PMID: 23383426Feb 7, 2013Paper

Strategies to address low drug solubility in discovery and development

Pharmacological Reviews
Hywel D WilliamsChristopher J H Porter


Drugs with low water solubility are predisposed to low and variable oral bioavailability and, therefore, to variability in clinical response. Despite significant efforts to "design in" acceptable developability properties (including aqueous solubility) during lead optimization, approximately 40% of currently marketed compounds and most current drug development candidates remain poorly water-soluble. The fact that so many drug candidates of this type are advanced into development and clinical assessment is testament to an increasingly sophisticated understanding of the approaches that can be taken to promote apparent solubility in the gastrointestinal tract and to support drug exposure after oral administration. Here we provide a detailed commentary on the major challenges to the progression of a poorly water-soluble lead or development candidate and review the approaches and strategies that can be taken to facilitate compound progression. In particular, we address the fundamental principles that underpin the use of strategies, including pH adjustment and salt-form selection, polymorphs, cocrystals, cosolvents, surfactants, cyclodextrins, particle size reduction, amorphous solid dispersions, and lipid-based formulations. In each...Continue Reading


May 1, 1976·Archives of Ophthalmology·L G Carney, R M Hill
Nov 1, 1976·Journal of Pharmaceutical Sciences·A LongwellD Moore
Sep 1, 1978·Journal of Pharmaceutical Sciences·Z T Chowhan
Feb 1, 1979·Journal of Pharmaceutical Sciences·J B Bogardus, R K Blackwood
Dec 1, 1979·The Journal of Pharmacy and Pharmacology·B J HargreavesP Connor
May 1, 1977·Chemical & Pharmaceutical Bulletin·K IkedaT Yotsuyanagi
Mar 1, 1976·Journal of Pharmaceutical Sciences·D C Bloedow, W L Hayton
Oct 1, 1976·Food and Cosmetics Toxicology·T F Ferguson, C Prottey
Apr 13, 1979·Science·J S Patton, M C Carey
Sep 1, 1979·Journal of Pharmaceutical Sciences·G L FlynnA F Hofmann
Jan 1, 1977·Journal of Pharmaceutical Sciences·S HannaL Lachman
Feb 1, 1978·Journal of Pharmaceutical Sciences·C A HirschJ L Brannon
Jan 1, 1977·Journal of Pharmaceutical Sciences·S M BergeD C Monkhouse
Nov 1, 1976·Journal of Pharmaceutical Sciences·M P Summers, R P Enever
Apr 1, 1975·Journal of Pharmaceutical Sciences·H Schott, S K Han
Jan 1, 1992·The Journal of Pharmacy and Pharmacology·H Viernstein, C Stumpf
Oct 1, 1992·Clinical Pharmacokinetics·R JanknegtD J Crommelin
Dec 1, 1992·Journal of Pharmaceutical Sciences·K R MorrisA T Serajuddin
Jul 1, 1992·British Journal of Cancer·D M WoodcockW H Sawyer
Sep 1, 1991·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·E K RowinskyR C Donehower
Dec 1, 1991·Journal of Pharmaceutical Sciences·G BettinettiF Giordano
Jul 11, 1990·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R B WeissB Leyland-Jones
Mar 1, 1991·Pharmaceutical Research·H W FrijlinkD K Meijer
Jul 9, 1990·Biochimica Et Biophysica Acta·M N OrsenigoA Faelli

❮ Previous
Next ❯


Feb 23, 2013·Pharmaceutical Research·Natalie L TrevaskisChristopher J H Porter
Oct 26, 2013·Pharmaceutical Research·Christopher J H PorterNatalie L Trevaskis
May 21, 2013·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Ravi DevrajColin W Pouton
Jun 4, 2013·International Journal of Pharmaceutics·Irena TomaszewskaNikoletta Fotaki
Jan 7, 2014·Chemical & Pharmaceutical Bulletin·Atsushi Fujihira, Nobuaki Shimizu
Aug 28, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Sarala YanamandraGuru V Betageri
Jul 25, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Orlagh M FeeneyChristopher J H Porter
Jul 23, 2013·International Journal of Pharmaceutics·T T H PhamG Barratt
Aug 26, 2014·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Claire L McEvoyChristopher J H Porter
Feb 16, 2016·Molecular Pharmaceutics·Fengjuan CaoGregory E Amidon
Jan 31, 2016·International Journal of Pharmaceutics·Joaquim J Moura Ramos, Hermínio P Diogo
Feb 9, 2016·Journal of Pharmaceutical and Biomedical Analysis·Baiwei Lin, Joseph H Pease
Dec 30, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Meysam MobasheriMahmoud Reza Jaafari
Oct 27, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Roberta Censi, Piera Di Martino
Aug 5, 2014·Marine Drugs·Alessandra Mirtes Marques Neves GonçalvesGustavo Henrique Ribeiro Viana
Jan 6, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daniela Hartmann JornadaMan Chin Chung
May 12, 2015·Expert Opinion on Drug Delivery·Federica Leone, Roberta Cavalli
Feb 20, 2014·Expert Opinion on Drug Delivery·Mauro Magnani, Luigia Rossi
Sep 11, 2014·Drug Development and Industrial Pharmacy·Yanghuan YeBaojian Wu
Oct 25, 2014·Drug Development and Industrial Pharmacy·Shashank JainSenshang Lin
May 21, 2013·Expert Opinion on Drug Delivery·Sergei G Kazarian, Andrew V Ewing
Feb 2, 2016·Advanced Drug Delivery Reviews·José das NevesBruno Sarmento
Feb 12, 2014·Journal of Pharmaceutical Sciences·Cordula StillhartMartin Kuentz
Jun 20, 2015·Journal of Pharmaceutical Sciences·Peng ZhangMaria Strømme
Jun 23, 2015·Journal of Pharmaceutical Sciences·Fatemeh KeramatniaAbolghasem Jouyban
May 23, 2013·Journal of Pharmaceutical Sciences·Suzanne M CaliphNatalie L Trevaskis
Sep 27, 2014·Journal of Pharmaceutical Sciences·Arzu SelenJennifer B Dressman
Mar 31, 2015·Journal of Pharmaceutical Sciences·Sharad B MurdandeRutesh H Dave
Jul 6, 2014·Journal of Pharmaceutical Sciences·Hywel D WilliamsUNKNOWN Communicated on Behalf of the LFCS Consortium
Oct 28, 2015·Journal of Pharmaceutical Sciences·Bart HensPatrick Augustijns
Jul 16, 2015·Journal of Pharmaceutical Sciences·Yan He, Chris Ho
Feb 3, 2016·Advanced Drug Delivery Reviews·Paul D Leeson

❮ Previous
Next ❯

Related Concepts

Trending Feeds


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 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.


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.