DESIGNING AND DEVELOPMENT OF GASTRORETENTIVE MUCOADHESIVE MICROSPHERES OF CEFIXIME TRIHYDRATE USING SPRAY DRYER

PRIYANKA CHATURVEDI; PRAKASH KUMAR SONI; SURESH KUMAR PASWAN

doi:10.22159/ijap.2023v15i2.45399

Authors

PRIYANKA CHATURVEDI Industrial Pharmacy Research Lab, Department of Pharmacy, Shri G. S. Institute of Technology and Science, 23, Park Road, Indore (M. P.) 452003 https://orcid.org/0000-0003-3780-7097
PRAKASH KUMAR SONI Industrial Pharmacy Research Lab, Department of Pharmacy, Shri G. S. Institute of Technology and Science, 23, Park Road, Indore (M. P.) 452003 https://orcid.org/0000-0002-2202-3778
SURESH KUMAR PASWAN Industrial Pharmacy Research Lab, Department of Pharmacy, Shri G. S. Institute of Technology and Science, 23, Park Road, Indore (M. P.) 452003 https://orcid.org/0000-0002-0030-0914

DOI:

https://doi.org/10.22159/ijap.2023v15i2.45399

Keywords:

Cefixime trihydrate, Mucoadhesive microsphere, Gastroretention, Spray drying

Abstract

Objective: Cefixime is a weakly acidic drug primarily absorbed through the stomach and upper intestinal part and has incomplete absorption in lower GIT which leads to its poor bioavailability. The current research work is aimed to develop gastroretentive mucoadhesive microspheres of cefixime to enhance absorption in the stomach.

Methods: Cefixime trihydrate mucoadhesive microspheres formulation was developed by spray drying technique and optimized by DoE approach using Box-Behnken design. The independent variables selected in the formulation were HPMC K15M (X₁) as carrier polymer, Carbopol 971P (X₂) as mucoadhesive polymer and Cefixime trihydrate (X₃). The response variables studied were mean particle size (R₁), and percent cumulative drug release at different time points (R₂-R₈). The optimized batch was evaluated for mucoadhesion properties, DSC and SEM analysis.

Results: The Ex-vivo test of cefixime microspheres studied on goat intestinal mucosa showed strong mucoadhesion of 82% for an extended period of 6 h. The in vitro drug release studies of microspheres in 0.1 N HCl showed extended release up to 8 h. The DSC thermograph indicated the conversion of the drug from crystalline form to amorphous form following the formation of solid dispersion. SEM analysis reveals the microspheres were spherical and smooth.

Conclusion: It is concluded from the above studies that the current formulation has increased gastric residence time and prolonged release for better absorption of the drug, thus, the formulation will have better therapeutic and increased bioavailability.

Downloads

Download data is not yet available.

References

Tan BJK. Cefixime use in children: when and why. Can J Infect Dis. 1995;6(4):204-5. doi: 10.1155/1995/170243, PMID 22514398.

Bhaskar R, Patil PH. Nanocrystal suspension of poorly water-soluble antibacterial drug by high-pressure homogenization technique using full factorial design. Int J Pharm Sci Res. 2018;9(1):114-22. doi: 10.13040/IJPSR.0975-8232.9(1).114-22.

Kandhro AA, Laghari AH, Mahesar SA, Saleem R, Nelofar A, Khan ST. Application of attenuated total reflectance Fourier transform infrared spectroscopy for determination of cefixime in oral pharmaceutical formulations. Spectrochim Acta A Mol Biomol Spectrosc. 2013;115:51-6. doi: 10.1016/j.saa.2013.06.032, PMID 23831978.saa.2013.06.032.

Maestrelli F, Jug M, Cirri M, Kosalec I, Mura P. Characterization and microbiological evaluation of chitosan-alginate microspheres for cefixime vaginal administration. Carbohydr Polym. 2018;192:176-83. doi: 10.1016/j.carbpol.2018.03.054, PMID 29691010.

Kumar M, Kaushik D. An overview on various approaches and recent patents on gastroretentive drug delivery systems. Recent Pat Drug Deliv Formul. 2018;12(2):84-92. doi: 10.2174/1872211312666180308150218, PMID 29521255.

Tripathi J, Thapa P, Maharjan R, Jeong SH. Current state and future perspectives on gastroretentive drug delivery systems. Pharmaceutics. 2019;11(4). doi: 10.3390/ pharmaceutics11040193, PMID 31010054.

Hussain T, Ijaz M, Shamim R, Hussain K, Abbas N, Hussain A. In vivo evaluation of a novel chitosan-polycaprolactone-based mucoadhesive gastro-retentive sustained release drug delivery system for milnacipran HCl. AAPS PharmSciTech. 2020;21(2):58. doi: 10.1208/s12249-019-1606-6, PMID 31912249.

Srivastava A, Verma A, Saraf S, Jain A, Tiwari A, Panda PK. Mucoadhesive gastroretentive microparticulate system for programmed delivery of famotidine and clarithromycin. J Microencapsul. 2021;38(3):151-63. doi: 10.1080/02652048.2020.1851787, PMID 33205689.

Hanif M, Shah S, Rasul A, Abbas G, Zaman M, Amjad MW. Enhancement of oral bioavailability of ibandronate through gastroretentive raft forming drug delivery system: in vitro and in vivo evaluation. Int J Nanomedicine. 2020;15:4847-58. doi: 10.2147/IJN.S255278. PMID 32764922.

Sunoqrot S, Hasan L, Alsadi A, Hamed R, Tarawneh O. Interactions of mussel-inspired polymeric nanoparticles with gastric mucin: implications for gastro-retentive drug delivery. Colloids Surf B Biointerfaces. 2017;156:1-8. doi: 10.1016/j.colsurfb.2017.05.005. PMID 28499200.

