Gastroretentive drug delivery system of ranitidine hydrochloride: Formulation and in vitro evaluation
- 3.6k Downloads
The purpose of this research was to prepare a gastroretentive drug delivery system of ranitidine hydrochloride. Guar gum, xanthan gum, and hydroxypropyl methylcellulose were evaluated for gel-forming properties. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of citric acid and stearic acid on drug release profile and floating properties were investigated. The addition of stearic acid reduces the drug dissolution due to its hydrophobic nature. A 32 full factorial design was applied to systemically optimize the drug release profile. The amounts of citric acid anhydrous (X1) and stearic acid (X2) were selected as independent variables. The times required for 50% (t50) and 80% drug dissolution (t80), and the similarity factor f2 were selected as dependent variables. The results of the full factorial design indicated that a low amount of citric acid and a high amount of stearic acid favors sustained release of ranitidine hydrochloride from a gastroretentive formulation. A theoretical dissolution profile was generated using pharmacokinetic parameters of ranitidine hydrochloride. The similarity factor f2 was applied between the factorial design batches and the theoretical dissolution profile. No significant difference was observed between the desired release profile and batches F2, F3, F6, and F9. Batch F9 showed the highest f2 (f2=75) among all the batches, and this similarity is also reflected in t50 (∼214 minutes) and t80 (∼537 minutes) values. These studies indicate that the proper balance between a release rate enhancer and a release rate retardant can produce a drug dissolution profile similar to a theoretical dissolution profile.
Keywordsranitidine hydrochloride gastroretentive floating drug delivery sustained release
Unable to display preview. Download preview PDF.
- 1.Histamine H2 antagonists. In: Drug Facts and Comparisons. 16th ed. St Louis, MO: Wolters Kluwer Co; 1996:1862–1876.Google Scholar
- 2.Somade S, Singh K. Comparative evaluation of wet granulation and direct compression methods for preparation of controlled release Ranitidine HCL tablets. Indian J Pharm Sci. 2002;64:285.Google Scholar
- 6.Coffin M, Parr A. Ranitidine solid dosage form. US Patent 5 407 687. April 18, 1995.Google Scholar
- 8.Chawla G, Bansal A. A means to address regional variability in intestinal drug absorption. Pharm Tech. 2003;27:50–68.Google Scholar
- 17.Peppas NA. Analysis of Fickian and non-Fickian drug release from polymers. Pharm Acta Helv. 1985;60:110–111.Google Scholar
- 19.Langenbucher F. Linearization of dissolution rate curves by the Weibull distribution. J Pharm Pharmacol. 1988;24:979–981.Google Scholar
- 20.Goldsmith JA, Randall N, Ross SD. On methods of expressing dissolution rate data. J Pharm Pharmacol. 1978;30:347–349.Google Scholar
- 21.Romero P, Costa JB, Chulia D. Statistical optimization of a controlled release formulation obtained by a double compression process: application of a Hadamard matrix and a factorial design. In: Wells JI, Rubinstein MH, Horwood E, eds. Pharmaceutical Technology, Controlled Drug Release. Vol 2. New York, NY: Ellis Harwood; 1991:44–58.Google Scholar
- 26.Guidance for Industry SUPAC-MR. Modified Release Solid Oral Dosage Forms Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation. Available at: http://www.fda.gov/cder/guidance/index.htm.Google Scholar
- 27.Moore J, Flanner H. Mathematical comparison of dissolution profiles. Pharm Tech. 1996;20:64–74.Google Scholar