Title : Formulation, optimization, and in vitro characterization of chitosan–alginate polyelectrolyte complex microbeads incorporated into a natural hydrophilic matrix for extended oral delivery of an antihypertensive drug
Abstract:
Hypertension is a major chronic cardiovascular disorder requiring prolonged pharmacotherapy and consistent maintenance of therapeutic plasma concentrations to achieve optimal clinical outcomes. Conventional immediate-release antihypertensive formulations often result in fluctuating drug levels, reduced patient compliance, and the necessity for frequent dosing. The present investigation was therefore aimed at developing and evaluating a polymer-engineered multiparticulate extended-release oral delivery system for an antihypertensive drug using chitosan–alginate polyelectrolyte complex (PEC) microbeads embedded within a natural guar gum-based hydrophilic matrix. The formulation strategy was designed to achieve prolonged drug release, improved gastrointestinal residence, and enhanced therapeutic performance for chronic hypertension management.
The antihypertensive-loaded microbeads were prepared by Ca²?-mediated ionotropic gelation of sodium alginate followed by surface complexation with chitosan to produce a diffusion-controlling PEC membrane around the microbeads. The prepared multiparticulate systems were evaluated for particle size distribution, encapsulation efficiency, production yield, micromeritic characteristics, swelling behavior, surface morphology, and in-vitro drug release performance. The optimized formulation demonstrated high encapsulation efficiency (86.5 ± 2.4%), satisfactory production yield, excellent mechanical integrity, and uniform particle size distribution with an average D50 value of approximately 520 µm. Morphological evaluation confirmed the formation of discrete, spherical, and mechanically stable microbeads suitable for oral administration.
In-vitro dissolution studies performed under simulated gastrointestinal conditions revealed minimal drug release in acidic medium (<8% within 2 h), indicating effective protection of the drug under gastric conditions, followed by sustained and controlled release extending up to 24 h with cumulative release approaching 90%. The controlled-release behavior was primarily attributed to the synergistic barrier properties of the chitosan–alginate PEC membrane and the swelling-controlled guar gum hydrophilic matrix. Kinetic modeling of the dissolution data demonstrated that the release profile followed anomalous non-Fickian transport kinetics with Korsmeyer–Peppas release exponent (n = 0.62) and excellent regression coefficient (R² = 0.995), suggesting the involvement of both diffusion and polymer relaxation mechanisms in governing drug release.
Further solid-state characterization studies including FTIR and DSC analysis confirmed molecular dispersion of the drug within the polymeric matrix and revealed the absence of significant drug–excipient incompatibility or chemical interaction. The developed multiparticulate delivery system successfully combined the advantages of polyelectrolyte complexation and natural hydrophilic matrix technology to achieve extended oral delivery of the antihypertensive agent. Overall, the optimized formulation demonstrated promising potential as a long-acting oral therapeutic platform capable of improving patient compliance, minimizing dosing frequency, and maintaining sustained antihypertensive activity for effective chronic hypertension management.
