Formulation and Evaluation of Ranolazine Extended-Release Matrix Tablets Employing Eudragit® L100-55

Abstract

Background: Ranolazine is an anti-anginal agent widely used for the management of chronic stable angina. However, its relatively short biological half-life and high solubility in acidic gastric conditions result in rapid drug release, frequent dosing requirements, and fluctuations in plasma drug concentrations. The present study aimed to develop and evaluate an extended-release matrix tablet of Ranolazine using a pH-dependent polymer system to achieve controlled drug release over 24 hours.

Methods: Extended-release matrix tablets containing 500 mg of Ranolazine were formulated by wet granulation using Eudragit L100-55 as a pH-dependent release-retarding polymer, Hydroxypropyl Methylcellulose (HPMC 5 cps) as a pH-independent binder, and sodium hydroxide as a neutralizing agent. The prepared formulations were evaluated for pre-compression and post-compression parameters, including flow properties, hardness, friability, weight variation, drug content, and in vitro dissolution characteristics. Drug–excipient compatibility was assessed using Fourier Transform Infrared Spectroscopy (FTIR). Dissolution profiles were analyzed using various kinetic models, and the optimized formulation was compared with a marketed extended-release product (Ranozex®) using similarity (f₂) and difference (f₁) factors. Accelerated stability studies were performed according to ICH guidelines.

Results: FTIR studies confirmed the absence of significant drug–excipient interactions, indicating compatibility between Ranolazine and the selected excipients. All formulations exhibited acceptable pharmaceutical characteristics and complied with pharmacopoeial specifications. Among the developed formulations, the optimized batch demonstrated sustained drug release extending up to 24 hours with 97.72% cumulative drug release. Drug-release kinetics were best described by the Higuchi model, indicating diffusion-controlled release behavior. The Korsmeyer–Peppas release exponent (n = 0.776–0.950) suggested a non-Fickian anomalous transport mechanism involving both diffusion and polymer relaxation. The optimized formulation exhibited dissolution profile similarity with the marketed product, showing an f₂ value of 85.95 and an f₁ value of 2.29. Stability studies revealed no significant changes in physical appearance, drug content, or dissolution characteristics after storage under accelerated conditions.

Conclusion: The study successfully developed a stable and effective extended-release matrix tablet of Ranolazine employing Eudragit L100-55 and HPMC 5 cps. The optimized formulation provided controlled drug release over 24 hours, exhibited diffusion-controlled release kinetics, and demonstrated dissolution equivalence to the marketed product. These findings support the potential application of the developed formulation as a once-daily oral extended-release dosage form for improved management of chronic stable angina.