Impact of Ester Promoieties on Transdermal Delivery of Ketorolac

The study synthesized and evaluated different ketorolac ester prodrugs with various promoieties to compare their percutaneous penetration. The prodrugs, including tert-butyl (KT), benzyl (KB), heptyl (KH), and diketorolac heptyl (DKH), were assessed for properties such as melting point, lipophilicity, solubility, enzymatic hydrolysis, skin permeation, and follicle accumulation. KT and KB showed higher skin permeation than ketorolac, with KT achieving 2.5 times and KB 2 times the flux of ketorolac. KH and DKH did not enhance permeation but provided sustained release. KT and KH demonstrated selective follicular absorption, with a threefold increase compared to ketorolac. KB, KH, and DKH slightly increased transepidermal water loss after 7 days, while ketorolac and KT did not affect it. The study concluded that balancing lipophilicity and aqueous solubility is crucial for designing effective prodrugs, alongside ensuring acceptable skin tolerance for safe application.