(M1530-11-71) Development of a Novel Repeat-Action Oral Drug Delivery System for Naproxen and Esomeprazole

Purpose: Repeat-action formulations are intended to release one drug dose initially, followed by a second dose later. This study aimed to develop a repeat-action oral drug delivery system for multiple pulsatile drug releases of naproxen and esomeprazole, which can be used to treat various inflammatory diseases with a decreased risk of gastric ulcers.

Methods: A multi-compartment capsular device that can control the time of drug release was fabricated by a fused deposition modeling 3D printer. Immediate-release tablets of esomeprazole and naproxen, prepared by the conventional wet granulation method, were inserted into the separate compartment of the capsular device. In vitro drug release from the drug delivery system was determined by the paddle method at pH 6.8 (n=6). The in vivo pharmacokinetics were assessed after oral administration of the developed drug delivery systems in Beagle dogs (n=6). The plasma concentrations of esomeprazole and naproxen were simultaneously determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.

Results: The repeat-action drug delivery system consisted of a capsular device combined with conventional IR tablets of esomeprazole and naproxen. The multi-compartment capsular device allowed the immediate release of esomeprazole from one compartment with a large window and the delayed release of naproxen from another compartment enclosed by a polyvinyl alcohol (PVA) layer. The in vitro dissolution test showed the immediate release of esomeprazole, while the release of naproxen was delayed with a lag time (Tlag) of 11.33 ± 1.37 h. The estimated time to release 80% of the drug (T80) was 0.15 ± 0.06 h for esomeprazole and 1.67 ± 0.82 h for naproxen upon drug release. Following oral administration of the repeat-action drug delivery system in Beagle dogs, the immediate absorption of esomeprazole and delayed absorption of naproxen were also observed. The time to maximum plasma concentration (Tmax) of esomeprazole was 0.67 ± 0.67 h, while the Tmax of naproxen was 9.83 ± 2.40 h with a lag time of 4.75 ± 1.17 h.

Conclusion: In summary, a novel repeat-action drug delivery system was developed by combining a 3D-printed capsular device and conventional IR tablets of esomeprazole and naproxen. The immediate release of esomeprazole, followed by a delayed release of naproxen, was demonstrated by in vitro dissolution and in vivo pharmacokinetic studies. This approach holds great promise for developing controlled-release drug delivery systems for various drugs to achieve desired therapeutic efficacy.

Acknowledgements: This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government (MSIT) (No. NRF-2023R1A2C1007013).