GASTRORETENTIVE NIZATIDINE LOADING MICROBALLOONS FOR TREATMENT OF PEPTIC ULCER
Objective: The aim of the present work was to formulate a controlled release dosage form of water soluble drug such as Nizatidine to increase its gastric retention in the stomach and consequently, enhance its absorption and improve its bioavailability.
Methods: Microballoons were prepared by emulsion non solvent evaporation method using ethyl cellulose 7 CP in different ratios. The prepared microballoons were evaluated for yield percentage, entrapment efficiency, in vitro buoyancy and in vitro dissolution.
Results: Results showed that as drug to polymer ratio increased from 1:1 to 1:5 yield percentage, entrapment efficiency, in vitro buoyancy increased from 70.4+1.5 to87.2+1.8, from 71.5+2.1 to 90.2+2.6 and from 82.1+3.2 to 93.2+2.6, respectively, while the amount of drug released decreased from 88.1+2.1 to 68.9+1.8. When stirring rate increased from 800 rpm to 1600 rpm, the three parameters decreased from 93.2+2.7 to 81.5, from 96.4+3.5 to 82.6+1.7 and from 97+5.4 to 88.2+4.1, respectively, while the amount released increased from 63.1+2.6 to 73.8+1.2. When Span 80 concentrations increased from 0.1% to 2% the three parameters decreased from 95.2+2.6, to 81.6+3.2, from 97.6+1.8 to 82.4+1.8 and from 97.3+5.2 to 89.1+4.6, respectively, and the amount released percentage increased from 61.2+2.6 to 76.1+1.6. All drug release showed Higuchi diffusion models. The increase in the mean Tmax and the decrease in the mean Cmax of microballoons compared to the plain drug indicate a sustained release of microballoons and reflects a high improvement in its bioavailability.
Conclusion: It is evident from this study that microballoons are promising gastric prolonging the delivery system for nizatidine and have good stability.
2. Gholap SB, Banarjee SK, Gaikwad DD, Jadhav SL, Thorat RM. Hollow microspheres a review. Int J Pharm Sci 2010;1:74-9.
3. Dehghan M, Khan FN. Gastroretentive drug delivery systems: a patent perspective. Int J Health Res 2009;2:23-44.
4. Basit AW, Newton JM, Lacey LF. Susceptibility of the H2-receptor antagonists' cimetidine, famotidine and nizatidine to metabolism by gastrointestinal microflora. Int J Pharm 2002;23:23-33.
5. Pande AV, Vaidya PD, Arora A, Dhoka MV. In vitro and In vivo evaluation of ethylcellulose floating microspheres of cefpodoxime proxetil. Int J Pharm Biomed Res 2010;1:122-8.
6. Patel A, Ray S, Thakur RS. In vitro evaluation and optimization of controlled release floating drug delivery system of metformin hydrochloride. Daru J Pharm Sci 2006;14:57-64.
7. Yogesh GS, Durgacharan BA, Akhil MP. Formulation and evaluation of intra gastric floating drug delivery system of diltiazem hydrochloride. Asian J Pharm 2008;2:228-31.
8. Sato Y, Kawashima Y, Takeuchi H, Yamamoto H. Physicochemical properties to determine the buoyancy of hollow microspheres (Microballon) prepared by the emulsion solvent dffusion method. Eur J Pharm Biopharm 2003;55:297-304.
9. Tanwar YS, Naruka PS, Ojha GR. Development and evaluation of floating microspheres of verapamil hydrochloride. Braz J Pharm Sci 2007;43:529-34.
10. Pujara ND, Patel NV, Thaker AP, Raval BK, Doshi SM, Parmar RB. Floating microspheres: a novel approach for gastroretention. World J Pharm Pharm Sci 2012;1:872-95.
11. Bharate SP, Rupnvar YS, Sonvane RM, Pawar KR, Rahane RD. Formulation and Evaluation of floating microspheres of ketroloac trometamol. Int J Pharm Res Dev 2009;9:1-8.
12. United States pharmacopoeia XXIV NF XIX; 2000.
13. Shaji S, Pasha ST, Srinivasan S, Ray S. Design and optimization of a multiparticulate gastroretentive dosage form for better control of gastric acidity. J Pharm Sci Tech 2009;1:40-7.
14. Manish PP, Patel MM, Patel KN, Patel DR, Patel UL. Designing and evaluation of floating microspheres of verapamil hydrochloride: effect of methocel. Res J Pharm Dosage Forms Tech 2009;1:22-8.
15. Zaraghi A, Foroutan SM, Shafaati A, Khoddam A. Validated HPLC method for determination of Amlodipine in human plasma and its application to pharmacokinetic studies. Farmaco 2005;60:789-92.
