PHARMACOKINETIC EVALUATION OF PH-SENSITIVE P(BA-CO-IA) HYDROGEL MICROSPHERES OF NIFEDIPINE IN RABBITS

Abstract

Background: pH-sensitive hydrogel microspheres have gained increasing attention as advanced drug delivery systems because of their ability to modulate drug release in response to physiological conditions. Nifedipine, a widely prescribed calcium channel blocker for hypertension and angina pectoris, suffers from low oral bioavailability, rapid first-pass metabolism, and short systemic residence time. These limitations often necessitate frequent dosing and contribute to variable therapeutic response, underscoring the need for a sustained-release delivery approach.

Objective: The objective of this study was to develop and evaluate pH-sensitive butyl acrylate-co-itaconic acid (p(BA-co-IA)) hydrogel microspheres for sustained oral delivery of nifedipine and to assess their in vivo pharmacokinetic performance.

Methods: Nifedipine-loaded p(BA-co-IA) hydrogel microspheres were synthesized using a modified suspension polymerization method. In vivo pharmacokinetic evaluation was conducted in healthy male albino rabbits following oral administration of nifedipine standard solution and hydrogel microspheres at a dose of 10 mg/kg. Plasma nifedipine concentrations were quantified using a validated reverse-phase high-performance liquid chromatography method, and pharmacokinetic parameters were calculated using compartmental analysis.

Results: The hydrogel microspheres demonstrated a delayed absorption profile with a higher Tmax (4.98 ± 0.43 h) compared with the standard solution (1.216 ± 0.02 h). Peak plasma concentration was lower for the microspheres (1.43 ± 0.08 µg/mL) than for the standard formulation (2.24 ± 0.01 µg/mL). The elimination half-life was prolonged for the microspheres (4.42 ± 0.96 h versus 2.24 ± 0.5 h), and systemic exposure was markedly enhanced, as reflected by a higher AUC₀–∞ (19.6 ± 0.9 µg·h/mL compared with 10.92 ± 0.16 µg·h/mL). Drug levels remained detectable for up to 24 hours following administration of the sustained-release formulation.

Conclusion: The findings confirmed that pH-sensitive p(BA-co-IA) hydrogel microspheres provided sustained release and improved oral bioavailability of nifedipine, supporting their potential as a promising delivery system for long-term antihypertensive therapy.