Novel polymer series for pharmaceutical applications: alpha-hydroxycarboxylic acid modified polymethacrylates

Enteric-coated dosage forms often suffer from sluggish post-gastric emptying drug release. This work focuses on developing novel enteric polymers as an approach to overcome this problem. The well-known polymer structures of Eudragit® L 100 and L 100-55 were esterified with the α-hydroxycarboxylic acids l-lactic, d,l-lactic and glycolic acid. A resulting partial positive charge arises within the ester linkage, reducing the pK_a value of the polymer. This translates to more facile deprotonation of the carboxylic acid moieties, which enables more rapid polymer dissolution and consequently faster drug release. The dissolution pH threshold was reduced from pH 5.5 for the established Eudragit® L 100-55 to around 5, while the valuable acid-resistant properties of the polymethacrylates were preserved. Capsules filled with paracetamol were coated with the modified polymers as well as with the commercially available materials Eudragit® L 100 and L 100-55. In 0.01 M hydrochloric acid all coated capsules remained intact without any significant drug release. However, in 15 mM phosphate buffer (pH 6.5) the drug release from the formulations based on the novel polymers was significantly enhanced compared to formulations with Eudragit® L 100 and L 100-55. The increased release rate was connected to the faster dissolution of the modified polymers. This novel series of enteric polymers could help to overcome clinical problems associated with the currently used enteric polymers.