FLOATING RANITIDINE MICROPARTICULATES: DEVELOPMENT AND IN VITRO EVALUATION
Objective: Rapid and inconsistent gastrointestinal tract (GIT) transit could result in reduced drug efficiency and the need for frequent dose administration, which usually result in patientsâ€™ incompliance. Ranitidine hydrochloride (RH), as a model drug is freely soluble, moisture sensitive drug with a short biological half-life (~2.5-3 h) and narrow absorption window in the initial part of the small intestine. The present study aimed to develop ranitidine floating multi-particulates (RFM) using melt granulation technique and investigation of the effect of lipids and additives on the physicochemical properties.
Methods: RFM were prepared using CompritolÂ® 888 ATO, glyceryl behenate, CutinaÂ® HR, CutinaÂ® GMS, hydrogenated castor oil, glyceryl monostearate, and beeswax as lipids and ethyl cellulose, PovidoneÂ® K 90 and AerosilÂ® 200 as release modifiers. The effect of the preparation method and additives, as well as storage for 6 mo at 40 Â°C, on floating and release characteristics were evaluated.
Results: Size distribution indicated that the prepared formulations exhibited reasonably small floating micro particulates; more than 90% of the prepared microparticles were less than 710 Âµm. Hausner ratios and Carrâ€™s compressibility indices ranged from 1.17 to 1.29% and 14.54 to 22.4 %, respectively, and the angle of repose values was â‰¤40 Â°, indicating good flow properties. RFM containing CompritolÂ® showed a relatively higher release properties compared to hydrogenated castor oil. Increasing the proportion of the fatty component was accompanied by retardation in RH release. The tested additives (PVP, ethyl cellulose, AerosilÂ®) resulted in different degrees of retardation of drug release. The percent-floating of RFM was almost 100% in all formulations with the exception of formulations prepared using glyceryl monostearate. FT-IR and DSC studies indicated the compatibility of the excipients with RH. Stability results revealed an insignificant change in RFM properties over 6 mo.
Conclusion: The prepared microparticles exhibited optimum particle size, good compressibility, and flow properties. RFM containing CompritolÂ® showed a relatively higher release properties compared to hydrogenated castor oil. Increasing the proportion of the fatty component was accompanied by retardation in RH release. The percent-floating of RFM was almost 100% in most formulations. FT-IR and DSC indicated good compatibility of the excipients with RH and insignificant change in RFM properties over 6 moâ€™s storage.
2. Fukuda M, Goto A. Properties of gastro retentive sustained release tablets prepared by a combination of melt/sublimation actions of L-menthol and penetration of molten polymers into tablets. Chem Pharm Bull 2011;59:1221-6.
3. Hoffman A, Stepensky D, Lavy E, Eyal S, Klausner E, Friedman M. Pharmacokinetic and pharmacodynamic aspects of gastro retentive dosage forms. Int J Pharm 2004;277:141-53.
4. Streubel A, Siepmann J, Bodmeier R. Drug delivery to the upper small intestine window using gastro retentive technologies. Curr Opin Pharmacol 2006;6:501-8.
5. Jain S, Srinath MS, Narendra C, Reddy SN, Sindhu A. Development of a floating dosage form of ranitidine hydrochloride by statistical optimization technique. J Young Pharm 2010;2:342-9.
6. Shukla D, Chakraborty S, Singh S, Mishra B. Lipid-based oral multi-particulate formulations-advantages, technological advances, and industrial applications. Expert Opin Drug Delivery 2011;8:207-2.
7. Shimpi S, Chauhan B, Mahadik KR, Paradkar A. Preparation and evaluation of diltiazem hydrochloride-gelucire 43/01 floating granules prepared by melt granulation. AAPS PharmSciTech 2004;5:51-6.
8. Mu B, Thompson MR. Examining the mechanics of granulation with a hot melt binder in a twin-screw extruder. Chem Eng Sci 2012;81:46-56.
9. Dey N, Majumdar S, Rao M. Multiparticulate drug delivery systems for controlled release. Trop J Pharm Res 2008;7:1067-75.
10. Wen H, Park K. Oral controlled release formulation design and drug delivery: Theory to Practice. New Jersey: John Wiley and Sons, Inc; 2010. p. 1-350.
11. Lingam M, Ashok T, Venkateswarlu V, Madhusudan Rao Y. Design and evaluation of a novel matrix type multiple units as biphasic gastro retentive drug delivery systems. AAPS PharmSciTech 2008;9:1253-61.
12. Lauritsen K, Laursen LS, Rask-Madsen J. Clinical pharmacokinetics of drugs used in the treatment of gastrointestinal diseases (Part I). Clin Pharmacokinet 1990; 19:11-31.
13. Shakya R, Thapa P, Saha RN. In vitro and in vivo evaluation of gastro retentive floating drug delivery system of ofloxacin. Asian J Pharm Sci 2013;8:191-8.
14. Khan KA. The concept of dissolution efficiency. J Pharm Pharmacol 1975;27:48-9.
15. Roy P, Shahiwala A. Statistical optimization of ranitidine HCl floating pulsatile delivery system for chronotherapy of a nocturnal acid breakthrough. Eur J Pharm Sci 2009;37:363-9.
16. Shah RB, Tawakkul MA, Khan MA. Comparative evaluation of flow for pharmaceutical powders and granules. AAPS PharmSciTech 2008;9:250-8.
17. USP: USP 34 NF 29 The United States Pharmacopeial Convention; 2011 NF29, Rockville, USA; 2011.
18. Albertini B, Passerini N, Gonzalez-Rodriguez ML, Perissutti B, Rodriguez L. Effect of aerosil on the properties of lipid-controlled release microparticles. J Controlled Release 2004;100:233-46.
19. Bhalla S, Nagpal M. Comparison of various generations of super porous hydrogels based on chitosan-acrylamide and in vitro drug release. ISRN Pharm 2013:8. http:// dx.doi.org/10.1155/2013/624841
20. Wei YM, Zhao L. In vitro and in vivo evaluation of ranitidine hydrochloride loaded hollow microspheres in rabbits. Arch Pharm Res 2008;31:1369-77.
21. ICH Stability Guidelines [http://www.ich.org/products/ guidelines/ quality/article/quality-guidelines.html]. [Last accessed on 03 Mar 2016]