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

Abstract

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. INTRODUCTION Polycationic chitosan (CH) is prepared through deacetylation of chitin. Chitosan is an important biopolymer having wide pharmaceutical application (1). Chitosan polyelectrolyte complexes (PEC) are ideal substitutes for covalently cross-linked hydrogels. The formation of a PEC requires only polycationic and polyanionic polymers without catalysts or initiators, and the reaction is generally performed in aqueous solution, which is the main advantage over covalently cross-linked polymeric networks. Therefore PEC offers biocompatibility and avoids the purification step to minimize the toxicity associated with the unreacted covalent cross-linking agents before administration (2–6). The electrostatic attraction between the amino groups of CH and the carboxylic–sulfate groups of anionic polymers is the main interaction leading to the formation of the PEC (7). PECs can be cross-linked by the addition of ions to form ionically cross-linked systems, for instance, calcium ions can be added to alginate (8), and pectin (9) and aluminum ions can be added to carboxymethylcellulose (4). Chitosanbased PECs are well-tolerated systems and can be used in various applications such as drug delivery systems (10). Verapamil hydrochloride (VPL) is a freely water-soluble calcium channel blocker used in the treatment of angina pectoris, hypertension, and supraventricular tachyarrhythmias (11, 12). Upon oral administration, 90% of drug is absorbed from the gastrointestinal tract, but it has low bioavailability of 22% with a biological half-life of 4 ± 1.5 h (13). In the present study, polyelectrolyte complex beads were prepared using CH (cationic polymer) along with three anionic polymers (sodium alginate, carboxymethylcellulose sodium, and k-carrageenan) for prolonged release of the water-soluble drug, VPL. The effect of the concentrations of CH and counter ions and the pH of the coagulation medium on the formation and performance of PEC beads was studied. MATERIALS AND METHODS Materials Verapamil 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 Beads The 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 *Corresponding author. e-mail: rvkulkarni75@yahoo.com ssaleempharm@rediffmail.com dx.doi.org/10.14227/DT190412P21