Critical points in ethylcellulose matrices: Influence of the polymer, drug and filler properties

Percolation theory has been applied to study the drug release behaviour in multicomponent inert matrices containing ethylcellulose as a matrix forming polymer. Global influence of major formulation factors such as polymer viscosity, polymer particle size, drug and filler solubility and porosity of the tablets in drug release kinetics has been studied for the first time. Batches containing three viscosity grades of Ethocel™, microcrystalline cellulose (MCC) and lactose as fillers, a lubricant and flow aid mixture and three drugs with different solubility have been manufactured. For some batches, compression pressure was varied in order to obtain matrices with five levels of initial porosity. The behaviour of inert matrices was explained based on the percolation ranges of the main components of the formulation. The effect of the porosity percolation threshold was observed and the existence of a tricoherent drug-polymer-filler system is hypothesized.

[1]  S. Redner,et al.  Introduction To Percolation Theory , 2018 .

[2]  I. Caraballo.  Factors affecting drug release from hydroxypropyl methylcellulose matrix systems in the light of classical and percolation theories , 2010, Expert opinion on drug delivery.

[3]  C. Ferrero,et al.  Graft tapioca starch copolymers as novel excipients for controlled-release matrix tablets , 2010 .

[4]  I. Caraballo,et al.  Estimation of the percolation thresholds in acyclovir hydrophilic matrix tablets. , 2006, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[5]  A. Rabasco,et al.  Estimation of the percolation thresholds in dextromethorphan hydrobromide matrices. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[6]  C. Cavallari,et al.  Percolation thresholds in ultrasound compacted tablets. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[7]  J. Álvarez-Fuentes,et al.  Design of controlled release inert matrices of naltrexone hydrochloride based on percolation concepts. , 1999, International journal of pharmaceutics.

[8]  A. Rabasco,et al.  Influence of two different types of excipient on drug percolation threshold , 1998 .

[9]  J. Álvarez-Fuentes,et al.  Study of morphine hydrochloride percolation threshold in Eudragit® RS–PM matrices , 1998 .

[10]  S. Neau,et al.  Sustained release theophylline tablets by direct compression: Part 1: formulation and in vitro testing , 1998 .

[11]  Isidore Caraballo,et al.  The Role of the Drug/Excipient Particle Size Ratio in the Percolation Model for Tablets , 1998, Pharmaceutical Research.

[12]  Antonio M. Rabasco,et al.  Relationship Between Drug Percolation Threshold and Particle Size in Matrix Tablets , 1996, Pharmaceutical Research.

[13]  S. Neau,et al.  Ethylcellulose matrix controlled release tablets of a water-soluble drug , 1995 .

[14]  S. Neau,et al.  Compressibility and compactibility properties of ethylcellulose , 1994 .

[15]  Antonio M. Rabasco,et al.  Percolation theory : application to the study of the release behaviour from inert matrix systems , 1993 .

[16]  Hans Leuenberger,et al.  Matrix type controlled release systems II. Percolation effects in non-swellable matrices , 1993 .

[17]  H. Leuenberger,et al.  Formation of a tablet: a site and bond percolation phenomenon. , 1992, Journal of pharmaceutical sciences.

[18]  H. Leuenberger,et al.  Percolation Theory and Compactibility of Binary Powder Systems , 1990, Pharmaceutical Research.

[19]  N. Peppas,et al.  A simple equation for the description of solute release. III. Coupling of diffusion and relaxation , 1989 .

[20]  H. Leuenberger,et al.  The relationship between solid fraction and mechanical properties of compacts — the percolation theory model approach , 1988 .

[21]  H. Leuenberger,et al.  Percolation theory — a novel approach to solid dosage form design , 1987 .

[22]  Nicholas A. Peppas,et al.  A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs , 1987 .

[23]  N. Peppas,et al.  Mechanisms of solute release from porous hydrophilic polymers , 1983 .

[24]  T. Higuchi.  MECHANISM OF SUSTAINED-ACTION MEDICATION. THEORETICAL ANALYSIS OF RATE OF RELEASE OF SOLID DRUGS DISPERSED IN SOLID MATRICES. , 1963, Journal of pharmaceutical sciences.

[25]  Shayne C. Gad,et al.  Pharmaceutical manufacturing handbook : production and processes , 2008 .

[26]  J. Bonny,et al.  Matrix type controlled release systems: I. Effect of percolation on drug dissolution kinetics. , 1991, Pharmaceutica acta Helvetiae.