Solubility of sparingly-soluble ionizable drugs

被引:233
作者
Avdeef, Alex [1 ]
机构
[1] PION INC, Woburn, MA 01801 USA
关键词
sparingly-soluble ionizable compounds; pH-dependent solubility; solubility equations; aggregation; complexation; shake-flask method; miniaturized shake-flask method; dissolution template titration method; micro dissolution method; PH-METRIC SOLUBILITY; BILE-SALTS; PARTITION-COEFFICIENTS; HYDROCHLORIDE SALTS; BETA-CD; DISSOLUTION; BEHAVIOR; COMPLEXATION; IONIZATION; PROFILES;
D O I
10.1016/j.addr.2007.05.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The experimental and computational basis of the pH-dependent measurement of solubility of sparingly-soluble ionizable drugs is reviewed. Recently described compound-sparing (but still accurate) approaches, suitable for application in preclinical development, and appropriate for the analysis of solubility of "problematic" molecules, are critically examined. A number of useful experimental methods are reviewed, including the miniaturized shake-flask microtitre plate, the micro solubility self-calibrating direct UV, potentiometric, and the micro dissolution methods. Several molecules were selected as case studies to illustrate important concepts, with re-analysis of literature data using recently established computational tools. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:568 / 590
页数:23
相关论文
共 90 条
[71]  
Serajuddin ATM., 2002, HDB PHARM SALTS PROP, P135
[72]   Solubilization and dissolution of insoluble weak acid, ketoprofen: Effects of pH combined with surfactant [J].
Sheng, Jennifer J. ;
Kasim, Nehal A. ;
Chandrasekharan, Ramachandran ;
Amidon, Gordon L. .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2006, 29 (3-4) :306-314
[73]   SALT AND MESOPHASE FORMATION IN AQUEOUS SUSPENSIONS OF LAURIC ACID [J].
SMITH, SW ;
ANDERSON, BD .
PHARMACEUTICAL RESEARCH, 1993, 10 (10) :1533-1543
[74]  
Stahl PH, 2006, Polymorphism: in the pharmaceutical industry, P309
[75]  
Streng W.H., 2001, Characterization of Compounds in Solution, Vfirst
[76]   GENERAL TREATMENT OF PH-SOLUBILITY PROFILES OF WEAK ACIDS AND BASES AND THE EFFECTS OF DIFFERENT ACIDS ON THE SOLUBILITY OF A WEAK BASE [J].
STRENG, WH ;
HSI, SK ;
HELMS, PE ;
TAN, HGH .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1984, 73 (12) :1679-1684
[77]   Determination of solution aggregation using solubility, conductivity, calorimetry, and pH measurements [J].
Streng, WH ;
Yu, DHS ;
Zhu, CY .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1996, 135 (1-2) :43-52
[78]   Solubilizing excipients in oral and injectable formulations [J].
Strickley, RG .
PHARMACEUTICAL RESEARCH, 2004, 21 (02) :201-230
[79]   High throughput solubility measurement with automated polarized light microscopy analysis [J].
Sugano, Kiyohiko ;
Kato, Teruhisa ;
Suzuki, Kentaro ;
Keiko, Kako ;
Sujaku, Tetsujo ;
Mano, Takashi .
JOURNAL OF PHARMACEUTICAL SCIENCES, 2006, 95 (10) :2115-2122
[80]   SOLUBILIZATION OF THIAZOLOBENZIMIDAZOLE USING A COMBINATION OF PH ADJUSTMENT AND COMPLEXATION WITH 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN [J].
TINWALLA, AY ;
HOESTEREY, BL ;
XIANG, TX ;
LIM, K ;
ANDERSON, BD .
PHARMACEUTICAL RESEARCH, 1993, 10 (08) :1136-1143