QBD-BASED DEVELOPMENT AND EVALUATION OF ENTERIC COATED MUCOADHESIVE MICROCAPSULES OF AMOXICILLIN TRIHYDRATE AS A NOVEL CHRONOTHERAPEUTIC APPROACH FOR TREATMENT OF BACTERIAL INFECTIONS
Objective:Â The present work entails design and characterization of enteric coated mucoadhesive microcapsules loaded with amoxicillin trihydrate as a novel chronotherapeutic approaches for the treatment and management of bacterial infection.
Methods:Â The microcapsules were prepared by solvent evaporation technique using ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) as rate-controlling and mucoadhesive polymers, followed by a triple coating with Eudragit L100 as enteric coating polymer. Box-Behnken statistical design (BBD) was applied for optimization of formulations containing EC, HPMCK100M and Eudragit L100 as factors for selected responses like entrapment efficiency, mucoadhesive property and drug release in 24 h. The optimized microcapsules were also characterized for particle size, drug content, swelling index, mucoadhesive strength, andÂ in vivoÂ antiulcer activity.
Results:Â The optimized microcapsules exhibited good entrapment efficiency, particle size and mucoadhesive property. FT-IR studies revealed that there was no drug-polymer interaction. SEM studies revealed that microcapsules were non-aggregated, spherical in shape and smooth appearance.Â In vitroÂ drug release data from microcapsules was fitted to different kinetic models to explain release profiles. The correlation coefficient (r2) value indicated that drug release followed Higuchi model. Analysis of variance (ANOVA) showed significant difference in the release of drug from all the prepared formulations atÂ P < 0.05Â level. Accelerated stability study of optimized formulation (F4) upto 6 month showed there was no change in drug content and release characteristics during storage.
2. Kalantzi LE, Evangelos K, Koutris EX, Bikaris DN. Recent advances in oral pulsatile drug delivery. Recent Pat Drug Delivery Formul 2009:3:49-63.
3. Hommura Y, Sakamoto Y, Matsukawa J, Shinkawa A. Clinical study on amoxicillin in the otorhinolaryngological field. Japan J Antibiot 1975;28:353-62.
4. Stillerman M, Isenberg HD, Kacklam RR. Treatment of pharyngitis associated with a group a streptoccous: comparison of amoxicillin and potassium phenoxymethyl-penicillin. J Infect Dis 1974;129:69-77.
5. Sherwood PV, Wibawa JI, Atherton JC, Jordan N, Jenkins D, Barrett DA, et al. Impact of acid secretion, gastritis, and mucus thickness on the gastric transfer of antibiotics in rats. Gut 2002;51:490-5.
6. USP 34-NF 29. Available from: http://www.usp.org/USPNF. [Last accessed on 08 Feb 2011].
7. Amoxicillin. Available from: http://en.wikipedia.org/wiki/ Amoxicillin. [Last accessed on 08 Feb 2011].
8. Beauchampa D, Labrecque G. Chronobiology and chronotoxicology of antibiotics and aminoglycosides. Adv Drug Delivery Rev 2007;59:896-903.
9. Breese BB, Disney FA, Talpey WB, Green JL. Treatment of streptococcal pharyngitis with amoxicillin. J Infect Dis 1974;129:78-80.
10. Beg S, Swain S, Gahoi S, Kohli K. Design, development and evaluation of chronomodulated drug delivery systems of amoxicillin trihydrate with enhanced antimicrobial activity. Curr Drug Delivery 2013;10:174-87.
11. Khan M, Ansari VA, Kushwaha P, Kumar A, Akhtar J. Mucoadhesive microspheres for controlled delivery of drugs. Asian J Pharm Clin Res 2015;8:17-20.
12. Helliwell M, Lim ST. The use of bioadhesives in targeted delivery. J Controlled Release 2000;16:281-90.
13. Najmuddin M, Shelar S, Ali A, Patel V, Khan T. Formulation and in vitro evaluation of floating microspheres of ketoprofen prepared by the emulsion solvent diffusion method. Int J Appl Pharm 2010;2:13-7.
14. Ace F, Pallotta S, Casalini S, Gabriele BP. A review of rabeprazole in the treatment of acid-related diseases. Ther Clin Risk Manag 2007;3:363-79.
15. Alli SMA, Ali SMA, Samanta A. Development and evaluation of intestinal targeted mucoadhesive microspheres of Bacillus coagulans. Drug Dev Indian Pharm 2011;37:1329-38.
16. Liu YH, Zhu X, Zhou D, Jin Y, Zhao CY, Zhang ZR, et al. pH-sensitive and mucoadhesive microspheres for duodenum-specific drug delivery system. Drug Dev Ind Pharm 2011;37:868-74.
17. Sachan NK, Bhattacharya A. Basics and therapeutic potential of oral mucoadhesive microparticulate drug delivery systems. Int J Pharm Clin Res 2009;1:10-4.
18. Rowe RC, Sheskey RJ, Weller PJ. Handbook of pharmaceutical excipients. 4th Ed. Pharmaceutical Press; 2003. p. 237-41.
19. Singh B, Kumar R, Ahuja N. Optimizing drug delivery systems using systematic â€œdesign of experiments.â€ Part I: fundamental aspects. Crit Rev Ther Drug Carrier Syst 2005;22:27-105.
20. Singh B, Dahiya M, Saharan V, Ahuja N. Optimizing drug delivery systems using systematic â€œdesign of experiments.â€ Part II: retrospect and prospects. Crit Rev Ther Drug Carrier Syst 2005;22:215-94.
21. Gohel MC, Amin AF. Formulation design and optimization of modified-release microspheres of diclofenac sodium. Drug Dev Ind Pharm 1999;25:247-51.
22. Chawla V, Tiwary AK, Gupta S. Characterization of polyvinylalcohol microspheres of diclofenac sodium: application of statistical design. Drug Dev Ind Pharm 2000;26:675-80.
23. Nayak BS, Ghosh SK, Tripati K, Patro B. Preparation and characterization of famotidine microcapsule employing mucoadhesive polymers in combination to enhance gastro retention for oral delivery. Int J Pharm Sci 2009;1:112-20.
24. Dandagi PM, Mastiholimath VS, Gadad AP, Iliger SR. Mucoadhesive microspheres of propranolol hydrochloride for nasal delivery. Indian J Pharm Sci 2007;69:402-7.
25. Abu Izza K, Garcia LC, Robert D. Preparation and evaluation of zidovudine loaded sustained release microspheres optimization of multiple response variables. J Pharm Sci 1996; 85:572-4.
26. Soppimath KS, Kulkarni AR, Aminabhavi TM. Development of hollow microspheres as floating controlled release systems for cardiovascular drugs: preparation and release characteristics. Drug Dev Ind Pharm 2001;27:507-15.
27. Arya RKK, Vijay JA, Singh R. Development and evaluation of gastroresistant microspheres of pantoprazole. Int J Pharm Pharm Sci 2010;2:1575-80.
28. Muzaffar F, Murthy NV, Paul P, Semwal R, Pandy S. Formulation and evaluation of mucoadhesive microspheres of amoxicillin trihydrate by using Eudragit RS 100. Int J Chem Tech Res 2010;2:466-70.
29. 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;4:1-6.
30. Sankalia JM, Sankalia MG, Mashru RC. Drug release and swelling kinetics of directly compressed glipizide sustained-release matrices: establishment of level A IVIVC. J Controlled Release 2008;129:49-58.
31. Syed IA, Narsu ML, Rao YM. In vitro release kinetics and bioavailability of oral controlled release layered matrix tablets of diltiazem hydrochloride. Int J Drug Dev Res 2011;3:234-41.