TY - JOUR
T1 - Evaluation of drug-polymer solubility curves through formal statistical analysis
T2 - comparison of preparation techniques
AU - Knopp, Matthias Manne
AU - Olesen, Niels Erik
AU - Holm, Per
AU - Löbmann, Korbinian
AU - Holm, René
AU - Langguth, Peter
AU - Rades, Thomas
N1 - © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
PY - 2015/1
Y1 - 2015/1
N2 - In this study, the influence of the preparation technique (ball milling, spray drying, and film casting) of a supersaturated amorphous dispersion on the quality of solubility determinations of indomethacin in polyvinylpyrrolidone was investigated by means of statistical analysis. After annealing of the amorphous dispersions above the crystallization temperature for 2 h, the solubility curve was derived from the glass transition temperature of the demixed material using the Gordon-Taylor relationship and fitting with the Flory-Huggins model. The study showed that the predicted solubility from the ball-milled mixtures was not consistent with those from spray drying and film casting, indicating fundamental differences between the preparation techniques. Through formal statistical analysis, the best combination of fit to the Flory-Huggins model and reproducibility of the measurements was analyzed. Ball milling provided the best reproducibility of the three preparation techniques; however, an analysis of residuals revealed a systematic error. In contrast, film casting demonstrated a good fit to the model but poor reproducibility of the measurements. Therefore, this study recommends that techniques such as spray drying or potentially film casting (if experimental reproducibility can be improved) should be used to prepare the amorphous dispersions when performing solubility measurements of this kind.
AB - In this study, the influence of the preparation technique (ball milling, spray drying, and film casting) of a supersaturated amorphous dispersion on the quality of solubility determinations of indomethacin in polyvinylpyrrolidone was investigated by means of statistical analysis. After annealing of the amorphous dispersions above the crystallization temperature for 2 h, the solubility curve was derived from the glass transition temperature of the demixed material using the Gordon-Taylor relationship and fitting with the Flory-Huggins model. The study showed that the predicted solubility from the ball-milled mixtures was not consistent with those from spray drying and film casting, indicating fundamental differences between the preparation techniques. Through formal statistical analysis, the best combination of fit to the Flory-Huggins model and reproducibility of the measurements was analyzed. Ball milling provided the best reproducibility of the three preparation techniques; however, an analysis of residuals revealed a systematic error. In contrast, film casting demonstrated a good fit to the model but poor reproducibility of the measurements. Therefore, this study recommends that techniques such as spray drying or potentially film casting (if experimental reproducibility can be improved) should be used to prepare the amorphous dispersions when performing solubility measurements of this kind.
U2 - 10.1002/jps.24207
DO - 10.1002/jps.24207
M3 - Journal article
C2 - 25363890
SN - 0022-3549
VL - 104
SP - 44
EP - 51
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 1
ER -