Effects of drug solubility, drug loading, and polymer molecular weight on drug release from Polyox tablets.
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 x 10(6)) 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 x 10(6)), 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 x 10(6)), 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 x 10(6)) for drugs for which solubility is below 1%. PEO tablets (MW = 2.0 x 10(6)) 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 x 10(6)) using a drug which has a solubility of less than 0.1%.
Kim
C J
CJ
School of Pharmacy, Temple University, Philadelphia, Pennsylvania 19140, USA.
D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005079:Excipients; D008970:Molecular Weight; D011092:Polyethylene Glycols; D020156:Salicylic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics; D012995:Solubility; D000077589:Sulfathiazole; D013432:Sulfathiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D013607:Tablets; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics; D014867:Water / Q000737:chemistry
D005079:Excipients; D013432:Sulfathiazoles; D013607:Tablets; D014867:Water; D004008:Diclofenac; D011092:Polyethylene Glycols; D013806:Theophylline; D020156:Salicylic Acid; D000077589:Sulfathiazole