Effects of Drug Solubility, Drug Loading, and Polymer Molecular Weight on Drug Release from Polyox® Tablets

Abstract

This study investigated the effects of polymer molecular weight, drug solubility, addition of a water-soluble excipient, and drug loading on zero-order release kinetics and elucidated the release mechanism of a drug from directly compressed tablets. Directly compressed tablets consisting of polyethylene oxides (PEO) (MW - 0.9, 2.0 and 4.0 × 106) and drugs (solubility ranging from 290 to 25,000 mg/l) were formulated with or without a water-soluble excipient (lactose). For PEO tablets (MW = 0.9 × 106), drug release is primarily swelling/erosion controlled for drugs for which solubility is below 1%, resulting in zero-order release kinetics. For PEO tablets (MW = 4.0 × 106), drug release is controlled at a zero-order rate by the dissolution rate of the drug at high loading (39%). At low loading (20%), drug diffusion through the swollen gel layer becomes the governing release mechanism. For a highly water-soluble drug (e.g., diclofenac Na), drug diffusion is the controlling mechanism regardless of the molecular weight of the PEOs. Zero-order release kinetics can be achieved with PEO tablets (MW = 0.9 × 106) for drugs for which solubility is below 1%. PEO tablets (MW = 2.0 × 106) provided zero-order release for poorly water-soluble drugs (below 0.2%) at 39% drug loading. It is possible to attain zero-order release kinetics with PEO tablets (MW = 4.0 × 106) using a drug which has a solubility of less than 0.1%.