(2):140–7.
Dhole SM, Amnerkar ND, Khedekar PB. Comparison of UV spectrophotometry and high-performance liquid chromatography methods for the determination of repaglinide in tablets. Pharm Methods. 2012 Jul;3(2):68–72.
Nagarwal RC, Ridhurkar DN, Pandit JK. In Vitro Release Kinetics and Bioavailability of Gastroretentive Cinnarizine Hydrochloride Tablet. AAPS PharmSciTech. 2010 Mar;11(1):294–303.
Shah S, Qaqish R, Patel V, Amiji M. Evaluation of the Factors Influencing Stomach-specific Delivery of Antibacterial Agents for Helicobacter pylori Infection. J Pharm Pharmacol. 2010 Feb 18;51(6):667–72.
Okunlola A, Adebayo AS, Adeyeye MC. Development of repaglinide microspheres using novel acetylated starches of bitter and Chinese yams as polymers. Int J Biol Macromol. 2017 Jan;94((Pt A)):544–53.
Nandy BC et al. Preparation and evaluations of multi-particulates system of celecoxib: optimization
by response surface methodology. ASIO J Drug Deliv. 2015;1(1):11–25.
Prajapati S, Patel C, Patel L. Polymers for floating drug delivery system. Syst Rev Pharm. 2011;2(1):1– 7.
Subedi G, Shrestha AK, Shakya S. Study of Effect of Different Factors in Formulation of Micro and Nanospheres with Solvent Evaporation Technique. Open Pharm Sci J. 2016 Aug 9;3(1):182–95.
Prasad BSG, Gupta VRM, Devanna N, Jayasurya K. Microspheres as drug delivery system – a review. J Glob Trends Pharm. 2014;5(3):1961–72.
Vijay Bahadur K, Chhitij T, Prakash G, Pradyumna C, Jitendra Y. Formulation and optimization of Enalapril Maleate-loaded floating microsphere using Box–Behnken design: in vitro study. J Appl Pharm Sci. 2020 Aug 4;10(8):95–104.
Szekalska M, Sosnowska K, Czajkowska-Kośnik A, Winnicka K. Calcium Chloride Modified Alginate Microparticles Formulated by the Spray Drying Process: A Strategy to Prolong the Release of Freely Soluble Drugs. Materials. 2018 Aug 24;11(9):1522.
