Strategies to Address Low Drug Solubility in Discovery and Development

@article{Williams2013StrategiesTA,
  title={Strategies to Address Low Drug Solubility in Discovery and Development},
  author={Hywel D Williams and Natalie L. Trevaskis and Susan A. Charman and Ravi Mysore Shanker and William N. Charman and Colin W. Pouton and Christopher J. H. Porter},
  journal={Pharmacological Reviews},
  year={2013},
  volume={65},
  pages={315 - 499}
}
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… Expand
Polymorph Impact on the Bioavailability and Stability of Poorly Soluble Drugs
TLDR
The concepts involved, examples of drugs characterized by poor solubility for which polymorphism has proven important, outlines the state-of-the-art technologies and discusses the pertinent regulations. Expand
Support Tools in Formulation Development for Poorly Soluble Drugs.
TLDR
This review aims to list available support tools and explain how they are used and try to predict which route will best suit the API based on selected molecular parameters such as molecular weight, lipophilicity, and solubility. Expand
Editorial: Persistent endeavors for the enhancement of dissolution and oral bioavailability
TLDR
This special issue brings together prominent scientists to showcase the most recent advances in the big field of enhancement of dissolution and oral bioavailability, as research interest has shifted towards understanding of the performance of drug crystals, especially nanocry crystals, both in vitro and in vivo, as well as development of new methods for efficient production of nanocrystals and cocrystals. Expand
From Molecule to Dose Form – Accelerated Bioavailability Enhancement for Early Phase Molecules
Water solubility is a key parameter in drug formulation since it highly influences drug pharmacokinetics and pharmacodynamics. In the past decades, the challenge with poorly water soluble drugs hasExpand
Solubility and dissolution enhancement strategies: current understanding and recent trends*
Abstract Identification of lead compounds with higher molecular weight and lower aqueous solubility has become increasingly prevalent with the advent of high throughput screening. Poor aqueousExpand
Identification of solubility-limited absorption of oral anticancer drugs using PBPK modeling based on rat PK and its relevance to human.
TLDR
Ten anticancer drugs that exhibit poor in vitro solubility were selected and oral rat pharmacokinetic studies were performed at the body weight-scaled doses of the model drugs' human food effect studies, and the findings were analyzed using a top-down PBPK modeling approach. Expand
Optimizing Oral Bioavailability in Drug Discovery: An Overview of Design and Testing Strategies and Formulation Options.
  • B. Aungst
  • Medicine
  • Journal of pharmaceutical sciences
  • 2017
TLDR
The bioavailability challenges currently faced in drug discovery are summarized, and the design and testing methods and strategies currently utilized to address the challenges are summarized. Expand
Strategies for formulating and delivering poorly water-soluble drugs
TLDR
The present article presents and discusses the pharmaceutical strategies available to overcome poor water solubility in light of final drug product examples and physical modifications based on modified solid states of the drug, small drug particles, cosolvents, surfactants, lipids and cyclodextrins. Expand
Use of biorelevant dissolution and PBPK modeling to predict oral drug absorption
  • N. Kaur, A. Narang, A. Bansal
  • Chemistry, Medicine
  • European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
  • 2018
TLDR
The evolution, present status, and future trends on the applicability of biorelevant in vitro dissolution testing and in silico modeling for predicting oral absorption and pharmacokinetics of poorly soluble weakly basic drugs are discussed. Expand
A practical approach to modeling the impact of amorphous drug nanoparticles on the oral absorption of poorly soluble drugs.
TLDR
The nano-modified permeability method can be a suitable, fit-for-purpose in silico approach for evaluating or predicting oral absorption of poorly soluble, UWL-limited drugs from formulations that produce a significant number of amorphous drug nanoparticles. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 1,666 REFERENCES
Improvement in aqueous solubility in small molecule drug discovery programs by disruption of molecular planarity and symmetry.
TLDR
Aqueous solubility is essential for drug candidates and application of combinatorial chemistry and highthroughput screening (HTS) systems has tended to change the profile of compound libraries in the direction of greater hydrophobicity and higher molecular weight, and this in turn has resulted in a profile of lowersolubility. Expand
Prodrug strategies to overcome poor water solubility.
TLDR
This review explores the use of pro drug interventions to effect improved oral and parenteral delivery of poorly water-soluble problematic drugs, using both marketed as well as investigational prodrugs as examples. Expand
Selection of oral bioavailability enhancing formulations during drug discovery
TLDR
A thorough understanding of not only the formulation technique but also the physical form of research compounds is critical to ensure physical stability, successful pharmacokinetic (PK) profiling and early developability risk assessment. Expand
Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability?
TLDR
Methods and excipients associated with the development of supersaturating drug delivery systems are assessed and the future directions and factors likely to contribute to or detract from optimal dosage form selection are assessed. Expand
Injectable Formulations of Poorly Water-Soluble Drugs
A growing number of new therapeutic molecules are limited by low or erratic bioavailability due to poor water solubility. Because of the clinical demand for new and more efficacious anti-cancer,Expand
Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system.
  • C. Pouton
  • Chemistry, Medicine
  • European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2006
TLDR
The use of a lipid formulation classification system combined with appropriate in vitro tests will help to establish a database for in vitro-in vivo correlation studies and improve the understanding of the factors which affect drug crystallization. Expand
Recent advances in intravenous delivery of poorly water-soluble compounds
TLDR
An overview of the recent advances in formulation approaches and drug delivery technologies for poorly water-soluble compounds applicable to i.v. administration for oncology and anesthesia is provided. Expand
Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates.
TLDR
The concept and theory of crystal engineering is covered and the potential benefits, disadvantages and methods of preparation of co-crystals, metastable polymorphs, high-energy amorphous forms and ultrafine particles are discussed. Expand
Amorphous Active Pharmaceutical Ingredients in Preclinical Studies: Preparation, Characterization, and Formulation
Abstract: A large number of the new pharmaceutical small molecules under development today are found to have poor water solubility. This in turn may lead to low bioavailability, which can have aExpand
Intravenous administration of poorly soluble new drug entities in early drug discovery: the potential impact of formulation on pharmacokinetic parameters.
TLDR
Provided the analytical technique used to determine drug concentration in the body is sensitive enough to allow compound administration at low doses, screening formulations at comparatively low concentrations may be feasible. Expand
...
1
2
3
4
5
...