Driving innovation in pharmaceuticals: integrated studies of physical dissolution properties of crystalline and amorphous forms using enhanced orthogonal monitoring techniques.
Aim of CRYDIS
CRYDIS undertakes innovative, collaborative research on the clinically-important topic of dissolution of drug substance particles in bio-relevant media and the undesired subsequent nucleation and re-precipitation of the drug prior to its absorption.
Using innovative advances in UV imaging technology, CRYDIS investigates the utility of novel dissolution assays as key tools to obtain fundamental data on the mechanism and kinetics of undesired nucleation and re-precipitation during or following dissolution, a significant problem for the pharmaceutical industry which struggles to obtain sufficient exposure to poorly soluble drug substances to ensure an effective dose is absorbed by the patient.
The key technologies in this project offer a step change in capability and functionality, offering the potential to undertake more detailed studies of the dissolution/re-precipitation processes relevant to pharmaceutical materials. Access to this key technology and the further development of its capability offers the potential for breakthroughs in development of process understanding and of robust and widely applicable protocols, thus, on a longer term perspective contributing to faster translation of molecules to medicines to patients.
- Paraytec Ltd, York, UK
- Pfizer Ltd, Sandwich, UK
- Sirius Analytical Ltd, Forest Row, UK
- University College Cork, Cork, Ireland
- University of Copenhagen, Copenhagen, Denmark
CRYDIS is a Marie Skłodowska-Curie Research and Innovation Staff Exchange (RISE) project under the European Union´s Horizon 2020 programme running from January 2015 through December 2017. The CRYDIS exchange programme will establish and support international and inter-sectoral transfer of knowledge and expertise in pharmaceutical and instrument science between several EU research institutes and industrial companies. The project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 644056.
For further information please contact project coordinator Associate Professor Jesper Østergaard, Department of Pharmacy, University of Copenhagen, e-mail: firstname.lastname@example.org.
High information content analytical methods for assessing drug dissolution and precipitation using UV imaging and orthogonal techniques are developed.
A robust, simultaneous UV imaging and Raman microscopy approach have been established for visualizing the dissolution process and monitoring solid form changes occurring during dissolution.
An approach for local pH measurements in the immediate vicinity of the drug solid surface (in situ pH imaging) has been established using the UV-Vis imaging platform that demonstrates potential for assessment of dissolution related pH changes.
Proof-of-concept studies demonstrate the feasibility of measuring drug supersaturation, precipitation and dissolution using UV-Vis imaging in combination with light microscopy and Raman spectroscopy.
Recent advances in UV-Vis imaging instrumentation facilitating dual-wavelength imaging have been utilized in development of methods for characterization of multi-component systems, e.g., drug excipient mixtures.
The novel analytical capabilities within UV imaging/surface dissolution imaging are exploited to conduct detailed dissolution characterization of drug substances subject to form transformation, including anhydrate to hydrate conversion and salt disproportionation.
The suitability of UV-Vis imaging for characterization of multicomponent systems, such as cocrystals and drug-polymer matrixes has been demonstrated.
In situ UV metric assays have been applied to assess the performance of cocrystals.
Whole tablet imaging utilizing the Sirius SDi2 UV-Vis imaging platform has documented the potential with respect to identifying dissolution and precipitation phenomena for whole dosage forms under biorelevant conditions.
Controlled supersaturation and precipitation experiments have been undertaken for assessment for induction times and precipitation rates in relation to the degree of supersaturation.
One focus is on the translation of nucleation models in bio-relevant media. To this end, the role of the components of the intestinal fluids in inhibiting nucleation and drug precipitation is currently under investigation.
Activities and Output
Application of UV imaging in formulation development.
Sun, Yu; Østergaard, Jesper.
I: Pharmaceutical Research, Bind 34, Nr. 5, 2017, s. 929–940.
Performance characteristics of UV imaging instrumentation for diffusion, dissolution and release testing studies.
Jensen, Sabrine S; Jensen, Henrik; Goodall, David M; Østergaard, Jesper.
In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 131, 30.11.2016, p. 113-123.
Surface Dissolution Imaging Workshop: Introduction to UV imaging for drug dissolution and release testing.
June 8-10, 2015. Department of Pharmacy, University of Copenhagen