AAPS PharmSciTech

, Volume 8, Issue 2, pp E25–E31 | Cite as

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

  • Dasharath M. Patel
  • Natavarlal M. Patel
  • Viral F. Patel
  • Darshini A. Bhatt


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 (X 1) and ethyl cellulose (X 2) 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.


Multiunit lipid granules Gelucire ranitidine hydrochloride floating 


  1. 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.CrossRefGoogle Scholar
  2. 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.CrossRefGoogle Scholar
  3. 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.CrossRefGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefGoogle Scholar
  7. 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.Google Scholar
  8. 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.CrossRefGoogle Scholar
  9. 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.Google Scholar
  10. 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.CrossRefGoogle Scholar
  11. 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.CrossRefGoogle Scholar
  12. 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.CrossRefGoogle Scholar
  13. 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.CrossRefGoogle Scholar
  14. 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.CrossRefGoogle Scholar
  15. 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.CrossRefGoogle Scholar
  16. 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.CrossRefGoogle Scholar
  17. 17.
    Sheu MT, Hsia AHO. Polyglycolized saturated glycerides as carrier and enhancer for drug penetration.Chin Pharm J. 2001;53: 107–111.Google Scholar
  18. 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.CrossRefGoogle Scholar
  19. 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.Google Scholar
  20. 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.CrossRefGoogle Scholar
  21. 21.
    Flynn M. Histamine H2 antagonists. In: Hagemann RC, Threlkeld DS, eds.Drug Facts and Comparisons. 50th ed. St Louis, MO: Wolters Kluwer Co; 1996:1862–1876.Google Scholar
  22. 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.Google Scholar
  23. 23.
    Lauritsen K. Clinical pharmacokinetics of drugs used in the treatment of gastro intestinal diseasesClin Pharmacokinet. 1990;19:11–31, 94–125.CrossRefGoogle Scholar
  24. 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.CrossRefGoogle Scholar
  25. 25.
    Basit A, Lacey L. Colonic metabolism of ranitidine: implications for its delivery and absorption.Int J Pharm. 2001;227:157–165.CrossRefGoogle Scholar
  26. 26.
    Coffin M, Parr A, inventors. Glaxo Inc. Ranitidine solid dosage form. US patent 5 407 687. April 18, 1995.Google Scholar
  27. 27.
    Mendenhall W, Sincich T, eds. Multiple regression. In:A Second Course in Business Statistics, Regression Analysis. 3rd ed. San Francisco, CA: Dellen Publishing Co; 1989:141–226.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2007

Authors and Affiliations

  • Dasharath M. Patel
    • 1
  • Natavarlal M. Patel
    • 1
  • Viral F. Patel
    • 1
  • Darshini A. Bhatt
    • 1
  1. 1.Dept of PharmaceuticsShri B. M. Shah College of Pharmaceutical Education & ResearchModasaIndia

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