Effect of Drug Loading and Plasticizer on Drug Release from Polylactic Acid Film
Keywords:
polylactic acid, drug loading, plasticizer, drug releaseAbstract
The objective of this study was to evaluate the effect of drug loading and plasticizer level on the release kinetic from films composed of polylactic acid (PLA). First, the polymeric film of polylactic acid of 50 % low and 50% high molecular weights with different drug loadings (20, 25 and 30%) was prepared without the plasticizer Dibutyl sebacate (DBS) to evaluate the drug (pentoxifylline) release from the polymeric matrix. Secondly, the plasticizer (DBS) with different levels (10, 20 and 30 %) was added to the formulation and the drug release from the polymeric film was evaluated. Differential Scanning Calorimetry was used to characterize and study thermal behavior of the film and the drug. Gel Permeation Chromatography GPC was used to characterize the molecular weight of the polylactic acid. Scanning Electron Microscopy was used to characterize the film surface at different drug loadings. X-ray powder diffraction was used to measure crystals peaks of the drug and the polylactic acid. The effect of plasticizer on the drug release rate has a different effect based on the drug loading levels, at low drug loading level (10 and 20%), as plasticizer level increases the drug release rate , while at high drug loading (60% ) the drug release rate decreases as the plasticizer level increases.
References
Lee, V.H.L. and J.R. Robinson, Controlled drug delivery : fundamentals and applications. 2nd ed. Drugs and the pharmaceutical sciences. v. 29. 1987, New York: Dekker. xix, 716 p.
Aulton, M.E., Aulton's pharmaceutics : the design and manufacture of medicines. 3rd ed. 2007, Edinburgh ; New York: Churchill Livingstone. x, 717 p.
Bendix, D., Chemical synthesis of polylactide and its copolymers for medical applications. Polymer Degradation and Stability
Biodegradable Polymers and Macromolecules, 1998. 59(1-3): p. 129-135.
Ranade, V.V., Drug Delivery Systems: 3A. Role of Polymers in Drug Delivery. The Journal of Clinical Pharmacology, 1990. 30(1): p. 10-23.
Mitragotri, S., P.A. Burke, and R. Langer, Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nature Reviews Drug Discovery, 2014. 13(9): p. 655-672.
Frinking, P.J., et al., Effect of ultrasound on the release of micro-encapsulated drugs. Ultrasonics, 1998. 36(1-5): p. 709-12.
Langer, R., New methods of drug delivery. Science, 1990. 249(4976): p. 1527-1533.
Agnihotri, S.M. and P.R. Vavia, Drug loaded poly[Lac(Glc-Leu)] microparticles: Formulation and release characteristics. Colloids and Surfaces B: Biointerfaces, 2009. 74(1): p. 336-339.
Brittain, H.G. and K. Florey, Analytical profiles of drug substances and excipients. Vol. 25. 1992, San Diego ; Toronto: Academic Press. v.
Reynolds, J.E.F., et al., Martindale : the extra pharmacopoeia. 29th ed. 1989, London: Pharmaceutical Press. xxx, 1896.
Targhi, M.S., preparatiopn and evaluation of sustained release. these of Ph.D, 1990.
R. K. KULKARNI, E.G.M., A. F. HEGYELI, and FRED and R.K.K.K.C.P.C.N.F. Leonard, Biodegradable Poly(1actic acid) Polymers. J. BTOMEI). MATER. RES., 1971. 5(3): p. 169-181.
Yu, L., Amorphous pharmaceutical solids: preparation, characterization and stabilization. Advanced Drug Delivery Reviews Characterization of the Solid State, 2001. 48(1): p. 27-42.
Cheng, W.-T., S.-Y. Lin, and S.-L. Wang, Differential Scanning Calorimetry with Curve-Fitting Program Used to Quantitatively Analyze the Polymorphic Transformation of Famotidine in the Compressed Compact. Drug Development and Industrial Pharmacy, 2008. 34(12): p. 1368-1375.
Johari, G.P., et al., Characterizing amorphous and microcrystalline solids by calorimetry. Journal of Non-Crystalline Solids, 1990. 116(2-3): p. 282-285.
