Date of Award
5-1-2026
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Dr. Mohammed Maniruzzaman
Second Advisor
Michael Repka
Third Advisor
Eman Ashour
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Lenalidomide, a cornerstone immunomodulatory drug for multiple myeloma and myelodysplastic syndromes, suffers from dissolution-rate-limited absorption and pronounced pharmacokinetic variability, limiting personalized dosing. This study developed a fully solvent-free cryomilling approach to prepare a 1:1 lenalidomide–nicotinamide (LND–NIC) cocrystal and integrated it into a hydrophilic polymeric matrix for semi-solid extrusion (SSE) 3D printing of personalized lattice tablets. The LND–NIC cocrystal was fabricated by cryomilling equimolar amounts of lenalidomide and nicotinamide for 45 min under liquid nitrogen. Successful cocrystal formation was confirmed by powder X-ray diffraction (new diagnostic peaks at 11.3°, 12°, and 23.3°), a single sharp DSC endotherm at 123.1 °C, and characteristic FTIR hydrogen-bonding shifts. The optimized cocrystal was incorporated at 35% w/w (48.12 mg lenalidomide per 200 mg tablet) into a PEG 6000/PEO N10 matrix with 0.2% fumed silica and printed via SSE at 75 °C using a BioX pneumatic printer. Comprehensive characterization demonstrated that the cocrystal phase was preserved during printing, with overall crystallinity of 66.8% (versus 68.4% for the physical mixture tablet) and retention of the 124.33 °C DSC peak. The printed tablets exhibited excellent mechanical properties (friability 0.33%, hardness 89.65–252.75 N) and acceptable content uniformity (90.84 ± 3.33% of theoretical, RSD 3.67%). Kinetic solubility studies in pH 7.2 phosphate buffer showed classic “spring-and-parachute” behavior for the cocrystal, with the 3D-printed tablet achieving the highest final concentration (0.57 mg/mL) while providing modulated early stage release. In vitro dissolution profiles were comparable across formulations (f? > 98.7). This work establishes a green, regulatory compliant platform that combines solvent free cocrystal engineering with point-of-care 3D printing, offering a viable strategy for personalized lenalidomide delivery with preserved solubility enhancement and improved processability. The approach has broad implications for overcoming dissolution limitations of high melting APIs in additive manufacturing.
Recommended Citation
Pawar, Kartik Vijay, "Solvent Free Fabrication of Lenalidomide Cocrystals and Their Integration into Printable Matrices for Personalized Pharmaceutical Tablets" (2026). Electronic Theses and Dissertations. 8863.
https://egrove.olemiss.edu/etd/8863