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AAPS PharmSciTech. 2004 September; 5(3): 51–56.
Published online 2004 July 12. doi:  10.1208/pt050343
PMCID: PMC2750266

Preparation and evaluation of diltiazem hydrochloride-gelucire 43/01 floating granules prepared by melt granulation


The basic objective of this study was to explore the application of Gelucire 43/01 for the design of multi-unit floating systems of a highly water-soluble drug diltiazem HCl. Diltiazem HCl-Gelucire 43/01 granules were prepared by melt granulation technique. The granules were evaluated for in vitro and in vivo floating ability, surface topography, and in vitro drug release. Aging effect on storage was vvaluated using scanning electron microscopy, hot stage polarizing microscopy (HSPM), differential scanning calorimetry (DSC), and in vitro drug release. Granules were retained in stomach at least for 6 hours. Approximately 65% to 80% drug was released over 6 hours with initial fast release from the surface. Surface topography, HSPM, DSC study of the aged samples showed phase transformation of Gelucire. The phase transformation also caused significant increase in drug release. In conclusion, hydrophobic lipid, Gelucire 43/01, can be considered as an effective carrier for design of a multi-unit floating drug delivery system of highly water-soluble drugs such as diltiazem HCl.

Keywords: multi-unit lipid granules, floating, diltiazem hydrochloride, Gelucire, aging

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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. Ching HS, Park H, Kelly JR. Bioadhesive polymers as platform 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 the 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(4):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 Percirol 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(1):E1–E1. doi: 10.1208/pt020101. [PMC free article] [PubMed] [Cross Ref]
15. Kumar K, Shah MH, Ketkar AR, Kadam SS, Paradkar A. Effect of drug solubility and different excipients on floating behavior and release from glyceryl mono-oleate matrices.Int J Pharm. 2003. [PubMed]
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 glycerides bases. J Pharm Pharmacol. 1995;47:182–187. [PubMed]
20. Ketkar AR, Patil VB, Paradkar AR. Computer Aided Exploratory Data Analysis Model Fitting for Dissolution Kinetics: 4th International Symposium on Advances in Technology and Business Potential of New Drug Delivery System. Mumbai, India: Controlled Release Society Indian; 2002. pp. 62–62.
21. Parab PV, Oh CK, Ritschel WA. Sustained release from Precirol(glycerol palmito-stearate) matrix: effect of mannitol and hydroxypropyl methylcellulose on the release of theophylline. Drug Dev Ind Pharm. 1986;12:1309–1327. doi: 10.3109/03639048609065861. [Cross Ref]
22. Kaur R, Grant DJW, Eaves T. Comparision of polyethylene glycol and polyoxyethylene stearate as excipients for solid dispersion systems of griseofulvin and tolbutamide. II. Dissolution and solubility studies. J Pharm Sci. 1980;69:1321–1326. doi: 10.1002/jps.2600691122. [PubMed] [Cross Ref]
23. Savolainen M, Herder J, Khoo C, et al. Evaluation of polar lipid-hydrophilic polymer microparticles. Int J Pharm. 2003;262:47–62. doi: 10.1016/S0378-5173(03)00336-3. [PubMed] [Cross Ref]
24. Sutananta W, Craig DQM, Newton JM. The effects of ageing on the thermal behaviour and mechanical properties of pharmaceutical glycerides. Int J Pharm. 1994;111:51–62. doi: 10.1016/0378-5173(94)90401-4. [Cross Ref]
25. Sutananta W, Craig DQM, Newton JM. An investigation into the effect of preparation condition and storage on the rate of drug release from pharmaceutical glycerides bases. J Pharm Pharmacol. 1995;47:355–359. [PubMed]
26. Roussin P, Duddu S. Sustained release theophylline formulations, excipient systems and methods of production. US patent 6 171 615. January 9, 2001.

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