EFFECT OF POLYMERIC EXCIPIENT MOLECULAR WEIGHT ON DRUG RELEASE PROFILES INVESTIGATED BY ONLINE MONITORED CONTROLLED RELEASE STUDIES

Year 2015, Volume: 33 Issue: 3, 407 - 416, 01.09.2015

Hatice İmran Güngördü Nil Erge Akkaya Ahmet Giz Huceste Çatalgil Giz

Abstract

Ascorbic acid loaded polyvinylpyrrolidone tablets are prepared and ascorbic acid release profiles are monitored by the automatic continuous online monitoring of polymerization (ACOMP) system. Three different molecular weights of polymers are used in tablets. Parallel experiments are performed using powder samples. Drug release from tablets is investigated as zeroth and halfth order processes for the dissolution step and a first order process for the diffusion step. Powder samples are investigated on the basis of a first order diffusion model. Kinetic rate constants for the dissolution and diffusion processes are calculated. Release profiles are found to depend strongly on the molecular weights of the polymers. Higher molecular weights are found to slow down both the dissolution and the diffusion processes. Diffusion constants are compared with independent viscosity measurements.

Keywords

Online monitoring, drug delivery systems, biomedical applications, dissolution, diffusion

References

• [1] Mallapragada, S.K, Peppas, N.A., “Crystal dissolution-controlled release systems: I. Physical characteristics and modeling analysis”, Control. Release. 45, 87-94, 1997.
• [2] Mallapragada, S.K, Peppas, N.A., Colombo, P., “Crystal dissolution-controlled release systems. II. Metronidazole release from semicrystalline poly (vinyl alcohol) systems”, J Biomed. Mat. Res. 36, 125-130, 1997.
• [3] Kurnik, R.T., Potts, R.O., “Modeling of diffusion and crystal dissolution in controlled release systems”, J. Control. Release. 45, 257-264, 1997.
• [4] Ramkissoon-Ganorkar, C., Liu, F., Baudys, M., Kim, S.W,.”Modulating insulin-release profile from pH/ thermosensitive polymeric beads through polymer molecular weight”. J. Control. Release. 59(3), 287-298, 1999.
• [5] Hong, S.I., Oh, S.Y., “Dissolution kinetics and physical characterization of three-layered tablet with poly (ethylene oxide) core matrix capped by Carbopol”, Int. J. Pharm., 356, 121-129, 2008.
• [6] Wu, N., Wang, S-L., Tan, D.C-W., Moochhala, S.M., Yang, Y-Y., “Mathematical modeling and in vitro study of controlled drug release via a highly swellable and dissolvable polymer matrix: polyethylene oxide with high molecular weights”. J. Control. Release.102, 569-581, 2005
• [7] Zelko, R., Suvegh, K., “Correlation between the release characteristics of theophylline and the free volume of polyvinylpyrrolidone”. European Journal of Pharmaceutical Sci. 24(4), 351-354, 2005.
• [8] Siepmann, F., Eckart, K., Maschke, A., Kolter, K., Siepmann, J., “Modeling drug release from PVAc/PVP matrix tablets”. J. Control. Release.141, 216-222, 2010.
• [9] Sullad, A.G., Manjeshwar, L.S., Aminabhavi, T.M., “Polymeric Blend Microspheres for Controlled Release of Theophylline”. J. Appl. Polym. Sci. 117, 1361-1370, 2010.
• [10] Kumar, J., Shakil, N.A., Singh, M.K., Pankaj, Singh, M.K Pandey, A., Pandey, R.P., “Development of controlled release formulations of azadirachtin-A employing poly (ethylene glycol) based amphiphilic copolymers”. J. Environmental Sci. and Health Part B. 45(4), 310-314, 2010.
• [11] Ekici, S., Saraydin, D., “Chitosan Interpenetrating polymeric network hydrogels for potential gastrointestinal drug release”. Polym. Int. 56, 1371-1377, 2007.
• [12] Wang, Q., Ellis, P.R., Ross-Murphy, S.B., “Dissolution kinetics of water-soluble polymers: The guar gum paradigm”. Carbohydrate Polymers, 74, 519-526, 2008.
• [13] Miyazaki, T., Yomota, C., Okada, S., “Development and release characterization of hyaluronan–doxycycline gels based on metal coordination”. J. Control. Release. 76, 337-347, 2001.
