Controlled release of carbamazepine at therapeutically relevant doses using photocrosslinkable polyanhydrides

Epilepsy, one of the most common neurological disorders, is primarily managed with oral antiseizure medications. While effective for many patients, the short half-lives of most anti-epileptic drugs (AEDs) necessitate frequent dosing, leading to poor adherence and compromised seizure control. Controlled-release drug delivery systems offer a promising solution by maintaining consistent drug levels, reducing dosing frequency, and minimizing side effects. Among these systems, photocrosslinkable polyanhydrides are particularly promising due to their unique surface erosion properties across a wide pH range, making them ideal for oral drug delivery applications. These polymers are synthesized from cost-effective starting materials and possess tunable structures. They are also biocompatible, biodegradable, and nontoxic. This study explores the potential of photocrosslinkable polyanhydrides synthesized via thiol-ene 'click' chemistry for the controlled release of carbamazepine. Carbamazepine is an antiepileptic drug with poor water solubility and a narrow therapeutic range. Unlike other controlled-release systems, which faced challenges with high drug loading or compromised polymer integrity, here we demonstrate that photocrosslinkable polyanhydrides can achieve carbamazepine loadings of up to 30 wt% while preserving their surface erosion properties. Cylindrical tablets fabricated from these polymers exhibit tailored release profiles, achieving sustained drug release over 5 to 33 h by adjusting the monomer ratios. Additionally, delayed-release systems are demonstrated, allowing controlled onset times ranging from 2 to 10 h by varying the monomer composition. This approach provides a practical and efficient system for high-dose controlled-release carbamazepine delivery, offering a versatile and effective platform for enhanced epilepsy treatment.