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AAPS PharmSciTech. 2005 December; 6(4): E553–E564.
Published online 2005 October 31. doi:  10.1208/pt060470
PMCID: PMC2750603

A model-dependent approach to correlate accelerated with real-time release from biodegradable microspheres

Abstract

The purpose of this study was to determine the feasibility of applying accelerated in vitro release testing to correlate or predict long-term in vitro release of leuprolide poly(lactideco-glycolide) microspheres. Peptide release was studied using a dialysis technique at 37°C and at elevated temperatures (50°C–60°C) in 0.1 M phosphate buffered saline (PBS) pH 7.4 and 0.1 M acetate buffer pH 4.0. The data were analyzed using a modification, of the Weibull equation. Peptide release was temperature dependent and complete within 30 days at 37°C and 3 to 5 days at the elevated temperatures. In vitro release profiles at the elevated temperatures correlated well with release at 37°C. The shapes of the release profiles at all temperatures were similar. Using the modified Weibull equation, an increase in temperature was characterized by an increase in the model parameter, α, a scaling factor for the apparent rate constant. Complete release at 37°C was shortened from ~30 days to 5 days at 50°C, 3.5 days at 55°C, 2.25 days at 60°C in PBS pH 7.4, and 3 days at 50°C in acetate buffer pH 4.0. Values for the model parameter β indicated that the shape of the release profiles at 55°C in PBS pH 7.4 (2.740) and 50°C in 0.1 M acetate buffer pH 4.0 (2.711) were similar to that at 37°C (2.577). The Ea for hydration and erosion were determined to be 42.3 and 19.4 kcal/mol, respectively. Polymer degradation was also temperature dependent and had an Ea of 31.6 kcal/mol. Short-term in vitro release studies offer the possibility of correlation with long-term release, thereby reducing the time and expense associated with longterm studies. Accelerated release methodology could be useful in the prediction of long-term release from extended release microsphere dosage forms and may serve as a quality control tool for the release of clinical or commercial batches.

Keywords: biodegradable microspheres, accelerated in vitro release, modified Weibull equation, sigmoidal triphasic release

