TY - JOUR
T1 - Interlaboratory validation of small-scale solubility and dissolution measurements of poorly water-soluble drugs
AU - Andersson, Sara B. E.
AU - Alvebratt, Caroline
AU - Bevernage, Jan
AU - Bonneau, Damien
AU - Mathews, Claudia da Costa
AU - Dattani, Rikesh
AU - Edueng, Khadijah
AU - He, Yan
AU - Holm, René
AU - Madsen, Cecilie Maria
AU - Müller, Thomas
AU - Muenster, Uwe
AU - Müllertz, Anette
AU - Ojala, Krista
AU - Rades, Thomas
AU - Sieger, Peter
AU - Bergström, Christel A. S.
N1 - Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - The purpose of this study was to investigate the interlaboratory variability in determination of apparent solubility (Sapp) and intrinsic dissolution rate (IDR) using a miniaturized dissolution instrument. Three poorly water-soluble compounds were selected as reference compounds and measured at multiple laboratories using the same experimental protocol. Dissolution was studied in fasted-state simulated intestinal fluid and phosphate buffer (pH 6.5). An additional 6 compounds were used for the development of an IDR measurement guide, which was then validated with 5 compounds. The results clearly showed a need for a standardized protocol including both the experimental assay and the data analysis. Standardization at both these levels decreased the interlaboratory variability. The results also illustrated the difficulties in performing disc IDR on poorly water-soluble drugs because the concentrations reached are typically below the limit of detection. The following guidelines were established: for compounds with Sapp >1 mg/mL, the disc method is recommended. For compounds with Sapp <100 μg/mL, IDR is recommended to be performed using powder dissolution. Compounds in the interval 100 μg/mL to 1 mg/mL can be analyzed with either of these methods.
AB - The purpose of this study was to investigate the interlaboratory variability in determination of apparent solubility (Sapp) and intrinsic dissolution rate (IDR) using a miniaturized dissolution instrument. Three poorly water-soluble compounds were selected as reference compounds and measured at multiple laboratories using the same experimental protocol. Dissolution was studied in fasted-state simulated intestinal fluid and phosphate buffer (pH 6.5). An additional 6 compounds were used for the development of an IDR measurement guide, which was then validated with 5 compounds. The results clearly showed a need for a standardized protocol including both the experimental assay and the data analysis. Standardization at both these levels decreased the interlaboratory variability. The results also illustrated the difficulties in performing disc IDR on poorly water-soluble drugs because the concentrations reached are typically below the limit of detection. The following guidelines were established: for compounds with Sapp >1 mg/mL, the disc method is recommended. For compounds with Sapp <100 μg/mL, IDR is recommended to be performed using powder dissolution. Compounds in the interval 100 μg/mL to 1 mg/mL can be analyzed with either of these methods.
KW - Journal Article
U2 - 10.1016/j.xphs.2016.03.010
DO - 10.1016/j.xphs.2016.03.010
M3 - Journal article
C2 - 27112289
SN - 0022-3549
VL - 105
SP - 2864
EP - 2872
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 9
ER -