Challenging pharmaceutical development problems require innovative solutions. At DigiM Solution, we believe that microstructures are at the core of engineering and optimizing drug product performance. With our advanced AI analytics and image-based simulations, we have helped clients accelerate formulation, process development, performance troubleshooting, and more. We were honored to exhibit and present this work at 2022 AAPS PharmSci360 conference.
3D XRM microstructural imaging of a Claritin-D12 tablet. Left half is the segmented dataset while the right is the original image.
Presented by DigiM Solution
Using Claritin 12-hour formulation as an example, we demonstrate how XRM and MFV-SEM analysis can quantify the complex microstructure and spatial arrangement of oral solid dosage forms. From macroscale observation of coating layers to highly magnified nanoscale observation of individual ingredients, MVF-SEM can be used as a critical imaging technique to inform formulation decisions. 3D XRM was also applied to study the structures of Claritin non-invasively, and AI segmentation was applied to quantify domain size and distribution from these images. For generic product development, these techniques can be applied towards formulation optimization, quality control and assurance, microstructure bioequivalence, forensic analysis, reverse engineering, stability assessment, and regulatory support.
Data points from in vitro and in vivo release testing (dots) and the simulated release models (lines) developed from imaged datasets.
Presented by DigiM Solution with Innocore
Purpose: To better address the needs for contraception, especially in low- and middle-income countries, novel biodegradable contraceptive implants are developed using a bioresorbable multi-block copolymer platform. The formulation and performance assessment of such long-acting implants are outstanding challenges due to the extended timescale traditionally required for release testing. In this project, long-acting implants formulated with multi-block copolymers are investigated using an innovative image-based approach to assess microstructure characteristics of the implants during release testing. Release performance is also simulated using the imaging data allowing for rapid assessment of implant performance in days as opposed to months and years with traditional release testing.
Ultra-high magnification zoom-in on a region of the core tablet and the corresponding segmentation for (a) Claritin-D 12 and (b) CVS Allergy Relief-D12.
Presented by DigiM Solution
Purpose: Given their complex nature, modified release systems demand an unprecedented understanding of the microstructure and ingredient distribution fundamental to product performance and quality. From coatings to multiple layers to a large number of ingredients, complex oral dosage forms are especially intricate. It is therefore fundamental to quantify critical quality attributes that can be optimized for ideal product performance and quality. Coated bilayer sustained release oral dosage compositions containing a nasal decongestant and an antihistamine were selected as a model formulation. The objective of this work was to visualize and quantify the foundational microstructure of these modified release tablets with the application of high-resolution imaging, correlative spectroscopy, and cutting-edge artificial intelligence(AI)-based image analytics.
3D XRM images showcasing the microstructure morphology and corresponding segmentation for dispersion particles. Interparticle air are highlighted by the blue arrow, solids by bright green arrow, and porosity by red arrow.
Presented by Dr. Hao Helen Hou from Genentech with DigiM
Purpose: Formulating poorly water-soluble compounds as amorphous solid dispersions (ASDs) is one of the most promising approaches to enhance solubility and/or dissolution, and membrane flux to improve bioavailability. Due to the unstable nature of amorphous materials and the underlying principle for their formation, it is clear that the manufacturing technology and process conditions would impact ASD material characteristics and properties, and in turn in vivo performance. The purpose of this work is to evaluate the interrelationship of microstructure, properties, and dissolution performance for ASDs prepared using different methods.
Presented by Ruifeng Wang from UCONN with the FDA and DigiM
Purpose: Minor changes in the manufacturing processes are shown to affect physicochemical properties (such as particle size, and morphology) as well as the drug release behavior of microspheres. To model these changes, minocycline HCl was selected to investigate the effect of coacervation processing parameters on PLGA microsphere quality and in vitro release characteristics.
(a) In vitro release of meloxicam from PCL matrices with varying amounts of Mg(OH)2. (b) XRM digital reconstruction of implants before drug
release with 20 (i), 35 (ii), and 50 (iii) % of Mg(OH)2.
Presented by Dr. Yun-Chu Chen from Purdue with DigiM
Purpose: Anti-inflammatory drugs can reduce inflammatory responses following surgery and prevent biofouling of implantable devices. Controlling the kinetics of drug release is critical because excessive anti-inflammatory drugs may interfere with wound healing. For preventing the development of chronic inflammation, 14 days are known to be the optimal duration. Meloxicam release can be controlled by adjusting the drug content in a polymer matrix; however, when the geometry and dose are dictated by the size of surgical wound or the dimension of implants, there is little room for adjusting the drug content. Therefore, we aim to develop a formulation strategy to facilitate sustained/controlled meloxicam release given the constraints in geometry and dose.