Drug Res (Stuttg) 2021; 71(04): 204-212
DOI: 10.1055/a-1324-2466
Original Article

Formulation and Characterization of Losartan Loaded Chitosan Microspheres: Effect of Crosslinking Agents

Sonia Pahuja
1   Department of Pharmaceutics, Swami Vivekanand College of Pharmacy, Banur, Patiala, Punjab, India
,
Shweta Aggarwal
1   Department of Pharmaceutics, Swami Vivekanand College of Pharmacy, Banur, Patiala, Punjab, India
,
1   Department of Pharmaceutics, Swami Vivekanand College of Pharmacy, Banur, Patiala, Punjab, India
› Author Affiliations
Funding: We are also indebted towards management of Swami Vivekanand Group of Institutions (SVGOI) for providing financial support and conducible environment to carry out the current research project.

Abstract

Objective The present investigation entailed determination of effect of diverse cross-linking agents on Losartan Potassium loaded chitosan microspheres. The emulsion cross-linking method was employed to formulate the microspheres with an endeavour to achieve maximum sustained effect.

Methods The FTIR studies revealed absence of any interaction between Losartan and chitosan. The emulsion cross linking method was accomplished in three steps encompassing formation of an aqueous and oily phase, emulsification and cross-linking. A total of eighteen Losartan formulations were developed using six different cross-linkers at three varying level were screened for optimum parameters. The in vitro drug release parameters of optimum formulations (LC3, LE3, LF3, LG3, LS3 and LV3) containing citric acid, epichlorohydrin, formaldehyde, glutaraldehyde, suphuric acid and vanillin as cross-linkers were assessed to determine the sustained effect.

Results The values of evaluated parameters including percent yield (94.67%), average particle size (51.19 µm), drug content (44.38 mg) and entrapment efficiency (88.77%) connoted LG3 as the best formulation. Additionally, the values of relative measure of skewness (β1=0.01 and γ1=0.10) and platykurtic (β2=1.26) size distribution were least for LG3 with spherical shape and smooth surface as revealed by SEM studies.

Conclusion The outcome of in vitro release and other characterizations of microspheres explicitly revealed glutaraldehyde as the best cross-linker amongst the cross-linkers used herewith. The maximum sustained effect (lasting over a period of 24 h) accompanied with higher MDT and t50% with lower%DE and Q14h values thus corroborated the objective of attaining sustained release of Losartan.

