Enabling Personalized Dose Formulation by Evaporative Crystallization Process.

PURPOSE: Evaluating a solution-based drug impregnation strategy for individualized dose formulation of warfarin sodium isopropanol (WS-IPA), a drug with a narrow therapeutic index, using microcrystalline cellulose (MCC) placebo tablets as porous carrier.

METHODS

Two formulation strategies were investigated: Add dissolved WS-IPA dropwise to a tablet, followed by solvent evaporation (M1) and dropwise addition coupled with antisolvent crystallization (M2). The tablets were characterized using powder X-ray diffraction and Raman spectroscopy for solid-form assessment. Scanning electron microscopy with energy-dispersive spectroscopy was used to visualize drug distribution and morphology. Principal component analysis was applied for Raman spectra to identify spectral differences and developed partial least squares (PLS) regression to determine WS-IPA content.

RESULTS

M1 resulted in amorphous WS-IPA under the conditions studied. In contrast, the antisolvent crystallization strategy (M2) promoted the formation of crystalline WS-IPA within the MCC tablets. The M2 tablets met USP dissolution requirements similar to commercial tablets (Coumadin®). External Raman PLS model validation demonstrated the potential for non-destructive WS-IPA content estimation across individualized doses, with a Root Mean Square Error of Prediction of 0.35 mg.

CONCLUSION

M2 with Raman-based process analytical technology enabled crystallization control and non-destructive tablet analysis for the flexible production of individualized solid dosage forms of WS-IPA.