Polymethylmethacrylate Coated Alginate Matrix Microcapsules for Controlled Release of Diclofenac Sodium
Tapas Pal, Shubhajit Paul, Biswanath Sa
DOI: 10.4236/pp.2011.22007   PDF    HTML     6,697 Downloads   15,242 Views   Citations


Polymethylmethacrylate (PMMA) coated microcapsules of diclofenac sodium (DFS) were prepared by a modified wa-ter-in-oil-in-water (W1/O/W2) emulsion solvent evaporation method using sodium alginate (SAL) as a matrix material in the internal aqueous phase (W1).Their performance with respect to controlled release of the drug in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were evaluated, and compared with non-matrix microcapsules prepared by the conventional W1/O/W2 emulsion solvent evaporation method. Scanning electron micrographs (SEM) revealed that all the microcapsules were discrete and spherical in shape; however, the surface porosity of the matrix microcap-sules appeared to be less than that of the non-matrix microcapsules. In case of non-matrix microcapsules, an increase in the volume of water in W1 phase resulted in decrease in the drug entrapment efficiency (DEE) along with increase in release of the drug in both SGF and SIF. While in case of matrix microcapsules increase in the amount of SAL in W1 phase and concentration of the coating polymer in organic phase led to increase in DEE of the matrix microcapsules and considerable decrease in the drug release in both SGF and SIF. No interaction between the drug and any of the polymers used to prepare microcapsules was evident from Fourier transform infra-red (FTIR) analysis. The matrix microcapsules prepared using higher concentration of SAL and PMMA released the drug following zero order or Case-II transport model. The matrix microcapsules appeared to be suitable for releasing lesser amounts of DFS in SGF and providing extended release in SIF.

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T. Pal, S. Paul and B. Sa, "Polymethylmethacrylate Coated Alginate Matrix Microcapsules for Controlled Release of Diclofenac Sodium," Pharmacology & Pharmacy, Vol. 2 No. 2, 2011, pp. 56-66. doi: 10.4236/pp.2011.22007.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. S. Satoskar, S. D. Bhandarkar and N. N. Rege, “Phar- macology and Pharmaceutics,” Popular Prakashan, Mum- bai, 2005.
[2] G. R. Hanson, “Analgesic, Antipyretic and Anti-inflam- matory Drug,” In: A. R. Gennaro, Ed., Remington: The Science and Practice of Pharmacy, Mack Publishing Company, Pennsylvania, p. 1211.
[3] P. B. Deasy, “Microencapsulation and Related Drug Pro- cesses,” Marcel Dekker Inc., New York, 1984, pp. 9-10.
[4] P. G. Welling and M. R. Dobrinska, “Dosing Consideration and Bioavailability Assessment of Controlled Drug Delivery Systems,” In: J. R. Robinsons and V. H. L. Lee, Eds., Controlled Drug Delivery, Fundamentals and Applications, Marcel Decker Inc., New York, 1987, p. 255.
[5] N. Follonier and E. Doelkar, “Biopharmaceutical Comparison of Oral Multiple-unit and Single-unit Sustained Release Dosage Forms,” STP Pharma Sciences, Vol. 2, 1992, pp. 141-158.
[6] S. S. Davis, J. G. Hardy, M. J. Taylor, D. R. Whalley and C. G. Wilson, “A Comparative Study of the Gastrointestinal Transit of a Pellet and Tablet Formulation,” International Journal of Pharmaceutics, Vol. 21, No. 2, 1984, pp. 167-177. doi:10.1016/0378-5173(84)90091-7
[7] N. K. Varde and D. W. Pack, “Microspheres for Controlled Release Drug Delivery,” Expert Opinion on Biological Therapy, Vol. 4, No. 1, 2004, pp. 35-51. doi:10.1517/14712598.4.1.35
[8] R. Alex and R. Bodmeier, “Encapsulation of Water-soluble Drugs by a Modified Solvent Evaporation Method. I. Effect of Process and Formulation Variables on Drug Entrapment,” Journal of Microencapsulation, Vol. 7, No. 3, 1990, pp. 347-355. doi:10.3109/02652049009021845
[9] T. K. Mandal, M. Shekleton, E. Onyebueke, L. Washington and T. Penson, “Effect of Formulation and Processing Factors on the Characteristics of Biodegradable Microcapsules of Zidovudine,” Journal of Microencapsulation, Vol. 13, No. 5, 1996, pp. 545-557. doi:10.3109/02652049609026040
[10] R. H. Parikh, J. R. Parikh, R. R. Dubey, H. N. Soni and K. N. Kapadia, “Poly(D,L-Lactide-Co-Glycolide) Microspheres Containing 5-Fluorouracil: Optimization of Process Parameters,” AAPS PharmSciTech, Vol. 4. No. 2, 2003, pp. 1-8.
