Modelling of drug release from coated granular pellets.

A mathematical model of drug release from coated pellets with a granular core has been developed. The model includes a dynamic description of all three main processes contributing to drug release from such a system, i.e. liquid inflow, drug dissolution, and liquid efflux caused by diffusion across the coating. The cumulative fraction of released drug has been shown to be determined by three rate constants, one for each process mentioned above, together with two dimensionless parameters. These parameters are related to the porosity of the pellet core and the solubility of the drug in the dissolution medium. The model has been validated by comparison with experimentally determined release profiles for pellets consisting of a granular core of microcrystalline cellulose containing dispersed salicylic acid, coated by a thin layer of ethyl cellulose.

[1]  M. Friedman,et al.  Enhancement of permeability of ethyl cellulose films for drug penetration , 1975, The Journal of pharmacy and pharmacology.

[2]  Y. Liao,et al.  Slow release from a coated sphere with slight deformations of coating film and drug matrix. , 1997, Journal of pharmaceutical sciences.

[3]  Senkevich Sb Industrial aspects of pharmaceutics. , 1948 .

[4]  L. J. Edwards The dissolution and diffusion of aspirin in aqueous media , 1951 .

[5]  Ian Gladwell,et al.  Algorithm 771: rksuite_90: Fortran 90 software for ordinary differential equation initial-value problems , 1997, TOMS.

[6]  G. Alderborn,et al.  Effect of intragranular porosity on compression behaviour of and drug release from reservoir pellets. , 2003, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[7]  C. Nyström,et al.  Physicochemical aspects of drug release: X. Investigation of the applicability of the cube root law for characterization of the dissolution rate of fine particulate materials , 1990 .

[8]  Fritz Ullmann,et al.  Ullmanns Encyklopädie der technischen Chemie , 1951 .

[9]  K. Sirkar,et al.  Mathematical model of a hybrid dispersed network-membrane-based controlled release system. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[10]  T. Phaechamud,et al.  Mechanistic modeling of drug release from chitosan coated tablets. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[11]  S. F. Lee,et al.  Slow release of urea through latex film , 1992 .

[12]  W. Nernst,et al.  Theorie der Reaktionsgeschwindigkeit in heterogenen Systemen , 1904 .

[13]  G. Ragnarsson,et al.  In vitro release characteristics of a membrane-coated pellet formulation — influence of drug solubility and particle size , 1992 .

[14]  E. Cox A method of assigning numerical and percentage values to the degree of roundness of sand grains , 1927 .

[15]  D. Crommelin,et al.  Hydrodynamic approach to dissolution rate , 1981, Pharmaceutisch weekblad.

[16]  A. W. Hixson,et al.  Dependence of Reaction Velocity upon surface and Agitation , 1931 .

[17]  Narisawa Shinji,et al.  Porosity-controlled ethylcellulose film coating. II. Spontaneous porous film formation in the spraying process and its solute permeability , 1994 .

[18]  B. Nilsson,et al.  Simulation and parametric study of a film-coated controlled-release pharmaceutical. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[19]  S. M. Lu,et al.  Mathematical analysis of drug release from a coated particle , 1993 .

[20]  K. Sirkar,et al.  A mathematical model of an aqueous-organic partition-based controlled release system using microporous membranes. , 1999, Journal of controlled release : official journal of the Controlled Release Society.

[21]  S. R. Cammarn,et al.  Predicting dissolution via hydrodynamics: salicylic acid tablets in flow through cell dissolution. , 2000, International journal of pharmaceutics.

[22]  F Theeuwes,et al.  Elementary osmotic pump. , 1975, Journal of pharmaceutical sciences.

[23]  A. Noyes,et al.  The rate of solution of solid substances in their own solutions , 1897 .

[24]  Erich Brunner,et al.  Reaktionsgeschwindigkeit in heterogenen Systemen , 1904 .

[25]  W. Higuchi Diffusional Models Useful in Biopharmaceutics: Drug Release Rate Processes , 1967 .

[26]  Y. Liao,et al.  Slow release from a coated sphere with a slightly deformed coating. , 1995, Journal of pharmaceutical sciences.

[27]  Wayne R. Cowell,et al.  Sources and development of mathematical software , 1984 .

[28]  S. M. Lu,et al.  Controlled release from a coated particle — Effects of initial conditions and methods of solution , 1995 .

[29]  I. Colombo,et al.  Modelling of drug-release from poly-disperse microencapsulated spherical particles , 2002, Journal of microencapsulation.

[30]  C. Nyström,et al.  Physicochemical aspects of drug release. XV. Investigation of diffusional transport in dissolution of suspended, sparingly soluble drugs , 1992 .

[31]  G. Golub,et al.  Scientific Computing and Differential Equations: An Introduction to Numerical Methods , 1991 .