Chronotherapeutic Design of pH-Sensitive Pulsatile Microparticles for Salbutamol Sulphate in Nocturnal Asthma Management

Abstract

This study investigates the formulation and evaluation of chitosan-based microparticles designed for controlled drug release, utilizing Salbutamol sulphate as a model drug. Core microparticles were synthesized using a water-in-oil (w/o) emulsion method, incorporating various concentrations of chitosan and Span-85, and subjected to different stirring speeds. Coating of the core microparticles was achieved using Eudragit polymers to develop enteric-coated formulations. The particle size and distribution, morphology, drug entrapment efficiency, loading capacity, and percentage yield were systematically analyzed. Scanning Electron Microscopy (SEM) was employed to assess the surface characteristics of the microparticles, while FTIR and DSC studies were conducted to confirm the chemical compatibility and stability of the formulations. Swelling studies revealed significant insights into the water absorption capabilities of the microparticles. Drug release studies were performed under simulated gastrointestinal conditions, with core microparticles demonstrating varied release profiles across different pH levels. The eudragit coated microparticle did not release the drug in acidic pH of stomach, and the Eudragit S100 and R100 coated microparticle showed burst release at pH 7.4 and at pH 5.8 indicating perfect pH sensitive pulsatile drug delivery. The rapid drug release of certain amount of drug in a short period of time after a lag time makes the system ideal for chronotherapeutic drug delivery system. The pharmacokinetic modeling indicated that MSF-4 had the highest zero-order and Higuchi constants, while EMC-3 showed excellent zero-order fit, highlighting its suitability for sustained release. These findings demonstrated the potential of these microparticles for chronotherapeutic drug delivery, providing a versatile platform for targeted and controlled drug administration.