In Silico Screening for Solid Dispersions: The Trouble with Solubility Parameters and χFH

Molecular Pharmaceutics
Eleanor R TurpinMartin C Garnett

Abstract

The problem of predicting small molecule-polymer compatibility is relevant to many areas of chemistry and pharmaceutical science but particularly drug delivery. Computational methods based on Hildebrand and Hansen solubility parameters, and the estimation of the Flory-Huggins parameter, χ, have proliferated across the literature. Focusing on the need to develop amorphous solid dispersions to improve the bioavailability of poorly soluble drug candidates, an innovative, high-throughput 2D printing method has been employed to rapidly assess the compatibility of 54 drug-polymer pairings (nine drug compounds in six polymers). In this study, the first systematic assessment of the in silico methods for this application, neither the solubility parameter approach nor the calculated χ, correctly predicted drug-polymer compatibility. The theoretical limitations of the solubility parameter approach are discussed and used to explain why this approach is fundamentally unsuitable for predicting polymer-drug interactions. Examination of the original sources describing the method for calculating χ shows that only the enthalpic contributions to the term have been included, and the corrective entropic term is absent. The development and applicati...Continue Reading

References

Nov 17, 1999·Journal of Pharmaceutical Sciences·D J GreenhalghP York
Jun 7, 2000·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·C Leuner, J Dressman
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Oct 8, 2005·Journal of Computational Chemistry·Markus ChristenWilfred F van Gunsteren
Feb 21, 2009·Journal of Computational Chemistry·L MartínezJ M Martínez
May 16, 2009·Journal of Computational Chemistry·B R BrooksM Karplus
Jul 16, 2009·Current Pharmaceutical Design·Li DiGuy T Carter
Jun 4, 2010·Journal of the Royal Society, Interface·Samina AhmadIjeoma F Uchegbu
Jul 14, 2010·Journal of Pharmaceutical Sciences·Jared A BairdLynne S Taylor
Aug 24, 2010·International Journal of Pharmaceutics·Dexi Lin, Yanbin Huang
Feb 11, 2011·The Journal of Physical Chemistry. B·Jasmine GuptaSriramakamal Jonnalagadda
Jun 15, 2011·Nanomedicine : Nanotechnology, Biology, and Medicine·Loan HuynhChristine Allen
Mar 23, 2012·The Journal of Physical Chemistry. B·Aliya O KasimovaMichael Möller
Dec 25, 2012·International Journal of Pharmaceutics·Mohammed ManiruzzamanDennis Douroumis
Sep 24, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Chau Le-Ngoc VoBeom-Jin Lee
Apr 30, 1998·The Journal of Physical Chemistry. B·A D MacKerellM Karplus
Jul 12, 2014·Molecular Pharmaceutics·Amjad AlhalawehChristel A S Bergström
Mar 4, 2015·Molecular Pharmaceutics·Mohammed ManiruzzamanDennis Douroumis
Apr 29, 2015·Journal of Pharmaceutical Sciences·Tapan ParikhAbu T M Serajuddin
Jul 16, 2015·Journal of Pharmaceutical Sciences·Yan He, Chris Ho
Aug 4, 2015·Molecular Pharmaceutics·Katarzyna NurzyńskaPeter M Fischer
Nov 26, 2015·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Mahboobeh EslamiSeyed Abolfazl Seyed Sajadi
Jul 6, 2016·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Shrawan BaghelNiall J O'Reilly
Nov 11, 2016·Environmental Science and Pollution Research International·Milad Asgarpour KhansaryMehdi Asadollahzadeh
Dec 18, 2016·Journal of Pharmaceutical Sciences·Tian-Xiang Xiang, Bradley D Anderson
Jan 9, 2017·International Journal of Pharmaceutics·Paroma ChakravartyKarthik Nagapudi
Apr 9, 2017·Journal of Pharmaceutical Sciences·Kevin DeBoyace, Peter L D Wildfong

❮ Previous
Next ❯

Citations

Mar 23, 2019·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Jinwen QinMinhua Cao
Jan 7, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniel M WaldenJyotika Varshney
Jul 4, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Zhengwei HuangChuanbin Wu
May 28, 2021·Molecular Pharmaceutics·Samarth D ThakoreArvind K Bansal
Apr 30, 2020·Molecular Pharmaceutics·Rashidat K AnimasawunMartin C Garnett

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.