Theoretical modeling and mechanism of drug release from controlled release implants by microstructural image characterization
AssigneeMerck Sharp & Dohme Corp.
InventorsRoberto Irizarry, Antong Chen, Daniel Skomski
Life of this patent
Estimating the term…
Abstract
Embodiments disclosed herein relate to a model for predicting the release profile of a controlled release device. The implant modeling system and models disclosed herein allow the accurate prediction of a release profile for a controlled release device based on features extracted from micro-resolution imagery. The models combine microstructural features that can be extracted at the XRCT resolution, including pore volume and connectivity, using erosion-dilation image analysis. This strategy allows prediction of release curves of the controlled release device using XRCT despite its resolution limitations.
Claims20
A computer-implemented method for estimating a release profile of a device for releasing a compound, the method comprising:
- receiving an x-ray computed tomography (XRCT) image of the device, the device comprising particles of the compound embedded in a plurality of pores in a matrix;
- generating an unlabeled mask from the XRCT image, the unlabeled mask identifying pores and necks connecting a set of the pores;
- performing an erosion process on the unlabeled mask to generate an eroded mask, the erosion process eroding the pores and removing the necks connecting the set of the pores resulting in disconnected pores;
- labeling the disconnected pores in the eroded mask;
- performing a dilation process on the eroded mask to generate a dilated mask, the dilation process enlarging the labeled pores that were previously eroded and unlabeled;
- extracting, from the dilated mask, a set of features including pore volumes and connectivities for the labeled pores;
- retrieving a minimalistic model for estimating the release profile of the device based on the pore volume and connectivity, wherein the minimalistic model determines a correlation between a release coefficient for a Higuchi-type release and an XRCT parameter, wherein the XRCT parameter is based on the pore volumes and connectivities;
- and estimating the release profile of the device based on the correlation determined using the retrieved minimalistic model and the pore volumes and connectivities.
A system for estimating a release profile of a device for releasing a compound, the system comprising:
- an x-ray computed tomography (XRCT) imaging system configured to capture an XRCT image of the device, the device comprising particles of the compound embedded in a plurality of pores in a matrix;
- at least one processor;
- and a non-transitory computer readable medium comprising stored instructions, the instructions when executed by the at least one processor cause the at least one processor to:
- generate an unlabeled mask from the XRCT image, the unlabeled mask identifying pores and necks connecting a set of the pores;
- perform an erosion process on the unlabeled mask to generate an eroded mask, the erosion process eroding the pores and removing the necks connecting the set of the pores resulting in disconnected pores;
- label the disconnected pores in the eroded mask;
- perform a dilation process on the eroded mask to generate a dilated mask, the dilation process enlarging the labeled pores that were previously eroded and unlabeled;
- extract, from the dilated mask, a set of features including pore volumes and connectivities for the labeled pores;
- retrieve a minimalistic model for estimating the release profile of the device based on the pore volume and connectivity, wherein the minimalistic model determines a correlation between a release coefficient for a Higuchi-type release and an XRCT parameter, wherein the XRCT parameter is based on the pore volumes and connectivities;
- and estimate the release profile of the device based on the correlation determined using the retrieved minimalistic model and the pore volumes and connectivities.
A non-transitory computer-readable medium comprising instructions for estimating a release profile of a device for releasing a compound, the instructions, when executed by a computing system, causing the computing system to perform operations including:
- receiving an x-ray computed tomography (XRCT) image of the device, the device comprising particles of the compound embedded in a plurality of pores in a matrix;
- generating an unlabeled mask from the XRCT image, the unlabeled mask identifying pores and necks connecting a set of the pores;
- performing an erosion process on the unlabeled mask to generate an eroded mask, the erosion process eroding the pores and removing the necks connecting the set of the pores resulting in disconnected pores;
- labeling the disconnected pores in the eroded mask;
- performing a dilation process on the eroded mask to generate a dilated mask, the dilation process enlarging the labeled pores that were previously eroded and unlabeled;
- extracting, from the dilated mask, a set of features including pore volumes and connectivities for the labeled pores;
- retrieving a minimalistic model for estimating the release profile of the device based on the pore volume and connectivity, wherein the minimalistic model determines a correlation between a release coefficient for a Higuchi-type release and an XRCT parameter, wherein the XRCT parameter is based on the pore volumes and connectivities;
- and estimating the release profile of the device based on the correlation determined using the retrieved minimalistic model and the pore volumes and connectivities.
Dependencies are inferred from the claim text.