Nghiên cứu bào chế và đánh giá hệ vi tự nhũ (SMEDDS) chứa olmesartan medoxomil

Olmesartan medoxomil (OLM) is a critical angiotensin II receptor blocker used for chronic hypertension, yet its therapeutic efficacy is often compromised by low water solubility and poor oral bioavailability. This inherent characteristic limits its dissolution and absorption, directly impacting clinical outcomes. Developing innovative drug delivery systems is thus paramount to overcome these pharmacokinetic challenges. This study addresses this pressing need by focusing on the development and comprehensive evaluation of a self-microemulsifying drug delivery system (SMEDDS) designed to significantly enhance OLM's solubility and improve its in vitro absorption profile.

Researchers and practitioners in pharmaceutical formulation, drug delivery, pharmacokinetics, and pharmacology, particularly those interested in enhancing the solubility and bioavailability of poorly water-soluble drugs.

The persistent challenge of Olmesartan medoxomil (OLM)'s poor water solubility and low oral bioavailability necessitated the exploration of advanced formulation strategies. This research focused on developing and evaluating a self-microemulsifying drug delivery system (SMEDDS) to overcome these limitations. The methodology involved a systematic approach, starting with extensive screening of various oils, surfactants, and co-surfactants based on their solubility and emulsification capabilities. Subsequently, pseudo-ternary phase diagrams were constructed to identify optimal component ratios for stable microemulsions. The study then proceeded to load OLM into promising SMEDDS formulations (1-3% w/w) and rigorously characterize them. Key characterization parameters included particle size, polydispersity index (PDI), zeta potential, thermodynamic stability, and X-ray diffraction (XRD) analysis to confirm OLM's physical state within the system. Crucially, the in vitro drug release was assessed in a gastrointestinal simulation system (GISS).
Results revealed that the optimized A5/B1 SMEDDS formulation, composed of Capryol 90, Croduret 40, and Transcutol HP, successfully loaded 2% w/w OLM. This system demonstrated rapid self-emulsification, forming nano-sized particles (14-17 nm) with a low PDI (<0.1) and stable zeta potential (~10 mV), indicative of a highly uniform and stable dispersion. The formulation exhibited excellent thermodynamic stability, and XRD analysis confirmed the dissolution of OLM within the SMEDDS, eliminating recrystallization. Furthermore, the A5/B1 SMEDDS showed remarkable in vitro release, with 80% of OLM released within 10 minutes and 100% within 50 minutes in GISS, significantly outperforming the raw drug and a reference product. This comprehensive development and evaluation of a robust SMEDDS for Olmesartan medoxomil provides a strong foundation for optimizing its oral delivery, potentially leading to enhanced therapeutic outcomes for patients with hypertension by improving drug absorption and bioavailability. The insights gained from the ternary phase diagram construction and detailed characterization lay the groundwork for future clinical translation and refinement of this novel formulation.