Abstract

ISOSORBIDE DINITRATE: PHARMACOLOGY, DRUG DELIVERY, QUALITY EVALUATION, CLINICAL APPLICATIONS, AND EMERGING ADVANCES

Satti Naga Santhosh Reddy*, Jagathi Shyam Venkata Nadh, Chakka Sri Satya Ratna Navya Lakshmi, Tanapathi Sai Sri Mounika, Nuthulapati Bunny, Satti Varshitha

ABSTRACT

In the present study we attempted to understand the pharmacology and quality aspects involved in the formulation of the isosorbide dinitrate (ISDN). Cardiovascular disorders account for nearly one-third of global deaths, with ischemic heart disease being the most prevalent form. Isosorbide dinitrate (ISDN), an organic nitrate prodrug, remains a cornerstone therapy for angina pectoris, coronary heart disease, and adjunctive heart failure management. Mechanistically, ISDN is metabolized by aldehyde dehydrogenase-2 to release nitric oxide, which activates soluble guanylyl cyclase, elevating cGMP and triggering protein kinase G-mediated vasodilation through calcium efflux and myosin light chain kinase inhibition. This dual arterial and venous relaxation reduces cardiac preload and afterload, relieving anginal symptoms. Pharmacokinetically, ISDN shows variable oral bioavailability (10–90%) due to extensive hepatic first-pass metabolism, ashort plasma half-life of about one hour, and renal elimination. ISDN is developed for a variety of delivery systems, including parenteral infusions for acute critical care, transdermal patches for continuous systemic delivery, sustained-release oral systems for prophylaxis, and sublingual/buccal wafers and films for quick emergency relief. Formulation stability and consistency are guaranteed by strict quality control, which includes pre-compression flow testing, FTIR/DSC characterization, dissolution and diffusion tests, and HPLC/UPLC-based assay techniques. ISDN has been shown to be effective in treating acute coronary syndrome, stable angina, and heart failure with reduced ejection fraction when used in conjunction with hydralazine. Black patient populations have benefited most from this treatment. Nitrate-free dosing intervals are necessary since nitrate tolerance is still the main clinical constraint. Future tailored and optimized ISDN treatments are being shaped by recent developments in sustained-release, transdermal, and nanoparticle-based formulations as well as AI-assisted formulation design and enhanced analytical detection of breakdown products.

Keywords: Isosorbide dinitrate, angina pectoris, nitric oxide, vasodilation, cardiovascular therapy, drug delivery, quality control, dissolution, tablet evaluation.