Omelczuk, M. and J. McGinity, The Influence of Polymer Glass Transition Temperature and Molecular Weight on Drug Release from Tablets Containing Poly(DL-lactic Acid). Pharmaceutical Research, 1992. 9(1): p. 26-32.
Raghavan, D., et al., Mapping Polymer Heterogeneity Using Atomic Force Microscopy Phase Imaging and Nanoscale Indentation. Macromolecules, 2000. 33(7): p. 2573-2583.
Magonov, S.N., V. Elings, and M.-H. Whangbo, Phase imaging and stiffness in tapping-mode atomic force microscopy. Surface Science, 1997. 375(2-3): p. L385-L391.
Zelko, R., et al., Effect of plasticizer on the dynamic surface tension and the free volume of Eudragit systems. International Journal of Pharmaceutics, 2002. 244(1-2): p. 81-86.
Saettone, M.F., et al., Effect of different polymer-plasticizer combinations on 'in vitro' release of theophylline from coated pellets. International Journal of Pharmaceutics, 1995. 126(1-2): p. 83-88.
Choi, K.-m., et al., Plasticization of poly(lactic acid) (PLA) through chemical grafting of poly(ethylene glycol) (PEG) via in situ reactive blending. European Polymer Journal, 2013. 49(8): p. 2356-2364.
Piorkowska, E., et al., Plasticization of semicrystalline poly(l-lactide) with poly(propylene glycol). Polymer, 2006. 47(20): p. 7178-7188.
Von Recum, H., et al., Degradation of polydispersed poly(L-lactic acid) to modulate lactic acid release. Biomaterials, 1995. 16(6): p. 441-447.
Milner, S.T., T.A. Witten, and M.E. Cates, Effects of polydispersity in the end-grafted polymer brush. Macromolecules, 1989. 22(2): p. 853-861.
Tongwen, X. and H. Binglin, Mechanism of sustained drug release in diffusion-controlled polymer matrix-application of percolation theory. International Journal of Pharmaceutics, 1998. 170(2): p. 139-149.
Miyajima, M., et al., Effect of polymer/basic drug interactions on the two-stage diffusion-controlled release from a poly(-lactic acid) matrix. Journal of Controlled Release, 1999. 61(3): p. 295-304.
Chieng, B.W., et al., Plasticized poly(lactic acid) with low molecular weight poly(ethylene glycol): Mechanical, thermal, and morphology properties. Journal of Applied Polymer Science, 2013. 130(6): p. 4576-4580.
Korner, A., et al., Molecular Information on the Dissolution of Polydisperse Polymers: Mixtures of Long and Short Poly(ethylene oxide). The Journal of Physical Chemistry B, 2005. 109(23): p. 11530-11537.
Soares, J.o.S. and P. Zunino, A mixture model for water uptake, degradation, erosion and drug release from polydisperse polymeric networks. Biomaterials, 2010. 31(11): p. 3032-3042.
Hassouna, F., et al., New approach on the development of plasticized polylactide (PLA): Grafting of poly(ethylene glycol) (PEG) via reactive extrusion. European Polymer Journal, 2011. 47(11): p. 2134-2144.
von Burkersroda, F., R. Gref, and A. Gopferich, Erosion of biodegradable block copolymers made of poly(d,l-lactic acid) and poly(ethylene glycol). Biomaterials, 1997. 18(24): p. 1599-1607.
Wu, C. and J.W. McGinity, Non-traditional plasticization of polymeric films. International Journal of Pharmaceutics, 1999. 177(1): p. 15-27.
Ugur, S., A. Dinc, and Y. Kislak, Effect of molecular weight on the dissolution properties of polystyrene latex films. Journal of Polymer Research, 2012. 19(9): p. 1-10.
Raghavan, S.L., et al., Crystallization of hydrocortisone acetate: influence of polymers. International Journal of Pharmaceutics, 2001. 212(2): p. 213-221.
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Copyright (c) 2019 Mohamed Mokhtar، Abdurrahim A. Elouzi، Ebtisam Benomran، Ebtesam Beshana
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