Search tips
Search criteria 


Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
AAPS PharmSciTech. 2000 December; 1(4): 26–34.
Published online 2000 July 20. doi:  10.1208/pt010429
PMCID: PMC2750453

A bioresorbable, polylactide reservoir for diffusional and osmotically controlled drug delivery


The purpose of this study was to design and characterize a zero-order bioresorbable reservoir delivery system (BRDS) for diffusional or osmotically controlled delivery of model drugs including macromolecules. The BRDS was manufactured by casting hollow cylindrical poly (lactic acid) (PLA): polyethylene glycol (PEG) membranes (10×1.6 mm) on a stainless steel mold. Physical properties of the PLA:PEG membranes were characterized by solid-state thermal analysis. After filling with drug (5 fluorouracil [5FU] or fluorescein isothiocyanate [FITC]-dextranmannitol, 5:95 wt/wt mixture) and sealing with viscous PLA solution, cumulative in vitro dissolution studies were performed and drug release monitored by ultraviolet (UV) or florescence spectroscopy. Statistical analysis was performed using Minitab® (Version 12). Differential scanning calorimetry thermograms of PLA:PEG membranes dried at 25°C lacked the crystallization exotherms, dual endothermal melting peaks. and endothermal glass transition observed in PLA membranes dried at −25°C. In vitro release studies demonstrated zero-order release of 5FU for up to 6 weeks from BRDS manufactured with 50% wt/wt PEG (drying temperature, 25°C). The release of FITC dextrans of molecular weights 4400, 42 000, 148 000, and 464 000 followed zero-order kinetics that were independent of the dextran molecular weight. When monitored under different concentrations of urea in the dissolution medium, the release rate of FITC dextran 42 000 showed a linear correlation with the calculated osmotic gradient (Δπ). PEG inclusion at 25°C enables manufacture of uniform, cylindrical PLA membranes of controlled permeability. The absence of molecular weight effects and a linear dependence of FITC-dextran release rate on Δπ confirm that the BRDS can be modified to release model macromolecules by an osmotically controlled mechanism.

Key Words: Zero-order, Reservoir, PLA, Osmotic Delivery, Thermal Analysis

Full Text

The Full Text of this article is available as a PDF (392K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Yang L, Fassihi R. Zero-order release kinetics of a selfcorrecting floatable asymmetric configuration drug delivery system. J Pharm Sci. 1996;85(2):170–173. doi: 10.1021/js950250r. [PubMed] [Cross Ref]
2. Theeuwes F, Swanson D, Wong P, et al. Elementary osmotic pump for indomethacin. J Phanm Sci. 1983;72(3):253–258. doi: 10.1002/jps.2600720313. [PubMed] [Cross Ref]
3. Kim CJ. Compressed donut-shaped tablets with zero-order release kinetics. Pharm Res. 1995;12(7):1045–48. doi: 10.1023/A:1016218716951. [PubMed] [Cross Ref]
4. Mishra DS, Yalkowsky SH. A flat circular hole device for zeroorder release of drugs: characterization of the moving dissolution boundary. Pharm Res. 1990;7(11):1195–97. doi: 10.1023/A:1015900913702. [PubMed] [Cross Ref]
5. Kun WY, Yalkowsky SH. Multiple-hole approach to zero-order release. J Pharm Sci. 1985;74(9):926–933. doi: 10.1002/jps.2600740904. [PubMed] [Cross Ref]
6. Hsieh DST, Rhine WD, Langer R. Zero-order controlled-release polymer matrices for micro and macromolecules. J Pharm Sci. 1983;72(1):17–22. doi: 10.1002/jps.2600720105. [PubMed] [Cross Ref]
7. Bayomi MA. Geometric approach for zero-orderrelease of drug: dispersed in an inert matrix. Pharm Res. 1994;11(6):914–916. doi: 10.1023/A:1018902513411. [PubMed] [Cross Ref]
8. Lee PI. Novel approach to zero-order drug delivery via immobilized nonuniform drug distribution in glassy hydrogels. J. Pharm Sci. 1984;73(10):1344–1347. doi: 10.1002/jps.2600731004. [PubMed] [Cross Ref]
9. Möckel JE, Lippold BC. Zero-order drug release from hydrocolloidmatrices. Pharm Res. 1993;10(7):1066–1070. doi: 10.1023/A:1018931210396. [PubMed] [Cross Ref]
10. Lindstedt B, Agnarsson G, Hjärtstam J. Osmotic pumping as a release mechanism for membrane-coated drug fomulations. Int J Pharm. 1989;564:261–268. doi: 10.1016/0378-5173(89)90023-9. [Cross Ref]
11. Lopaschuk GD, Tahiliani AG, McNeill JH. Continuous longterm insulin delivery in diabetic rats utilizing implated osmotic minipumps. J Pharmacol Methods. 1982;9:71–75. doi: 10.1016/0160-5402(83)90052-9. [PubMed] [Cross Ref]
12. Santus G, Baker RW. Osmotic drug delivery: a review of patnent literature. J Control Rel. 1995;35:1–21. doi: 10.1016/0168-3659(95)00013-X. [Cross Ref]
13. Theeuwes F. Elementary osmotic pump. J Pharm Sci. 1975;64(12):1987–1991. doi: 10.1002/jps.2600641218. [PubMed] [Cross Ref]
14. Agarwal RK. Development and Evaluation of Bioresorbable Membranes for the Controlled Release of Tetracycline HCl into Intracrevicular Fluic. Omaha, NE: University of Nebraska Medical Center; 1994.
15. Marcotte N, Polk A, Goosen MF. Kinetics of protein diffusion from a poly(D,L- lactide) reservoir system. J Pharm Sci. 1990;79(5):407–410. doi: 10.1002/jps.2600790509. [PubMed] [Cross Ref]
16. Sato S, Kim SW. Macromolecular diffusion through polymer membranes. Inter J Pharm. 1984;22:229–225. doi: 10.1016/0378-5173(84)90024-3. [Cross Ref]
17. Demirdere A, Kissel T, Siemann U, Sucker H. Permeability and release properties of bioresorbable polymers. Part I: Feasibility of reservoir systems. Eur J Biopharm. 1991;37(1):42–48.
18. Weast RC, Astle MJ.CRC Handbook of Chemistry and Physics. Boca Raton, FL: CRC Press, Inc.: 1981–1982.
19. Bershtein VA, Egorov VM. Differential Scanning Calorimetry of Polymers: Physics, Chemistry, Analysis, Technology. New York: Ellis Horword Ltd.; 1994.

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