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AAPS PharmSciTech. 2007 June; 8(2): E25–E31.
Published online 2007 April 13. doi:  10.1208/pt0802030
PMCID: PMC2750366

Floating granules of ranitidine hydrochloride-gelucire 43/01: Formulation optimization using factorial design


The purpose of this research was to develop and optimize a controlled-release multiunit floating system of a highly water soluble drug, ranitidine HCl, using Compritol, Gelucire 50/13, and Gelucire 43/01 as lipid carriers. Ranitidine HCl-lipid granules were prepared by the melt granulation technique and evaluated for in vitro floating and drug release. ethyl cellulose, methylcellulose, and hydroxypropyl methylcellulose were evaluated as release rate modifiers. A 32 full factorial design was used for optimization by taking the amounts of Gelucire 43/01 (X1) and ethyl cellulose (X2) as independent variables, and the percentage drug released in 1(Q1), 5(Q5), and 10 (Q10) hours as dependent variables. The results revealed that the moderate amount of Gelucire 43/01 and ethyl cellulose provides desired release of ranitidine hydrochloride from a floating system. Batch F4 was considered optimum since it contained less Gelucire and was more similar to the theoretically predicted dissolution profile (f2=62.43). The temperature sensitivity studies for the prepared formulations at 40°C/75% relative humidity for 3 months showed no significant change in in vitro drug release pattern. These studies indicate that the hydrophobic lipid Gelucire 43/01 can be considered an effective carrier for design of a multiunit floating drug delivery system for highly water soluble drugs such as ranitidine HCl.

