In Silico Factorial Screening and Optimization of Chitosan Based Gel for Urapidil Loaded Microparticle using Reduced Factorial Design

Title:In Silico Factorial Screening and Optimization of Chitosan Based Gel for Urapidil Loaded Microparticle using Reduced Factorial Design

Volume: 23 Issue: 10

Author(s): Harekrishna Roy*, Bhabani S. Nayak*Sisir Nandi

Affiliation:

• Institute of Pharmacy and Technology, Salipur, Cuttack 754202, Odisha,India

• Institute of Pharmacy and Technology, Salipur, Cuttack 754202, Odisha,India

Keywords: Sufficient strength of microparticle, in-silico factorial screening, optimization, reduced factorial design, chitosan, pluronic

Abstract:

Objective: Literature study revealed the poor mechanical strength of chitosan-based microparticles. Our research aimed at developing sufficient strength of microparticle with a suitable concentration of chitosan and non-ionic surfactants such as poloxamer-188 (pluronic). It also aimed to develop and study the effect of variables for prepared microparticles utilizing insilico screening methodology, such as reduced factorial design, followed by optimization.

Methods: Preliminary trial batches were prepared with variable concentration of chitosan and poloxamer-188 utilizing cross-linked ion-gelation technique. A 20% w/v sodium citrate solution was used as a cross-linking solution. The resolution-IV of 24-1 reduced factorial design was selected to screen the possible and significant independent variables or factors in the dosage form design. A total number of eight runs were suggested by statistical software and responses were recorded. The responses such as spreadability, pH, viscosity and percentage of drug released at 12 h were considered in the screening study. Based on the result, selected factors were included in the optimization technique, including graphical and numerical methods.

Results: The signified factors based on reduced two-level factorial screening design with randomized subtype, were identified by Half-normal and Pareto chart. Mathematical fitting and analysis were performed by the factorial equation during the optimization process. The validation and fitting of models were suggested and evaluated by p-value, adjusted R2, and predicted R2 values. The significant and non-significant terms were evaluated, followed by finding the optimal concentration and region with yellow color highlighted in an overlay plot. Based on the data obtained by the overlay study, the final formulation batch was prepared and the observed value was found to be pretty much nearer as compared to predicted values. Drug-polymer interaction study included attenuated total reflectance, differential scanning calorimetry, and X-Ray diffraction study.

Conclusion: The principal of the study design was based on finding the prefixed set parameter values utilizing the concept of in-silico screening technique and optimization with a minimal number of trials and study expenses. It concluded that Poloxamer-188 (0.94%), chitosan (2.38%), swelling time (1.81 h), and parts of chitosan (78.51%) in a formulation batch would fulfill the predetermined parameter with specific values.

Cite this article as:

Roy Harekrishna *, Nayak S. Bhabani *, Nandi Sisir , In Silico Factorial Screening and Optimization of Chitosan Based Gel for Urapidil Loaded Microparticle using Reduced Factorial Design, Combinatorial Chemistry & High Throughput Screening 2020; 23 (10) . https://dx.doi.org/10.2174/1386207323666200628110552

DOI https://dx.doi.org/10.2174/1386207323666200628110552	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402