The purpose of this research was to prepare Urapidil loaded Chitosan Nanoparticles for controlled release of drug, to improve the solubility, reduce the dosing frequency, thereby increasing patient compliance to the therapy.
❖ Urapidil is formulated as Nanoparticles by ionic-gelation method using Chitosan as polymer, Sodium tripolyphosphate as a polyanionic agent (cross linking agent) and the lyophilized nanoparticles filled in hard gelatin capsules.
❖ The preformulation studies like melting point, determination of absorption maximum (268nm) were performed and the results evident that the drug and excipients are stable, safe and effective within the range.
❖ Physical compatibility study showed that the drug and excipients were physically compatible with each other.
❖ The chemical compatibility studies of Urapidil with excipients were physically analyzed by using FTIR Spectrometer. The results of the FTIR study proved that there was no interaction between the drug and polymer.
❖ Standard graph was drawn for Urapidil and it was found that the solutions show linearity (0.9995) and obeyed Beer – Lambert’s law.
❖ Urapidil loaded Chitosan Nanopaticles prepared by ionic-gelation method using Chitosan as a polymer in different concentration (0.1%, 0.15%, 0.2%, 0.25%, 0.3%, 0.4%, and 0.5%). Sodium tripolyphosphate as a polyanionic agent (cross linking agent), Tween 80 as a deaggregating agent.
❖ All seven formulations characterized for percentage yield which found to be within the range of 78.84% to 87.25% and the entrapment efficiency of the formulations was observed between 83.40% to 93.15%. The results showed that the increase in polymer concentration, increase the entrapment efficiency. The entrapment efficiency was found to be higher in F5- 93.15% comparatively with other formulations.
❖ The Solubility analysis of Urapidil was carried out before and after formulation in distilled water and phosphate buffer pH 6.8. The results show that the solubility profile is improved after formulations (from insoluble to slightly soluble) compared with pure drug. Thus the solubility of formulation F5 in distilled water and phosphate buffer pH 6.8 were improved (9.4933 mg/ml and 13.251 mg/ml) respectively.
❖ The in vitro release study was carried out for all seven formulations. The percentage of drug release in formulation F5 was found to be 95.03% at the end of 12h and the release profile was in controlled manner comparatively with other formulations.
❖ Based on the higher entrapment efficiency, drug content and prolonged in vitro drug release F5 was selected as optimized formulation.
❖ The FTIR studies of optimized formulation F5 shows there was no change in the individual peaks of the drug and the excipients. It concludes that there was no chemical interaction between the drug and excipients.
❖ The optimized formulations F5 are characterized for SEM analysis, particle size analysis and zeta potential.
❖ The SEM image showed that nanoparticles were spherical with smooth surface.
❖ The particle size analysis was done by Horriba scientific Nano SZ 100 particle size analyzer showed that mean particle size 188.3 nm and Z- Average 229.0 nm respectively.
❖ The Zeta potential study was done by Horriba scientific Nano SZ 100. The Zeta potential for the optimized formulations F5 was found to be 25.8mV and shows that the formulation is stable.
❖ Flow property measurements (Bulk density, Tapped density, Angle of repose, Carr’s index and Hausner’s ratio) were carried out for Urapidil pure drug and optimized Urapidil loaded Chitosan Nanoparticles. It revealed that the flow property of Chitosan Nanoparticles was good compared with pure drug.
❖ The optimized NPs are filled into “0” size hard gelatin capsules without adding glidant because of its good flow property.
❖ Post formulation parameters (uniformity of weight, disintegration test, drug content, and in vitro drug release) for nano particulate capsules were evaluated. The results were found to be complying with official specifications.
❖ The dissolution data of the optimized formulation was fitted to various kinetic models and the formulation F5 was best fitted to Zero order kinetics. The slope of the Korsmeyer Peppas plot indicating the diffusion was Anomalous diffusion (Non-Fickian diffusion).
❖ The optimized formulation F5 was subjected to accelerated stability study (Refrigeration and Room temperature) No significant change was found in appearance, drug content and entrapment efficiency at the end of 90 days in Refrigerator, Room temperature and at 40ºC±2ºC.
❖ From the overall results, it is clear that the formulations F5 containing 0.3% polymer concentration (Chitosan) is the optimal formulation, as it produces controlled drug release.
FUTURE SCOPE:
1. In-vivo study can be carried out.
2. To study the pharmacokinetic and bio distribution of the drugs.
3. To perform the Bioequivalence study