Salatin S, Jelvehgari M. Expert design and optimization of ethyl cellulose-poly (ε-caprolactone) blend microparticles for gastro-retentive floating delivery of metformin hydrochloride. Curr Drug Deliv. 2021;18(8):1125-35. doi: 10.2174/1567201818666210204164145, PMID 33563167.

Paswan SK, Saini TR, Jahan S, Ganesh N. Designing and formulation optimization of hyaluronic acid conjugated plga nanoparticles of tamoxifen for tumor targeting. Pharm Nanotechnol. 2021;9(3):217-35. doi: 10.2174/2211738509666210310155807, PMID 33745427.

Kaoud RM, Heikal EJ, Hammady TM. Diacerein-loaded niosomes (DC-NS): A new technique to sustain the release of drug action. Int J App Pharm. 2022;14(1):156-63. doi: 10.22159/ijap.2022v14i1.43353.

Stenger Moura FC, Perioli L, Pagano C, Vivani R, Ambrogi V, Bresolin TM. Chitosan composite microparticles: A promising gastro adhesive system for taxifolin. Carbohydr Polym. 2019;218:343-54. doi: 10.1016/j.carbpol.2019.04.075, PMID 31221339.

Mulia K, Singarimbun AC, Krisanti EA. Optimization of chitosan-alginate microparticles for delivery of mangostins to the colon area using box-Behnken experimental design. Int J Mol Sci. 2020;21(3). doi: 10.3390/ijms21030873, PMID 32013253.

Sisinthy SP, Rao NK, Sarah CYL. Design, optimization and in vitro characterization of self-nano emulsifying drug delivery system of olmesartan medoxomil. Int J Pharm Pharm Sci. 2017;9(1):94-101. doi: 10.22159/ijpps.2017v9i1.15166.

Kurra P, Narra K, Puttugunta SB, Kilaru NB, Mandava BR. Development and optimization of sustained-release mucoadhesive composite beads for colon targeting. Int J Biol Macromol. 2019;139:320-31. doi: 10.1016/j.ijbiomac.2019.07.190, PMID 31374273.

Kashif PM, Madni A, Ashfaq M, Rehman M, Mahmood MA, Khan MI. Development of eudragit RS 100 microparticles loaded with ropinirole: optimization and in vitro evaluation studies. AAPS PharmSciTech. 2017;18(5):1810-22. doi: 10.1208/s12249-016-0653-5, PMID 27830514.

Jusu SM, Obayemi JD, Salifu AA, Nwazojie CC, Uzonwanne V, Odusanya OS. Drug-encapsulated blend of PLGA-PEG microspheres: in vitro and in vivo study of the effects of localized/targeted drug delivery on the treatment of triple-negative breast cancer. Sci Rep. 2020;10(1):14188. doi: 10.1038/s41598-020-71129-0, PMID 32843673.

Tao Y, Lu Y, Sun Y, Gu B, Lu W, Pan J. Development of mucoadhesive microspheres of acyclovir with enhanced bioavailability. Int J Pharm. 2009;378(1-2):30-6. doi: 10.1016/j.ijpharm.2009.05.025, PMID 19465102.

Wong TW, Chan LW, Lee HY, Heng PWS. Release characteristics of pectin microspheres prepared by an emulsification technique. J Microencapsul. 2002;19(4):511-22. doi: 10.1080/02652040210140481, PMID 12396387.

Gaba P, Singh S, Gaba M, Gupta GD. Galactomannan gum coated mucoadhesive microspheres of glipizide for treatment of type 2 diabetes mellitus: in vitro and in vivo evaluation. Saudi Pharm J. 2011;19(3):143-52. doi: 10.1016/j.jsps.2011.02.001. PMID 23960752.

Madgulkar AR, Bhalekar MR, Kadam AA. Improvement of oral bioavailability of lopinavir without co-administration of ritonavir using microspheres of thiolated xyloglucan. AAPS PharmSciTech. 2018;19(1):293-302. doi: 10.1208/s12249-017-0834-x, PMID 28717974.

Velmurugan S, Ali MA. Preparation and evaluation of maraviroc mucoadhesive microspheres for gastro retentive drug delivery. Int J Pharm Pharm Sci. 2015;7(5):208-14.

Liu Y, Zhang J, Gao Y, Zhu J. Preparation and evaluation of glyceryl monooleate-coated hollow-bioadhesive microspheres for gastroretentive drug delivery. Int J Pharm. 2011;413(1-2):103-9. doi: 10.1016/j.ijpharm.2011.04.030, PMID 21540088.

Dandagi PM, Mastiholimath VS, Gadad AP, Iliger S. Mucoadhesive microspheres of propranolol hydrochloride for nasal delivery. Indian J Pharm Sci. 2007;69(3). doi: 10.4103/0250-474X.34550.

Dhakar RC, Maurya SD, Sagar BPS, Bhagat S, Prajapati SK, Jain CP. Variables influencing the drug entrapment efficiency of microspheres: A pharmaceutical review. Pharm Lett. 2010;2(5):102-16.

Paul Y, Kumar M, Singh B. Formulation and in vitro evaluation of gastroretentive drug delivery system of cefixime trihydrate. Int J Drug Dev Res. 2010;3(4):148-61.

Prasad GR, Indira S, Shastri N, Sadanandam M. Formulation and in vitro evaluation of cefixime gastroretentive drug delivery system. Res J Pharm Technol. 2014;7(1):29-33.

Niharika MG, Krishnamoorthy K, Akkala M. Overview on floating drug delivery system. Int J App Pharm. 2018;10(6):65-71. doi: 10.22159/ijap.2018v10i6.28274.