TY - JOUR

T1 - Physical stability and enthalpy relaxation of drug-hydroxypropyl methylcellulose phthalate solvent change co-precipitates

AU - Sertsou, Gabriel

AU - Butler, James

AU - Hempenstall, John

AU - Rades, Thomas

PY - 2003/1/1

Y1 - 2003/1/1

N2 - The poorly water-soluble drug GWX was co-precipitated with hydroxypropyl methylcellulose phthalate (HPMCP) using a solvent change method. The two-co-precipitate formulations made, with drug-HPMCP ratios of 2:8 and 5:5, were analysed using modulated temperature differential scanning calorimetry. They were found to consist of completely amorphous solid solution and a mixture of amorphous solid solution, crystalline drug and amorphous drug, respectively. Stability with respect to crystallization of the two co-precipitates and pure amorphous drug made by quench cooling was compared by storing preparations at 25°C and 40°C, under vacuum over P2O5, and at 75% relative humidity (r.h.). Humidity (75% r.h. compared with dry) had a larger influence on crystallization of the amorphous drug than temperature (25°C compared with 40°C). The solid solution phase in co-precipitates had a relatively higher stability than amorphous drug alone, with respect to crystallization, in presence of the plasticizer water, and crystalline drug. These findings were partly explained by evidence of decreased molecular mobility in the amorphous solid solution with respect to amorphous drug alone, using enthalpy relaxation measurements. An an ageing temperature of 65°C, the calculated half-life for enthalpy relaxation of the 2:8 drug-HPMCP ratio co-precipitate was about 6 orders of magnitude greater than that of amorphous drug alone, indicating a large difference in relative molecular mobility.

AB - The poorly water-soluble drug GWX was co-precipitated with hydroxypropyl methylcellulose phthalate (HPMCP) using a solvent change method. The two-co-precipitate formulations made, with drug-HPMCP ratios of 2:8 and 5:5, were analysed using modulated temperature differential scanning calorimetry. They were found to consist of completely amorphous solid solution and a mixture of amorphous solid solution, crystalline drug and amorphous drug, respectively. Stability with respect to crystallization of the two co-precipitates and pure amorphous drug made by quench cooling was compared by storing preparations at 25°C and 40°C, under vacuum over P2O5, and at 75% relative humidity (r.h.). Humidity (75% r.h. compared with dry) had a larger influence on crystallization of the amorphous drug than temperature (25°C compared with 40°C). The solid solution phase in co-precipitates had a relatively higher stability than amorphous drug alone, with respect to crystallization, in presence of the plasticizer water, and crystalline drug. These findings were partly explained by evidence of decreased molecular mobility in the amorphous solid solution with respect to amorphous drug alone, using enthalpy relaxation measurements. An an ageing temperature of 65°C, the calculated half-life for enthalpy relaxation of the 2:8 drug-HPMCP ratio co-precipitate was about 6 orders of magnitude greater than that of amorphous drug alone, indicating a large difference in relative molecular mobility.

UR - http://www.scopus.com/inward/record.url?scp=0346033432&partnerID=8YFLogxK

U2 - 10.1111/j.2042-7158.2003.tb02431.x

DO - 10.1111/j.2042-7158.2003.tb02431.x

M3 - Journal article

C2 - 12625865

AN - SCOPUS:0346033432

VL - 55

SP - 35

EP - 41

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 1

ER -