The use of Thermal Analysis in the Study of Solid Dispersions
- 1 January 1987
- journal article
- research article
- Published by Taylor & Francis in Drug Development and Industrial Pharmacy
- Vol. 13 (9-11) , 1741-1777
- https://doi.org/10.3109/03639048709068690
Abstract
Differential thermal analysis (DTA) has been used to study the properties of seven drug-polyethylene glycol 6000 solid dispersions immediatley after preparation by rapid cooling. PEG 6000 displayed a melting point of 64°C but other, second order transitions occurred at 29 to 40°C and at ∼ -50°C. Melts of chloramphenicol, glutethimide, griseofulvin, indomethacin and paracetamol solidifed to glasses, but phenacetin and phenylbutazone recrystallised. By examining the dispersions at various drug:PEG 6000 ratios, ranges were estimated which corresponded to PEG recrystallisation, PEG fusion, drug recrystallisation and drug fusion. It was predicted that systems which displayed PEG melting endotherms at drug contents of 0 to > 70% drug and drug melting endotherms at contents in excess of 50% drug, made unsuitable solid dispersions because increases in dissolution rate occurred over a limited range of low drug content. Graphs of reciprocal glass transition temperatures (Tg) and dispersion content indicated a transition temperature for PEG 6000 at -71°C. Using this value and the observed Tg values of the drugs, estimates of T- values were compared with observed values throughout the drug:PEG 6000 phase diagrams. Systems where the observed Tg values were higher than calculated Tg values (paracetamol or chloramphenicol) were less prone to age-mediated dissolution changes than those systems where the calculated Tg values exceeded the observed values (glutethimide, griseofulvin or indomethacin).Keywords
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