Supplementary Material



Publication History

Received: 27 July 2020

Accepted: 23 November 2020

Article published online:
21 December 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Ren l, Xu J, Zhang Y. et al. Preparation and characterization of porous chitosan microspheres and absorption performance for hexavalent chromium. Int J Biol Macromol 2019; 135: 898-906
  • 2 Pandey J, Shankar R, Kumar M. et al. Development of nasal mucoadhesive microspheres of granisetron: A potential drug. 2020. Drug Res (Stuttg) 2020; 70: 367-375
  • 3 Li W, Ba H, Huang P. et al. Preparation and properties of 5-fluorouracil-loaded chitosan microspheres for the intranasal administration. Drug Res 2018; 68: 673-679
  • 4 Li C, Bo L, Li P. et al. Losartan, a selective antagonist of AT1 receptor, attenuates seawater inhalation induced lung injury via modulating JAK2/STATs and apoptosis in rat. Pulm Pharmacol Ther 2017; 45: 69-79
  • 5 Madgulkar A, Bhelekar M, Swami M. In vitro and in vivo studies on chitosan beads of losartan duolite AP 143 complex, optimized by using statistical experimental design. AAPS Pharm Sci Tech 2009; 10: 743-751
  • 6 Aggarwal S, Pahuja S. Pharmaceutical relevance of crosslinked chitosan in microparticulate drug delivery. Int Res J Pharm 2013; 4: 45-51
  • 7 Atangana E, Chiweshe TT, Roberts H. Modification of novel chitosan-starch cross-linked derivatives polymers: Synthesis and characterization. J Polym Environ 2019; 27: 979-995
  • 8 Pereira AKDS, Reis DT, Barbosa KM. et al. Antibacterial effects and ibuprofen release potential using chitosan microspheres loaded with silver nanoparticles. Carbohydr Res 2020; 488: 107891
  • 9 Zou Q, Li J, Li Y. Preparation and characterization of vanillin-crosslinked chitosan therapeutic bioactive microcarriers. Int J Biol Macromol 2015; 79: 736-747
  • 10 Goncalves VL, Laranjeira MCM, Favere VT. et al. Effect of crosslinking agents on chitosan microspheres in controlled release of diclofenac sodium. Polímeros 2005; 15: 6-12
  • 11 Yu Z, Dang Q, Liu C. et al. Preparation and characterization of poly(maleic acid)-grafted cross-linked chitosan microspheres for Cd (II) absorption. Carbohydr Polym 2017; 172: 28-39
  • 12 Zhang Q, Tian JH, Liu TL. et al. Preparation and antibacterial properties of carboxymethyl chitosan/Zno nanocomposite microspheres with enhanced biocompatibility. Mater Lett 2018; 212: 58-61
  • 13 Zang W, Li Q, Mao Q. et al. Cross-linked chitosan microspheres: An efficient and eco- friendly absorbent for iodide removal for waste water. Carbohydr Polym 2019; 206: 215-222
  • 14 Wang E, Wang X, Wang K. et al. Preparation, characterization and evaluation of the immune effect of alginate/chitosan composite microspheres encapsulating recombinant protein of Streptococcus iniae design for fish oral vaccination. Fish Shellfish Immunol 2018; 73: 262-271
  • 15 Jin M, Zheng Y, Hu Q. Preparation and characterization of bovine serum albumin alginate/chitosan microspheres for oral administration. Asian J Pharm Sci 2009; 4: 215-220
  • 16 Patil SV, Sahoo SK, Behera AL. Preparation and in vitro characterization of oral sustained release chitosan coated cefepime hydrochloride microspheres. Int J Pharm Tech Res 2010; 2: 798-803
  • 17 Zhu T, Zhu T, Gao J. et al. Enhanced absorption of fluoride by cerium immobilized cross-linked chitosan composite. J Fluorine Chem 2017; 194: 80-88
  • 18 Nayak S, Hetal P, Rajesh K. et al. Colon delivery of 5-fluoro uracil cross-linked chitosan microspheres coated with eudragit S 100. Int J Drug Delivery 2011; 3: 260-268
  • 19 Roy S, Panpalia SG, Nandy BC. et al. Effect of method of preparation on chitosan microspheres of mefenamic acid. Int J Pharm Sci and Drug Res 2009; 1: 36-42
  • 20 Cutrignelli A, Trapani A, Lopedota A. et al. Griseofulvin/Carrier Blends: Application of Partial Least Squares (PLS) Regression Analysis for Estimating the Factors Affecting the Dissolution Efficiency. AAPS Pharm Sci Tech 2011; 12: 1019-1030
  • 21 Moin A, Shivakumar HG. Formulation of sustained release diltiazem matrix tablets using hydrophilic gum blends. Trop J Pharm Res 2010; 9: 283-291
  • 22 Zhang Y, Hou M, Zhou J. DDSolver: An Add-In program for modeling and comparison of drug dissolution profiles. AAPS J 2010; 12: 263-271
  • 23 Ganesh NS. Dr. Deecarman Chronomodulated drug delivery system of lornoxicam using natural polymers. J Pharm Res 2011; 4: 825-828
  • 24 Ghosh A, Nayak UK, Rout P. et al. Preparation, Evaluation and in vitro in vivo correlation study of lumivudine loaded microspheres. Res J Pharm Technol 2008; 1: 353-356
  • 25 Patil SB, Murthy RSR. Preparation and in vitro evaluation of mucoadhesive chitosan microspheres of amlodipine besylate for nasal administration. Ind J Pharm Sci 2006 68: 64-67
  • 26 Gupta SC, Kapoor VK. Fundamental of Mathematical Statistics. New Delhi: Sultan Chand & Sons; 2010
  • 27 Leung SHS, Robinson JR. The contribution of anionic polymer structural features to mucoadhesive. J Controlled Release 1988; 5: 223-231
  • 28 Yurdasiper A, Sevgi F. An overview of modified release chitosan, alginate and eudragit RS microparticles. J Chem Pharm Res 2010; 2: 704-721
  • 29 Oreinti I, Aiedeh K, Gianasi E. et al. Indomethacin loaded chitosan microspheres correlation between the erosion process and release kinetics. J Microencapsulation 1996; 13: 463-492
  • 30 Cui Z, Xiang Y, Jiangju S. et al. Ionic interactions between sulfuric acid and chitosan membranes. Carbohydr Polym 2008; 73: 111-116
  • 31 Sedyakina N, Kuskov A, Velonia K. et al. Modulation of Entrapment Efficiency and In Vitro Release Properties of BSA-Loaded Chitosan Microparticles Cross-Linked with Citric Acid as a Potential Protein-Drug Delivery System. Materials (Basel) 24.04.2020; 13: 1989 DOI: 10.3390/ma13081989.
  • 32 Emami J. Comparative in vitro and in vivo evaluation of three tablet formulations of amiodarone in healthy subjects. Daru, J Pharm Sci 2010; 18: 193-198
  • 33 Gande S, Rao YM. Sustained release effervescent floating matrix tablets of baclofen: development, optimization and in vitro-in vivo evaluation in healthy human volunteers. Daru, J Pharm Sci 2011; 19: 202-208
  • 34 Patel M, Pandya N, Vasanti S. et al. Mucoadhesive repaglinide microspheres for gastric delivery: Formulation and in-vitro characterization. Indian Drugs 2009; 46: 310-313
  • 35 Varshosaz J, Alinagari R. Effect of Citric Acid as Cross-linking Agent on Insulin Loaded Chitosan Microspheres. Iranian Polym J 2005; 14: 647-656
  • 36 Kosmeyer RW, Gurny R, Doelker E. et al. Mechanisms of potassium chloride release from compressed hydrophilic, polymeric matrices: Effect of entrapped air. J Pharm Sci 1983; 72: 1189-1191
  • 37 Yuce M, Canefe K. Indomethacin-loaded microspheres: preparation, characterization and in-vitro evaluation regarding ethylcellulose matrix material. Turk J Pharm Sci 2008; 5: 129-142