Formulation by Design Approach for Fizzy Granules Using Statistical Optimization Methodologies

Abstract

Context: Patient compliance is a major problem in the administration of medicines to pediatric patients mainly
due to bitter taste or fear of medication. Therefore, novel formulation development based on current industrial
practices is need of the hour. Aims: To prepare fizzy granules of amoxicillin trihydrate using formulation by
design (FbD) concept to increase the patient compliance in pediatrics. Settings and Design: Critical process
parameters were selected using Plackett–Burman design while their concentrations were optimized by application
of response surface methodology using 20 confirmatory runs, which indicated very high degree of prognostic
ability of statistical optimization. Low and high levels of each factor represented maximal and minimal settings of
wide operational ranges. Materials and Methods: Formulations were prepared by non-aqueous wet granulation
method. Statistical Analysis Used: Statistical methodologies were used to screen significant variables and
responses, which affect the quality of fizzy formulation. Sodium bicarbonate, polyvinyl pyrrolidone, and lactose
were selected as critical excipients, based on t-coefficient values as obtained through Plackett–Burman design.
Then, 33 central composite design was employed to systematically optimize these variables and desired quality
attributes, particle size (PS), and fizzy time. Contour plots were drawn, and optimum concentrations of selected
excipients were determined using point optimization feature. Results: Developed polynomial mathematical
models were found suitable to define effervescence time and PS of the optimized formulation with 98.46% and
91.24% validity. Conclusion: FbD concept was successfully applied for the development of fizzy granules as per
current quality practices prevailing in pharmaceutical industries.