Development of the new solid dosage form of cholecalciferol by the QBD approach

In this study, it is aimed to develop a solid dosage form that has increased stability by the encapsulation method of the micro-level dissolved cholecalciferol within an oily phase. In this regards, Cholecalciferol 100.000 IU concentrate dry powder formed an intermediate product and Cholecalciferol 2000 IU Tablet finished product formulation and manufacturing process development studies were carried out with the "Quality by Design (QbD)" approach. Quality and design (QbD) is a systematic scientific approach to controlling and understanding formulation and process variables in product design and development. Critical Quality Attributes (CQAs), formulation variables that affect critical quality attributes and Critical Process Parameters (CPPs) were analyzed based on Failure Mode and Effects Analysis (FMEA) risk assessment method. In the pre-formulation and formulation studies, the production process method was selected and some independent formulation and process variables were determined by "one factor at a time" experiments. After the initial risk assessments, in the laboratory-scale formulation studies, the factors that affecting the critical quality characteristics at a high rate were idendified for the subsequent optimization studies. The spraying of colecalciferol-containing microemulsion on the carrier excipients and drying process were selected for optimization study which will be performed by using Minitab program. The product temperature in the spraying process, drying process time and inlet air absolute humidity parameters were determined as a factor and a working design was created by using Minitab> DOE> Screening module. 13 scale-up batches in the study design were produced and the results of the analysis were entered as a data set in the Minitab program. The statistical analysis of the data sets revealed the relationship between the factors and the critical quality characteristics and the effect power of the each factor. The effects of product temperature in the spraying process and drying process time on the CQA responses that are BHT assay, Cholecalciferol assay and Cholecalciferol dissolution were statistical significant since their p values were less than 0.05. Minitab programının istatistiksel olarak anlamlı model aracılığı ve çeşitli görsel grafikleri ile bu faktörlerin güven aralıkları, kurutma prosesi süresi için 90-140 dakika, spreyleme sırasında ürün sıcaklığı için 27-33℃ olarak belirlenmiştir. After the pre-formulation, formulation, scale-up and determination of safe ranges of the most critical factors with the Minitab 18 program, a control strategy was developed with the findings of all these systematic studies. Finally, the developed formulation and production process was confirmed by the production and control of the 3 replicated pilot scale series based on the control strategy in the process validation study.