Keywords: Multiunit lipid granules, Gelucire, ranitidine hydrochloride, floating

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Selected References

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1. Iannuccelli V, Coppi G, Bernabei MT, Cameroni R. Air compartment multiple-unit system for prolonged gastric residence, Part I: formulation study. Int J Pharm. 1998;174:47–54. doi: 10.1016/S0378-5173(98)00229-4. [Cross Ref]
2. Santus G, Lazzarini G, Bottoni G, et al. Anin vitro-in vivo investigation of oral bioadhesive controlled release furosemide formulations. Eur J Pharm Biopharm. 1997;44:39–52. doi: 10.1016/S0939-6411(97)00100-8. [Cross Ref]
3. Deshpande AA, Rhodes CT, Shah NH, Malick AW. Controlled-release drug delivery systems for prolonged gastric residence: an overview. Drug Dev Ind Pharm. 1996;22:531–539. doi: 10.3109/03639049609108355. [Cross Ref]
4. Deshpande AA, Shah NH, Rhodes CT, Malick W. Development of a novel controlled-release system for gastric retention. Pharm Res. 1997;14:815–819. doi: 10.1023/A:1012171010492. [PubMed] [Cross Ref]
5. Menon A, Ritschel WA, Sakr A. Development and evaluation of a monolithic floating dosage form for furosemide. J Pharm Sci. 1994;83:239–245. doi: 10.1002/jps.2600830225. [PubMed] [Cross Ref]
6. Whitehead L, Fell JT, Collett JH, Sharma HL, Smith AM. Floating dosage forms: an in vivo study demonstrating prolonged gastric retention. J Control Release. 1998;55:3–12. doi: 10.1016/S0168-3659(97)00266-6. [PubMed] [Cross Ref]
7. Park K, Park H. Enzyme digestible balloon hydrogel for long term oral drug delivery: synthesis and characterization. Int Symp Rel Bioact Mater. 1987;14:41–42.
8. Ch'Ng HS, Park H, Kelly P, Robinson JR. Bioadhesive polymers as platforms for oral controlled drug delivery, II: synthesis and evaluation of some swelling water-insoluble bioadhesive polymers. J Pharm Sci. 1985;74:399–405. doi: 10.1002/jps.2600740407. [PubMed] [Cross Ref]
9. Kaniwa N, Aoyagi N, Ogata H, Ejima A. Gastric emptying of enteric coated drug preparations, II: effect of size and density of enteric coated drug preparations and food on gastric emptying rates in humans. J Pharmacobiodyn. 1988;11:571–575. [PubMed]
10. Efentakis M, Koutlis A, Vlachou M. Development and evaluation of oral multiple-unit and single-unit hydrophilic controlled-release systems. AAPS PharmSciTech. 2000;1:E34–E34. doi: 10.1208/pt010434. [PMC free article] [PubMed] [Cross Ref]
11. Dennis AB, Farr SJ, Kellaway IW, Taylor G, Davidson R. In vivo evaluation of rapid release and sustained release Gelucire capsule formulations. Int J Pharm. 1990;65:85–100. doi: 10.1016/0378-5173(90)90013-T. [Cross Ref]
12. Remunan C, Bretal M, Nunez A, Bila Jato JL. Accelerated stability of sustained release tablet prepared with Gelucire. Int J Pharm. 1992;80:151–159. doi: 10.1016/0378-5173(92)90273-5. [Cross Ref]
13. Saraiya D, Bolton D. The use of Precirol to prepare sustained release tablets of theophylline and quinidine gluconate. Drug Dev Ind Pharm. 1990;16:1963–1969. doi: 10.3109/03639049009023634. [Cross Ref]
14. Li S, Lin S, Chien YW, Daggy BP, Mirchandani HL. Statistical optimization of gastric floating system for oral controlled delivery of calcium. AAPS PharmSciTech. 2001;2:E1–E1. doi: 10.1208/pt020101. [PMC free article] [PubMed] [Cross Ref]
15. Kumar MK, Shah MH, Ketkar A, Mahadik KR, Paradkar A. Effect of drug solubility and different excipients on floating behavior and release from glyceryl monooleate matrices. Int J Pharm. 2004;272:151–160. doi: 10.1016/j.ijpharm.2003.12.025. [PubMed] [Cross Ref]
16. Aïnaoui A, Vergnaud JM. Modelling the plasma drug level with oral controlled release forms with lipidic Gelucire. Int J Pharm. 1998;169:155–162. doi: 10.1016/S0378-5173(98)00105-7. [Cross Ref]
17. Sheu MT, Hsia AHO. Polyglycolized saturated glycerides as carrier and enhancer for drug penetration. Chin Pharm J. 2001;53:107–111.
18. Barker SA, Yap SP, Yuen KH, McCoy CP, Murphy JR, Craig DQM. An investigation into the structure and bioavailability of α-tocopherol dispersion in Gelucire 44/14. J Control Release. 2003;91:477–488. doi: 10.1016/S0168-3659(03)00261-X. [PubMed] [Cross Ref]
19. Sutananta W, Craig DQM, Newton JM. An evaluation of the mechanisms of drug release from glyceride bases. J Pharm Pharmacol. 1995;47:182–187. [PubMed]
20. 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:E43–E43. doi: 10.1208/pt050343. [PMC free article] [PubMed] [Cross Ref]
21. Flynn M. Histamine H2 antagonists. In: Hagemann RC, Threlkeld DS, editors. Drug Facts and Comparisons. 50th ed. St Louis, MO: Wolters Kluwer Co; 1996. pp. 1862–1876.
22. 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;64:285–285.
23. Lauritsen K. Clinical pharmacokinetics of drugs used in the treatment of gastro intestinal diseases. Clin Pharmacokinet. 1990;19(11–31):94–125. doi: 10.2165/00003088-199019020-00002. [PubMed] [Cross Ref]
24. Grant S. Ranitidine: an updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in peptic ulcer disease and other allied diseases. Drugs. 1989;37:801–870. doi: 10.2165/00003495-198937060-00003. [PubMed] [Cross Ref]
25. Basit A, Lacey L. Colonic metabolism of ranitidine: implications for its delivery and absorption. Int J Pharm. 2001;227:157–165. doi: 10.1016/S0378-5173(01)00794-3. [PubMed] [Cross Ref]
26. Coffin M, Parr A, inventors. Glaxo Inc. Ranitidine solid dosage form. US patent 5 407 687. April 18, 1995.
27. Mendenhall W, Sincich T, editors. Multiple regression. 3rd ed. San Francisco, CA: Dellen Publishing Co; 1989. pp. 141–226.

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