Information from the abstract
Background: Isosorbide dinitrate (ISDN) and hydralazine hydrochloride (HDZ) are dual cardiovascular drugs used to treat heart failure. However, the drugs have limitations such as short plasma half-life, low bioavailability, and potential for tolerance of the nitrate component. To address the need for prolonged drug release, a floating dual-compartment drug delivery system was developed to provide controlled drug release under simulated gastric dissolution conditions. Objectives: This study aimed to develop floating dual-compartment devices (FDCDs) to contain ISDN and HDZ gel and modify drug release under simulated gastric conditions. Methods: The FDCD was designed in a cylindrical shape consisting of an air chamber on the upper part for floating ability, and two compartments for loaded drug gel and controlling the drug release rate. Fused deposition modeling (FDM) was selected to fabricate FDCDs using polylactic acid (PLA) filament. The ISDN formulation varied the ratio of polyvinylpyrrolidone (PVP) to achieve drug release for 12 h. The HDZ formulation was optimized by varying the ratio of PVP and hydroxypropyl methylcellulose (HPMC) to extend drug release at 24 h. Results: The shape dimension and weight variation in the FDCDs showed low standard deviation (SD). FDCDs exhibited immediate floating, resisted overturning, and demonstrated in vitro floating ability for more than 24 h. The formulation ISDN3 at a PVP: drug: water ratio of 5:2:3 exhibited complete release at 12 h, while the formulation of HDZ1 at an HPMC: PVP: drug: water ratio of 0.3:2.5:2:5.2 showed complete release within 24 h. The ISDN3- and HDZ1-loaded FDCDs demonstrated prolonged release behavior, with ISDN and HDZ release profiles showing the best fit to the zero-order and Higuchi models, respectively, based primarily on the coefficient of determination (R2), while root mean square error (RMSE) was used as a complementary measure of fitting error. Conclusions: These findings suggest that the developed dual-drug-loaded FDCD has potential as a dual-drug oral delivery platform for simultaneous delivery of ISDN and HDZ with prolonged drug release characteristics and further development of oral combination drug delivery systems.
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Related topics: Advanced Drug Delivery Systems · Additive Manufacturing and 3D Printing Technologies · Inhalation and Respiratory Drug Delivery
Thai researcher and institutional participation
Dareena Jaiseri · Supusson Pengnam · Praneet Opanasopit · Phuvamin Suriyaamporn · Chaiyakarn Pornpitchanarong · Theerasak Rojanarata · Boonnada Pamornpathomkul · Prasopchai Patrojanasophon · Teeratas Kansom · Thapakorn Charoenying · Silpakorn University
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