• [14] Pose-Vilarnovo, B., Rodriguez-Tenreiro, C., Dos Santos, J.F.R., Vazquez-Doval, J., Concheiro, A., Alvarez-Lorenzo, C., Torres-Labandeira, J.J., “Modulating drug release with cyclodextrins in hydroxypropyl methylcellulose gels and tablets”. J. Control. Release. 94, 351-363, 2004.
• [15] Schreiner, T., Schaefer, U.F., Loth, H., “Immediate Drug Release from Solid Oral Dosage forms”. J. Pharmaceutical Sci. 94, 120-133, 2005.
• [16] Peppas, N.A., “Analysis of Fickian and non-Fickian drug release from polymers”. Pharmaceutica Acta Helvetiae, 60, 110-111, 1985.
• [17] Peppas, N.A., Wu, J.C., Von Meerwall, E.D., “Mathematical-modeling and experimental characterization of polymer dissolution”. Macromolecules. 27, 5626-5638, 1994.
• [18] Rothstein, S.N., Federspiel, W.J., Little, S.R., 2009. A unified mathematical model for the prediction of controlled release from surface and bulk eroding polymer matrices. Biomaterials, 30, 1657-1664, 2008.
• [19] Frenning, G., Stromme, M., “Drug release modeled by dissolution, diffusion, and immobilization”. Int. J. Pharma. 250, 137-146, 2003.
• [20] Rothstein, S.N., Federspiel, W.J., Little, S.R., “A simple model framework for the prediction of controlled release from bulk eroding polymer matrices”. J. Mater. Chem. 18, 1873-1880, 2008.
• [21] Khan, M., A., Shefeeq, T., “Role of Mathematical Modeling in Controlled Drug Delivery”. J. Sci. Res., 1, 539- 550, 2009.
• [22] Costa, P., Lobo, J.M.S., “Modeling and comparison of dissolution profiles”, European J. Pharma. Sci. 13, 123-133, 2001.
• [23] Macheras, P., Dokoumetzidis, A., “On the Heterogeneity of Drug Dissolution and Release”, Pharmaceutical Research. 17, 108-112, 2000.
• [24] Soares, J.S., Zunino, P., “A mixture model for water uptake, degradation, erosion and drug release from polydisperse polymeric networks”, Biomaterials. 31, 3032-3042, 2010.
• [25] Marucci, M., Andersson. H., Hjärtstam, J., Stevenson, G., Baderstedt, J., Stading, M., Larsson, A., Von Corswant, C., “New insights on how to adjust the release profile from coated pellets by varying the molecular weight of ethyl cellulose in the coating film”, Int. J. Pharma. 458, 218-223, 2013.
• [26] Giz, A., Çatalgil-Giz, H., Alb, A., Brousseau, J-L., Reed, W.F., “Kinetics and Mechanisms of Acrylamide Polymerization from absolute online monitoring of Polymerization Reaction”, Macromolecules, 34, 1180-1191, 2001.
• [27] Catalgil-Giz, H., Giz, A., Alb, A., Reed, W.F., “Absolute online monitoring of acrylic acid polymerization and the effect of salt and pH on the reaction kinetics”, J. Appl. Polym. Sci. 91, 1352-1359, 2004.
• [28] Catalgil-Giz, H., Giz, A., Alb, A.M., Öncül-Koç, A., Reed, W.F., “Online monitoring of composition, sequence length, and molecular weight distributions during free radical copolymerization, and subsequent determination of reactivity ratios”, Macromolecules, 35(17), 6557-6571, 2002.
• [29] Paril, A., Alb, A.M., Giz, A.T., Çatalgil-Giz, H.. “Effect of medium pH on the reactivity ratios in acrylamide acrylic acid copolymerization”, J. Appl. Polym. Sci. 103(2), 968-974, 2007.
• [30] Sunbul, D., Paril, A., Alb, A.M., Catalgil-Giz, H., Giz A.T., “Monomer and radical reactivity ratios in 4-vinylbenzenesulfonic acid sodium salt–acrylamide copolymerization in 0.1M NaCl solution”, J. Appl. Polym. Sci. 120, 850-856, 2011.
• [31] Akyuz, A., Catalgil-Giz, H., Giz, A.T., “Kinetics of Ultrasonic Polymer Degradation: Comparison of Theoretical Models with On-Line Data”, Macromol. Chem. Phys. 209, 801-809, 2008.
• [32] Akyuz, A.O., Giz, A., Catalgil-Giz, H., “Investigation of Termination during Ultrasonic Depolymerization”, Macromol. Symp. 275-276, 112-119, 2008.
• [33] Akyuz, A., Catalgil-Giz, H., Giz, A., “Effect of Solvent Characteristics on the Ultrasonic Degradation of Poly (vinylpyrrolidone) Studied by On-line Monitoring”, Macromol. Chem. Phys. 210, 1331-1338, 2009.