16. Cakar MB, Ulu ST. HPLC fluorescence method for determination of nizatidine in human plasma and its application to pharmacokinetic study. Luminescence 2014;29:357-61.
17. Meyyanthan SN, Muralidhar S, Rajan S, Gopal K, Suresh B. A simple sample preparation with HPLC-UV metod for estimation of Amlodipine from plasma: Application to bioequivalence study. Open Chem Biomed Methods J 2008;1:22-7.
18. Higuchi T. Mechanism of sustained action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci 1963;52:1145-9.
19. Garg R, Gupta GD. Gastro retentive floating microspheres of silymarin: preparation and In vitro evaluation. Trop J Pharm Res 2010;9:59-66.
20. Srivastava AK, Ridhurkar DN, Wadhwa S. Floating microspheres of cimetidine: Formulation, Characterization and In-Vitro evaluation. Acta Pharm 2005;55:277-85.
21. Najmuddin M, Ahmed A, Shelar S, Patel V, Khan T. Floating microspheres of ketoprofen: formulation and evaluation. Int J Pharm Pharm Sci 2010;2:164-8.
22. Gadad A, Naval C, Patel k, Dandagi P, Mastiholimath V. Formulation and evaluation of floating microspheres of captopril for prolonged gastric residence time. Indian J Novel Drug Delivery 2011;3:17-23.
23. Punitha K, Khadhir S, Ravichandiran V, Umadevi SK, Vaijayanthi V, Padmapriya S, et al. Intragastric floating drug delivery system of ranitidine hydrochloride: formulation and evaluation. Int J Pharm Pharm Sci 2010;2:105-8.
24. Yadava N, Mohiteb DD, Pawarb KR, Pawarb UR, Bhiseb SB, Sandeb TA. Synthesis and characterization of sustained release atenolol microspheres by solvent evaporation technique. J Pharm Sci Tech 2011;3:559-62.
25. Patil HS, Patil MP, Tekade BW, Thakare VM, Patil VR. Formulation and In-Vitro evaluation of floating microspheres of acyclovir. Arch Pharm Sci Res 2009;1:194-8.
26. Nepal PR, Chun MK, Choi HK. Preparation of floating microspheres for fish farming. Int J Pharm 2007;341:85-90.
27. Mateovic T, Kriznar B, Bogataj M, Marhar A. The influence of stirring rate on biopharmaceutical properties of Eudragit RS100 microspheres. J Microencapsulation 2002;19:29-36.
28. Mazumder B, Sarkar MK, Dey S, Roy N. Effect of formulation and process variables on the characteristics of microspheres of anti-viral drug (Stavudine) prepared by oil-in-oil solvent evaporation technique. Int J Pharm Pharm Sci 2010;2:52-9.
29. Nath B, Nath LK, Mazumder B, Kumar P, Sharma N, Sahu BP. Preparation and characterization of salbutamol sulphate loaded ethyl cellulose microspheres using water-in-oil-oil emulsion technique. Iran J Pharm Res 2010;9:97-105.
30. Khidr SH, Niazy EM, El-Sayed YM. Preparation and in-vitro evaluation of sustained release metochlopramide hydrochloride microspheres. J Microencapsul 1995;12:651-60.
31. Al-Helw AA, Al-Angary AA, Mahrrous GM, Al-Dardari MM. Preparation and evaluation of sustained release cross-linked chitosan microspheres. J Microencapsul 1998;15:373-82.
32. Mazumder B, Bhattacharya S, Mohanta B, Dey S, Maity A. Preparation and in-vitro evaluation of chlorpheniramine maleate loaded microspheres. Int J PharmTech Res 2009;1:905-13.
33. Jain SK, Rai G, Saraf DK, Agrawal GP. Albendazole microspheres for colonic delivery. ParmTech 2004;28:66-71.
34. Lin SY, Tzan YL, Weng CN, Lee CJ. Preparation of enteric coated microspheres of mycoplasma hyopnumoniae vaccine with cellulose acetate phthalate: 1. formulation condition and micrometric properties. J Microencapsul 1991;8:317-25.
35. Sato Y, Kawashima Y, Takeuchi H, Yamamoto H. Physicochmical properties to determine the buoyancy of hollow microspheres (Microballon) prepared by the emulsion solvent diffusion method. Eur J Pharm Biopharm 2003;55:297-304.
36. Lewis L, Boni R, Adeyeye CM. Effect of emulsifier blend on the characteristics of sustained release diclofenac microspheres. J Microencapsul 1998;15:283-98.
37. Ofokansi KC, Adikwu MU. Formulation and evaluation of microspheres based on gelatin-mucin admixtures for the rectal delivery of cefuroxime sodium. Trop J Pharm Res 2007;6:825-32.