Developing and combining techniques:
High information content analytical methods for assessing drug dissolution and precipitation using UV imaging and orthogonal techniques have been developed.
A robust, simultaneous UV imaging and Raman spectroscopy approach have been established for visualizing the dissolution process and monitoring solid form changes occurring during dissolution. A step-by-step guideline for dissolution imaging studies with in situ Raman spectroscopy was developed.
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 pH changes.
Proof-of-concept studies demonstrated 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.
An interlab study using the first generation SDI system for assessing intrinsic dissolution rates of 6 drug substances addressed the extent of variability associated with the method upon development of a common protocol. Overall, the rank ordering was as expected and the variability associated with the measurements was related to the solubility of the compounds.
Studying the dissolution and precipitation of pharmaceutical materials:
The novel analytical capabilities within UV imaging/surface dissolution imaging have been 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 used to assess the performance of cocrystals.
Whole tablet imaging utilizing the Sirius SDi2 UV-Vis imaging platform has shown the potential with respect to identifying dissolution and precipitation phenomena for whole dosage forms under biorelevant conditions.
Fundamentals of nucleation processes relevant to dissolution phenomena:
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 has been investigated and components responsible for both the inhibition and the promotion of nucleation have been identified.
