Percolative transport and cluster diffusion near and below the percolation threshold of a porous polymeric matrix.
OBJECTIVE
The purpose of this research was to develop a quantitative mass transport model to describe the release of a drug from a porous inert matrix dosage form near and below the percolation threshold for the system.


METHODS
Cumulative release profiles were generated for a series of tablets composed of a binary mixture of varying amounts of non-conducting (poly(vinyl stearate)) and conducting (benzoic acid) components. The porous microstructure was analyzed using re-constructed three-dimensional images of leached microtomed tablet sections. Poly(vinyl stearate) was characterized for transport properties, molecular weight and thermal properties.


RESULTS
Based on percolation theory, the binary matrix was determined to have a percolation threshold of 0.09 +/- 0.02. Transport, which could not be explained by "classical" percolation theory or surface diffusion alone, was observed below the percolation threshold for the system.


CONCLUSIONS
A model describing transport near and below the percolation threshold in matrices composed of two phases, polymer and drug, was developed. The percolation model developed accounts for diffusion within the porous structure and through the inert, insoluble polymeric amorphous regions of the matrix. The low percolation threshold and subsequently high coordination was concluded to be due to the biphasic classical porous and nonclassical polymeric diffusional transport mechanisms associated with the system studied.
Hastedt
Jayne E
JE
Global Chem Pharm, ALZA Corporation, 1010 Joaquin Road, Mountain View, California 94043, USA. jhastedt@alzus.jnj.com
Wright
James L
JL
D000465:Algorithms; D019817:Benzoic Acid / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004058:Diffusion; D004304:Dosage Forms; D007202:Indicators and Reagents; D008567:Membranes, Artificial; D008956:Models, Chemical; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry*; D011145:Polyvinyls; D016062:Porosity; D013228:Stearates; D014783:Viscosity
D004304:Dosage Forms; D007202:Indicators and Reagents; D008567:Membranes, Artificial; D011108:Polymers; D011145:Polyvinyls; D013228:Stearates; C089542:poly(vinyl stearate); D019817:Benzoic Acid