Approaches to increase mechanistic understanding and aid in the selection of precipitation inhibitors for supersaturating formulations - a PEARRL review.
- Price DJ Merck KGaA, Darmstadt, Germany.
- Ditzinger F Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
- Koehl NJ School of Pharmacy, University College Cork, Cork, Ireland.
- Jankovic S Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
- Tsakiridou G Pharmathen SA, Product Design & Evaluation, Athens, Greece.
- Nair A Merck KGaA, Darmstadt, Germany.
- Holm R Drug Product Development, Janssen Research and Development, Johnson and Johnson, Beerse, Belgium.
- Kuentz M Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland.
- Dressman JB Frankfurt Goethe University, Frankfurt, Germany.
- Saal C Merck KGaA, Darmstadt, Germany.
- 2018-05-18
Published in:
- The Journal of pharmacy and pharmacology. - 2019
controlled and sustained release systems
development of novel analytical techniques
dosage form design and characterisation
pharmaceutical analysis
pharmaceutics and drug delivery
Chemical Precipitation
Chemistry, Pharmaceutical
Drug Compounding
Drug Delivery Systems
Humans
Models, Molecular
Pharmaceutical Preparations
Solubility
Technology, Pharmaceutical
English
OBJECTIVES
Supersaturating formulations hold great promise for delivery of poorly soluble active pharmaceutical ingredients (APIs). To profit from supersaturating formulations, precipitation is hindered with precipitation inhibitors (PIs), maintaining drug concentrations for as long as possible. This review provides a brief overview of supersaturation and precipitation, focusing on precipitation inhibition. Trial-and-error PI selection will be examined alongside established PI screening techniques. Primarily, however, this review will focus on recent advances that utilise advanced analytical techniques to increase mechanistic understanding of PI action and systematic PI selection.
KEY FINDINGS
Advances in mechanistic understanding have been made possible by the use of analytical tools such as spectroscopy, microscopy and mathematical and molecular modelling, which have been reviewed herein. Using these techniques, PI selection can be guided by molecular rationale. However, more work is required to see widespread application of such an approach for PI selection.
SUMMARY
Precipitation inhibitors are becoming increasingly important in enabling formulations. Trial-and-error approaches have seen success thus far. However, it is essential to learn more about the mode of action of PIs if the most optimal formulations are to be realised. Robust analytical tools, and the knowledge of where and how they can be applied, will be essential in this endeavour.
Supersaturating formulations hold great promise for delivery of poorly soluble active pharmaceutical ingredients (APIs). To profit from supersaturating formulations, precipitation is hindered with precipitation inhibitors (PIs), maintaining drug concentrations for as long as possible. This review provides a brief overview of supersaturation and precipitation, focusing on precipitation inhibition. Trial-and-error PI selection will be examined alongside established PI screening techniques. Primarily, however, this review will focus on recent advances that utilise advanced analytical techniques to increase mechanistic understanding of PI action and systematic PI selection.
KEY FINDINGS
Advances in mechanistic understanding have been made possible by the use of analytical tools such as spectroscopy, microscopy and mathematical and molecular modelling, which have been reviewed herein. Using these techniques, PI selection can be guided by molecular rationale. However, more work is required to see widespread application of such an approach for PI selection.
SUMMARY
Precipitation inhibitors are becoming increasingly important in enabling formulations. Trial-and-error approaches have seen success thus far. However, it is essential to learn more about the mode of action of PIs if the most optimal formulations are to be realised. Robust analytical tools, and the knowledge of where and how they can be applied, will be essential in this endeavour.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1111/jphp.12927
- PMID 29770440
- Persistent URL
- https://sonar.ch/global/documents/92606
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