[11] P. Sipos, I. Csóka, S. Sr?i?, K. Pintye-Hódi and I. Er?s, “Influence of Preparation Conditions on the Properties of Eudragit Microspheres Produced by a Double Emulsion Method,” Drug Development Research, Vol. 64, No. 1, 2005, pp. 41-54. doi:10.1002/ddr.10425
[12] S. Gibaud, A. Gaia and A. Astier, “Slow-release Melarsoprol Microparticles,” International Journal of Pharmaceutics, Vol. 243, 2002, pp. 161-166. doi:10.1016/S0378-5173(02)00278-8
[13] X. Q. Chen, Y. Y. Yang, L. Wang and T. S. Chung, “Effect of Inner Water Volume on the Peculiar Surface Morphology of Microspheres Fabricated by Double Emulsion Technique,” Journal of Microencapsulation, Vol. 18, No. 5, 2001, pp. 637-649.
[14] J. Rojas, H. Pinto-Alphandary, E. Leo, S. Pecquet, P. Couvreur and E. Fattal, “Optimization of the Encapsulation and Release of β-lactoglobulin Entrapped Poly(DL- lactide-co-glycolide) Microspheres,” International Journal of Pharmaceutics, Vol. 183, 1999, pp. 67-71. doi:10.1016/S0378-5173(99)00046-0
[15] Y. Capan, B. H. Woo, S. Gebrekidan, S. Ahmed and P. P. DeLuca, “Influence of Formulation Parameters on the Characteristics of Poly(D,L-lactide-co-glycolide) Microspheres Containing Poly(L-lysine) Complexed Plasmid DNA,” Journal of Control Release, Vol. 60, 1999, pp. 279-286. doi:10.1016/S0168-3659(99)00076-0
[16] K. F. Pistel and T. Kissel, “Effects of Salt Addition on the Microencapsulation of Proteins Using a w/o/w Double Emulsion Technique,” Journal of Microencapsulation, Vol. 17, No. 4, 2000, pp. 467-483.
[17] K. J. Zhu, H. L. Jiang, X. Y. Du, J. Wang, W. X. Xu and S. F. Liu, “Preparation and Characterization of hCG- loaded Polylactide or Poly(lactide-co-glycolide) Microspheres Using a Modified Water-in-oil-in-water (w/o/w) Emulsion Solvent Evaporation Technique,” Journal of Microencapsulation, Vol. 18, No. 2, 2001, pp. 247-260.
[18] J. X. Zhang, D. Chen, S. J. Wang and K. J. Zhu, “Optimizing Double Emulsion Process to Decrease the Burst Release of Protein from Biodegradable Polymer Microspheres,” Journal of Microencapsulation, Vol. 22, No. 4, 2005, pp. 413-422. doi:10.1080/02652040500098994
[19] H. Y. Zhou, X. C. Guang, C. S. Liu, X. H. Meng, L. J. Yu, X. Y. Liu and W. Liu, “Chitosan/Cellulose Acetate Microspheres Preparation and Ranitidine Release In-vitro,” Pharmaceutical Development and Technology, Vol. 10, 2005, pp. 219-225.
