Effect of drug solubility, polymer, and filler on drug release from modified-release matrix tablets in hydroethanolic...

This study aimed to develop strategies to prevent accelerated drug release (alcohol-induced dose dumping) from modified-release matrix tablets in hydroethanolic media. Drugs with different solubility profiles (theophylline, propranolol HCl, paracetamol, and carbamazepine) were formulated with water-soluble or water-insoluble matrix formers, with optional addition of soluble or insoluble fillers. Drug release, medium uptake, and leaching were evaluated in 0.1 N HCl containing 0, 20, or 40% (v/v) ethanol. No release acceleration was observed for theophylline and propranolol HCl, which showed low solubility ratios between hydroethanolic and aqueous media (approximately 2). In contrast, paracetamol and carbamazepine (solubility ratio approximately 20) required formulation adjustments. For paracetamol, comparable release profiles across media were achieved using matrix formers with low medium uptake (e.g., Klucel® MXF or Kollidon® SR) or by incorporating a soluble filler such as lactose. For carbamazepine, the increased solubility in hydroethanolic media shifted the release mechanism from erosion-dominated to diffusion-dominated; similar release profiles were only obtained with hydrophilic polymers exhibiting relatively high erosion rates.