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


Harekrishna Roy*, Bhabani Shankar Nayak and Sisir Nandi   Pages 1 - 15 ( 15 )


Objective: Literature study revealed the poor mechanical strength of chitosan-based microparticles. In our research, it aimed and developed 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 in-silico 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 techniques. A 20% w/v sodium citrate solution was used as a cross-linking solution. The resolution-IV of 2 4-1 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 design expert V.11, and responses were recorded. The responses such as spreadability, pH, viscosity, and percentage of drug released at 12 h considered in the screening study. Based on the result, selected factors are 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 halfnormal and Pareto chart. Mathematical fitting and analysis were performed by the factorial equation during the optimization process. The validation and fitting of models suggested by Design expert V.11 and evaluated by p-value, adjusted R2 , and predicted R2 values. The significant and non-significant term was 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 observed value found to be pretty much nearer as compared with predicted values. Drug-polymer interaction study was carried out by Attenuated total reflectance, differential scanning colorimetry, 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 fulfil the predetermined parameter with specific values.


Microparticle, In-Silico Factorial Screening, optimization, chitosan.


Biju Patnaik University of Technology, Rourkela, Odisha-769004, Institute of Pharmacy and Technology, Salipur, Cuttack -754202, Odisha, Department of Pharmaceutical Chemistry, Global Institute of Pharmaceutical Education and Research, Affiliated to Uttarakhand Technical University, Kashipur-244713

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