The use of Thermal Analysis in the Study of Solid Dispersions

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 (T_g) and dispersion content indicated a transition temperature for PEG 6000 at -71°C. Using this value and the observed T_g values of the drugs, estimates of T- values were compared with observed values throughout the drug:PEG 6000 phase diagrams. Systems where the observed T_g values were higher than calculated T_g values (paracetamol or chloramphenicol) were less prone to age-mediated dissolution changes than those systems where the calculated T_g values exceeded the observed values (glutethimide, griseofulvin or indomethacin).