[20] P. Sriamornsak, N. Thirawong and K. Korkerd, “Swelling, Erosion and Release Behavior of Alginate-based Matrix Tablets,” European Journal of Pharmaceutics and Biopharmaceutics, Vol. 66, 2007, pp. 435-450. doi:10.1016/j.ejpb.2006.12.003
[21] J. H. Cui, J. S. Goh, S. Y. Park, P. H. Kim and B. J. Le, “Preparation and Physical Characterization of Alginate Microparticles Using Air Atomization Method,” Drug Development and Industrial Pharmacy, Vol. 27, 2001, pp. 309-319. doi:10.1081/DDC-100103730
[22] A. Halder, S. Maiti and B. Sa, “Entrapment Efficiency and Release Characteristics of Polyethyleneimine-treated or Untreated Calcium Alginate Beads Loaded with Propranolol-resin Complex,” International Journal of Pharmaceutics, Vol. 302, 2005, pp. 84-94. doi:10.1016/j.ijpharm.2005.06.020
[23] A. Nokhodchi and A. Tailor, “In Situ Cross-linking of Sodium Alginate with Calcium and Aluminum Ions to Sustaine the Release of Theophylline from Polymeric Matrices. II,” Farmaco, Vol. 59, 2004, pp. 999-1004. doi:10.1016/j.farmac.2004.08.006
[24] S. Mandal, S. K. Basu and Biswanath Sa, “Sustained Release of a Water-Soluble Drug from Alginate Matrix Tablets Prepared by Wet Granulation Method,” AAPS PharmSciTech, Vol. 10, No. 4, 2009, pp. 1348-1356. doi:10.1208/s12249-009-9333-z
[25] M. Vallet-Regí, S. Granado, D. Arcos, M. Gordo, M. V. Caba?as, C. V. Ragel, A. J. Salinas, A. L. Doadrio and J. San Román, “Preparation, Characterization and ‘In Vitro’ Release of Ibuprofen from Al2O3/PLA/PMMA Composites,” Journal of Biomedical Materials Research, Vol. 39, 1998, pp. 423-428. doi:10.1002/(SICI)1097-4636(19980305)39:3<423::AID-JBM11>3.0.CO;2-B
[26] A. J. Domb, “Polymer Site - Specific Pharmacotherapy,” John Wiley and Sons, New York, 1994, pp. 221-242.
[27] E. L. Parrot, “Milling,” In: L. Lachman, H. A. Liberman and J. L. Kanig, Eds., The Theory and Practice of Industrial Pharmacy, Lea and Fabiger, Washington Square, Philadelphia, 1991, p. 28.
[28] D. V. Ramesh, “Comparison of Oil-in-oil, Water-in-oil-in-water and Melt Encapsulation Techniques for the Preparation of Controlled Release B12 Poly (?-cprolactone) Microparticles,” Trends in Biomaterials and Artificial Organs, Vol. 23, 2009, pp. 21-23.
[29] X. Q. Chen, Y. Y. Yang, L. Wang and T. S. Chung, “Effects of Inner Water Volume on the Peculiar Surface Morphology of Microspheres Fabricated by Double Emulsion Technique,” Journal of Microencapsulation, Vol. 18, No. 5, 2001, pp. 637-649.
[30] M. K. Lai and R. C. C. Tsiang, “Microencapsulation of Acetaminophen into Poly(L-lactide) by Three Different Emulsion Solvent-evaporation Methods,” Journal of Microencapsulation, Vol. 22, No. 3, 2005, pp. 261-274. doi:10.1080/02652040500100261
[31] M. K. Yeh, S. M. Tung, D. W. Lu and C. H. Chiang, “Formulation Factors for Preparing Ocular Biodegradable Delivery System of 5-fluorouracil Microparticles,” Journal of Microencapsulation, Vol. 18, No. 4, 2001, pp. 507-519.
[32] R. Dinarvand , S. H. Moghadam, A. Sheikhi and F. Atyabi, “Effect of Surfactant HLB and Different Formulation Variables on the Properties of Poly-D,L-lactide Microspheres of Naltrexone Prepared by Double Emulsion Technique,” Journal of Microencapsulation, Vol. 22, No. 2, 2005, pp. 139-151. doi:10.1080/02652040400026392
[33] S. Kiyoyama, K. Shiomori, Y. Kawano and Y. Hatate, “Preparation of Microcapsules and Control of Their Morphology,” Journal of Microencapsulation, Vol. 20, No. 4, 2003, pp. 497-508. doi:10.1080/0265204031000093096
[34] G. Crotts and T. G. Park, “Protein Delivery from Poly (lactic-co-glycolic acid) Biodegradable Microspheres: Release Kinetics and Stability Issues,” Journal of Microencapsulation, Vol. 15, No. 6, 1998, pp. 699-713. doi:10.3109/02652049809008253
[35] H. K. Sah, R. Toddywala and Y. W. Chien, “The Influence of Biodegradable Microcapsule Formulations on the Controlled Release of a Protein,” Journal of Control Release, Vol. 30, 1994, pp. 201-211. doi:10.1016/0168-3659(94)90026-4
[36] P. L. Ritger and N. A. Peppas, “A Simple Equation for Description of Solute Release II. Fickian and Anomalous Release from Swellable Devices,” Journal of Controlled Release, Vol. 5, No. 1, 1987, pp. 37-42. doi:10.1016/0168-3659(87)90035-6

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