PURPOSE: To investigate if drug solubility in pharmaceutical excipients used in lipid based formulations (LBFs) can be predicted from physicochemical properties. METHODS: Solubility was measured for 30 structurally diverse drug molecules in soybean oil (SBO, long-chain triglyceride; TGLC), Captex355 (medium-chain triglyceride; TGMC), polysorbate 80 (PS80; surfactant) and PEG400 co-solvent and used as responses during PLS model development. Melting point and calculated molecular descriptors were used as variables and the PLS models were validated with test sets and permutation tests. RESULTS: Solvation capacity of SBO and Captex355 was equal on a mol per mol scale (R (2) = 0.98). A strong correlation was also found between PS80 and PEG400 (R (2) = 0.85), identifying the significant contribution of the ethoxylation for the solvation capacity of PS80. In silico models based on calculated descriptors were successfully developed for drug solubility in SBO (R (2) = 0.81, Q (2) = 0.76) and Captex355 (R (2) = 0.84, Q (2) = 0.80). However, solubility in PS80 and PEG400 were not possible to quantitatively predict from molecular structure. CONCLUSION: Solubility measured in one excipient can be used to predict solubility in another, herein exemplified with TGMC versus TGLC, and PS80 versus PEG400. We also show, for the first time, that solubility in TGMC and TGLC can be predicted from rapidly calculated molecular descriptors.
PURPOSE: To investigate if drug solubility in pharmaceutical excipients used in lipid based formulations (LBFs) can be predicted from physicochemical properties. METHODS: Solubility was measured for 30 structurally diverse drug molecules in soybeanoil (SBO, long-chain triglyceride; TGLC), Captex355 (medium-chain triglyceride; TGMC), polysorbate 80 (PS80; surfactant) and PEG400 co-solvent and used as responses during PLS model development. Melting point and calculated molecular descriptors were used as variables and the PLS models were validated with test sets and permutation tests. RESULTS: Solvation capacity of SBO and Captex355 was equal on a mol per mol scale (R (2) = 0.98). A strong correlation was also found between PS80 and PEG400 (R (2) = 0.85), identifying the significant contribution of the ethoxylation for the solvation capacity of PS80. In silico models based on calculated descriptors were successfully developed for drug solubility in SBO (R (2) = 0.81, Q (2) = 0.76) and Captex355 (R (2) = 0.84, Q (2) = 0.80). However, solubility in PS80 and PEG400 were not possible to quantitatively predict from molecular structure. CONCLUSION: Solubility measured in one excipient can be used to predict solubility in another, herein exemplified with TGMC versus TGLC, and PS80 versus PEG400. We also show, for the first time, that solubility in TGMC and TGLC can be predicted from rapidly calculated molecular descriptors.
Authors: Aliya O Kasimova; Giovanni M Pavan; Andrea Danani; Karine Mondon; Andrea Cristiani; Leonardo Scapozza; Robert Gurny; Michael Möller Journal: J Phys Chem B Date: 2012-04-02 Impact factor: 2.991
Authors: Thao Do Thi; Michiel Van Speybroeck; Valery Barillaro; Johan Martens; Pieter Annaert; Patrick Augustijns; Jan Van Humbeeck; Jan Vermant; Guy Van den Mooter Journal: Eur J Pharm Sci Date: 2009-09-24 Impact factor: 4.384
Authors: Atanu Biswas; Brajendra K Sharma; J L Willett; Atanu Advaryu; S Z Erhan; H N Cheng Journal: J Agric Food Chem Date: 2008-06-18 Impact factor: 5.279
Authors: Matthew F Crum; Natalie L Trevaskis; Hywel D Williams; Colin W Pouton; Christopher J H Porter Journal: Pharm Res Date: 2015-12-24 Impact factor: 4.200
Authors: Jonas H Fagerberg; Eva Karlsson; Johan Ulander; Gunilla Hanisch; Christel A S Bergström Journal: Pharm Res Date: 2014-09-04 Impact factor: 4.200
Authors: Linda C Alskär; Janneke Keemink; Jenny Johannesson; Christopher J H Porter; Christel A S Bergström Journal: Mol Pharm Date: 2018-09-07 Impact factor: 4.939