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Ramstack M, Grandolfi G, Mannaert E, D’Hoore P, Lasser RA. Long-acting risperidone: prolonged-release injectable delivery of risperidone using Medisorb microsphere technology. Abstracts of the IXth International Congress on Schizophrenia Research. Schizophrenia Research. 2003;60:314–314. doi: 10.1016/S0920-9964(03)80260-8. [Cross Ref]
2. Kostanski JW, Thanoo BC, DeLuca PP. Preparation, characterization, and in vitro evaluation of 1- and 4-month controlled release orntide PLA and PLGA microspheres. Pharm Dev Technol. 2000;5:585–596. doi: 10.1081/PDT-100102043. [PubMed] [Cross Ref]
3. D’Souza SS, Selmin F, Murty SB, Qiu W, Thanoo BC, DeLuca PP. Assessment of fertility in male rats after extended chemical castration with a GnRH antagonist. AAPS PharmSci. 2004;6:E10–E10. doi: 10.1208/ps060110. [PubMed] [Cross Ref]
4. Woo BH, Na K-H, Dani BA, Jiang G, Thanoo BC, DeLuca PP. In vitro characterization and in vivo testosterone suppression of 6-month release poly(D,L-lactide) leuprolide microspheres. Pharm Res. 2002;19:546–550. doi: 10.1023/A:1015168301339. [PubMed] [Cross Ref]
5. Okada H, Doken Y, Ogawa Y, Toguchi H. Preparation of three-month injectable micro spheres of leuprorelin acetate using biodegradable polymers. Pharm, Res. 1994;11:1143–1147. doi: 10.1023/A:1018936815654. [PubMed] [Cross Ref]
6. Kane JM, Eerdekens M, Lindenmayer J-P, Keith SJ, Lesem M, Karcher K. Long-acting injectable Risperidone: efficacy and safety of the first long-acting atypical antipsychotic. Am J Psychiatry. 2003;160:1125–1132. doi: 10.1176/appi.ajp.160.6.1125. [PubMed] [Cross Ref]
7. Siewert M, Dressman J, Brown CK, Shah VP. FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms. AAPS PharmSciTech. 2003;4:E7–E7. doi: 10.1208/pt040107. [PMC free article] [PubMed] [Cross Ref]
8. Buchholz B. Accelerated degradation test on resorbable polymers. In: Plank H, Dauner M, Renardy M, editors. Degradation Phenomena of Polymeric Biomaterials. New York, NY: Springer-Verlag; 1992. pp. 67–76.
9. Makino K, Arakawa M, Kondo T. Preparation and in vitro degradation properties of polylactide microcapsules. Chem Pharm Bull (Tokyo) 1985;33:1195–1201. [PubMed]
10. Bergsma JE, Rozema FR, Bos RRM, Boering G, Joziasse CAP, Pennings AJ. In vitro predegradation at elevated temperatures of poly(lactide) J Mater Sci Mater Med. 1995;6:642–646. doi: 10.1007/BF00123445. [Cross Ref]
11. Reed AM, Gilding DK. Biodegradable polymers for use in surgery-poly(glycolic)/poly(lactic acid) homo and copolymers. 2. In vitro degradation. Polym. 1981;22:494–498. doi: 10.1016/0032-3861(81)90168-3. [Cross Ref]
12. Agarwal CM, Huang D, Schmitz JP, Athanasiou KA. Elevated temperature degradation of a 50[ratio]50 copolymer of PLA-PGA. Tissue Eng. 1997;3:345–352. doi: 10.1089/ten.1997.3.345. [Cross Ref]
13. Hakkarainen M, Albertsson A-C, Karlsson S. Weight losses and molecular weight changes correlated with the evolution of hydroxyacids in simulated in vivo degradation of homo- and copolymers of PLA and PGA. Polym Degrad Stabil. 1996;52:283–291. doi: 10.1016/0141-3910(96)00009-2. [Cross Ref]
14. Shameem M, Lee H, DeLuca PP. A short term (accelerated release) approach to evaluate peptide release from PLGA depot-formulations. AAPS PharmSci. 1999;1:E7–E7. doi: 10.1208/ps010307. [PMC free article] [PubMed] [Cross Ref]
15. D’Souza SS, DeLuca PP. Development of a dialysis in vitro release method for biodegradable microspheres. AAPS PharmSciTech. 2005;6:E42–E42. doi: 10.1208/pt060109. [PMC free article] [PubMed] [Cross Ref]
16. Rescigno A. Bioequivalence. Pharm Res. 1992;9:925–928. doi: 10.1023/A:1015809201503. [PubMed] [Cross Ref]
17. Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13:123–133. doi: 10.1016/S0928-0987(01)00095-1. [PubMed] [Cross Ref]
18. Polli JE, Rekhi GS, Augsburger LL, Shah VP. Methods to compare dissolution profiles and a rational for wide dissolution specifications for metoprolol tartrate tablets. J Pharm Sci. 1997;86:690–700. doi: 10.1021/js960473x. [PubMed] [Cross Ref]
19. Sathe PM, Tsong Y, Shah VP. In vitro dissolution profile comparison: statistics and analysis, model dependent approach. Pharm Res. 1996;13:1799–1803. doi: 10.1023/A:1016020822093. [PubMed] [Cross Ref]
20. Hixson AW, Crowell JH. Dependence of reaction velocity upon surface and agitation. Ind Eng Chem. 1931;23:923–931. doi: 10.1021/ie50260a018. [Cross Ref]
21. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25–35. doi: 10.1016/0378-5173(83)90064-9. [Cross Ref]
22. Katzhendler I, Hofman A, Goldberger A, Friedman M. Modeling of drug release from erodible tablets. J Pharm Sci. 1997;86:110–115. doi: 10.1021/js9600538. [PubMed] [Cross Ref]
23. Langebucher F. Linearization of dissolution rate curves by the Weibull distribution. J Pharm Pharmacol. 1972;27:979–981. [PubMed]
24. Kervinen L, Yliruusi J. Modelling S-shaped dissolution curves. Int J Pharm. 1993;92:115–122. doi: 10.1016/0378-5173(93)90270-P. [Cross Ref]

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists