Chitosan based urapidil microparticle development in approach to improve mechanical strength by cold hyperosmotic dextrose solution technique

Abstract

The objective of the study deal with chitosan based microparticle utilizing a novel method mentioned as cold hyperosmotic dextrose solution treatment. The poor mechanical strength of chitosan especially degradation in relation to pH of the medium, poor performance in extended release form as mentioned in literature solved. Microparticles formulated by ion cross-linking technique utilizing chitosan as cationic and small anions such as sodium citrate (SC), sodium sulphate (SS) and sodium tripolyphosphate (STPP) as cross-linkers. Anionic solutions were maintained at 20% w/v along with Dextrose (40% w/v, 15 °C and 2.02 Osmol). The prepared beads were collected on filtration and dried to get microparticles; furthermore subjected for characterization. Those were characterized for surface morphology, entrapment efficiency, and adhesive strength by texture analyzer, in-vitro release study, swelling index, ATR-FTIR, DSC, XRD and in-vivo antihypertensive study by Tail-cuff method. SEM study revealed non symmetrical appearance and porus structure especially in STPP formulation. However, entrapment gradually decreased with increase in chitosan. Whereas, texture analyzer exhibited gradual increase in adhesive strength which indicate obvious improvement in mechanical strength. Similarly, formulations were able prolonged the drug release for sufficient period of time; SC1 exhibited 72.59% at 44 h. From each group the formulation extended rug release for long period subjected to swelling index study; STPP continued to swell as compared to SC and SS. Mean particle size found to be 1.07 μm, 1.35 μm, and 2.17 μm for SC1, SS2 and TP1 microparticles respectively. The selected formulation “SC1” effectively reduced elevated blood pressure as observed in Tail-cuff method.