Abstract/Summary

The current work presents the formulation development methodology for Orally Disintegrating Tablets (ODTs) using Design of Experiment (DoE). The statistical software JMP was used to design the experiments and analyse the data for producing sodium Ibuprofen freeze-dried ODTs. In the first stage, several pure excipients (polymers, amino acids, and polyols) were freeze-dried and the quality attributes of the cakes were evaluated. Four critical quality attributes (CQAs) were determined based on the target profile: disintegration time, mechanical strength, moisture uptake, appearance. In the second stage, the placebo tablets comprising sodium alginate, alanine, and mannitol (working as a matrix shape-former and lyo-/cryo-protectors), were designed using Mixture DoE, freeze-dried and characterized to identify the optimal combination of the excipients. In the third stage, the ODTs containing sodium Ibuprofen were designed within a reduced design space to optimize the formulation. The wettability and dissolution of the ODTs were studied. The proposed methodology enabled the estimation of working design space and facilitated the production of freeze-dried ODTs with the required quality attributes. Sodium alginate was identified as the key excipient in the formulation, affecting all CQAs. The optimal combination of sodium alginate, alanine and mannitol corresponding to the desirable target profile was found (30%:40%:30%).