Effect of Formulation Variables on Dissolution of Water-Soluble Drug from Polyelectrolyte Complex Beads

This study was planned to develop chitosan-based polyelectrolyte complex (PEC) beads for the prolonged release of the water-soluble drug, verapamil HCl (VPL).The PEC beads were prepared by an ionic gelation method using positively charged chitosan (CH) and negatively charged sodium alginate (ALG), carboxymethylcellulose sodium (CMC), and k-carrageenan (CAR).The surface morphology was investigated by scanning electron microscopy (SEM), and PEC formation was confirmed by differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy.Gel beads were evaluated for particle size, drug entrapment efficiency, swelling behavior, and in vitro release.The SEM study confirmed that spherical or disc-shaped beads were formed by changing the counterion and pH of the coagulation medium.DSC and FTIR spectroscopy confirmed the PEC formation.The mean particle size was 556-896 µm, and drug entrapment efficiency was more than 80%.The beads showed pH-sensitive swelling with less swelling in hydrochloric acid buffer (pH 1.2) and more swelling in phosphate buffer (pH 7.4).The in vitro release of VPL was very slow in HCl buffer as compared with phosphate buffer.The concentration of chitosan, anionic polymers, and the pH of the coagulation medium significantly affected the size, entrapment efficacy, swelling, and release pattern of PEC beads. MATERIALS AND METHODS MaterialsVerapamil HCl was a kind gift sample from Unicure Pvt. Ltd. (India) and Torrent Pharmaceuticals Ltd. (India).Chitosan (minimum 80% deacetylated) was a gift sample from Mahtani Chitosan Pvt. Ltd. (India).Sodium alginate (ALG) was obtained from Snap Natural and Alginate Pvt. Ltd. (India).-Carrageenan (CAR) was obtained from Sigma-Aldrich (USA).Carboxymethylcellulose sodium (CMC), calcium chloride, aluminum chloride, potassium chloride, and glacial acetic acid were obtained from SD Fine Chem Ltd. (India). Methods Preparation of PEC BeadsThe preparation details of PEC beads are given in Table 1.PEC beads were prepared by an ionic gelation method using varied concentrations (0.5%, 1%, and 1.5% w/w) of CH along with fixed concentrations of ALG, CMC, and CAR in the presence of calcium, aluminum, and potassium as counter ions.The amount of VPL was kept constant (1% w/v).Homogeneous aqueous solutions of CH and calcium chloride/aluminum chloride/potassium chloride were