USE OF SUBAMBIENT DIFFERENTIAL SCANNING CALORIMETRY TO MONITOR THE FROZEN STATE BEHAVIOR OF AMINO-ACIDS IN SIMULATED FREEZE-DRYING CONDITIONS

The purpose of this study was to evaluate the frozen behaviour of amin o acids and their blends with other excipients commonly? used as freez e-drying cryoprotectants or bulking agents in simulated lyophilization conditions. Subambient differential scanning calorimetry was utilized as an analytical tool to evaluate the phenomena from a qualitative po int of view. The differential scanning calorimetry scans were performe d at rates comparable to those generally practicable in industrial lyo philization plants. Different crystallization behaviours were observed in amino acid solutions : during the freezing ramp (e.g. L-glycine, L -alanine, L-serine), during the heating ramp (e.g. L-glutamic acid), o r-during both (e.g. L-histidine). The phenomena can be influenced by p H changes as well as bq, the addition of other excipients : crystalliz ation events could be specified or fully inhibited. This means that th e final physical state of the freeze-dried product (amorphous, crystal line or partly amorphous/partly crystalline) can be tailor ecl by accu rately choosing not only the freeze-drying parameter:er conditions, br it also the composition of the solution to be I?lyophilized. The resul ts point out that it is possible to reduce the number of ?preformulati on activities required to design the most appropriate formulation? for each new drug candidate.