Study of Critical Formulation and Process Parameters Influencencing Mini-Tablet Preparation Using Concept of QbD

Abstract

Mini-tablets can be defined as tablets with a diameter less than 4mm. Mini-tablets affords us various benefits such as easy to swallow, easy to manufacture and are observed to have high stability when compared to pellets. This project is based on identification of critical process and formulation parameter which may influence the mini-tablet formulation by applying concept of QbD. Initially patent review was done in which we observed that all the patents related to the model drug are available as single unit dosage form, therefore to bypass the patents we have formulated multiple unit tablets. After the selection of dosage form, we have identified CQAs of material and process by execution the risk assessment. 3 manufacturing methods were evaluated and based on the data obtained wet granulation method was selected. Compression of mini-tablets were executed with the assistance of 3mm multiple tip tooling having 10 tips. From the trial we observed that the 20 mini-tablets are required to deliver 100mg of drug, hence capsule was selected since offers good stability due to its shell, accuracy of dosing and also eases of administering. Risk factors were evaluated and updated CQAs was obtained. Based on the updated CQAs factors imparting high risk were selected for DoE trials. Pharmatose 200M: Avicel PH101, Amount of water (%w/w), Kneading time (sec) were selected for DoE trials as factors and BD, CI, PSD (% Retained on 60#), Weight variation (%RSD), DT, Dissolution (at 30 min) were considered as responses. From the DoE trial data we observed that the selected factor have a huge impact on DT and dissolution. An optimized batch was selected based on the data obtained after the DoE trials. After the preparation of optimized batch, dissolution of optimized batch and RLD product was conducted, in which we observed that the product is similar. Futures on pellets were prepared with the same optimized formula and data obtained are compared with optimized mini-tablets. Survey was also conducted to acquire the acceptance of mini-tablets by various age groups.