I am actually working on pharmaceutical formulations with thermoplastic polymers such as "copovidone or Kollidon VA64 and active ingredients like "Paracetamol". When i was running DSC with pure polymers, i used to do heat-cool-heat cycle (25-250 at 10°C/ min) in order to obtain the glass transition temperature (103 °C). Now, I am producing extrudates of KVA64 with Paracetamol and I am trying to determine solid state change of the Paracetamol (which is crystalline and have melting peak at 170°C) and check if I obtained a solid amorphous dispersion. However, by applying the heat-cool-heat cycle method to the physical mixture or the extrudates, i only fitnd in the 2nd heat a glass transition temperature without the melting peak characteristic of the Paracetamol even though on XRD there a some cristalline peaks. I think during the 1st heating, I amorphized the Paracetamol within the copovidone and the 2nd heating displays the thermal profile of this in-situ solid amorphous dispersion and not my original product. Could you suggest me some solutions to this issue? Thanks in advance
Yes, many organic substances do not crystallize from melt during cooling. But what is the problem? If you want to determine the physical state of paracetamol in the mixture, then you certainly should evaluate it from the FIRST heating run which corresponds to "as received" material.
The second heating run allows you to determine the Tg of KVA64, it has nothing to do with the properties of paracetamol.
During the 1st heating, the melting peak of the paracetamol is not evident because it interferes with some thermal events of the polymer. I want to have the glass transition temperature of KVA64 and the melting peak of paracetamol both displayed on the curve wich is the real solid state of my compound.
Can I remove thermal history of the polymer whithout going to higher temperatures (which avoids melting of paracetamol) or by just applying an isotherm at 100°C?
Can you attach a DSC record? It is unclear to me what thermal events can interfere with paracetamol melting. Perhaps some small "relaxation" effects of the polymer above the Tg?
Maybe first heating to ca. 110°C would be sufficient to get rid of relaxation artifacts without paracetamol melting.
I would expect nice sharp melting endotherm for crystalline paracetamol. Amorphous paracetamol can be pretty invisibile in DSC (Tg's are sometimes really hard to determine).
Have you compared the DSC thermograms of different Drug-Polymer ratios? Why your'e fixed to achieve a sharp peak (endotherm) which is unlikely if a part of drug got converted to amorphous form due to polymer interaction. In a pure drug thermogram, degradation follows a sharp melting point peak whereas in a drug-polymer mixture the intermolecular forces within drug changes and a shift in Tg and Melting point is expected. The only solution is compare the DSC DSC thermograms of different Drug-Polymer ratios.
Tibor Dubaj I attached the DSC record , from the 1st heating it appears that relaxation of KVA64 occurs at the melting region of paracetamol so I dont know if heating until 110°C will be enough.
Packiaraj Jeyachandran Manohari The problem is that the physical mixture and the extrudate (with the same ratio) show same DSC pattern (same Tg).
Thanks in advance
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