The impact of the injection mold temperature upon polymer crystallization and resulting drug release from immediate and sustained release tablets

Abstract

It was the aim of this study to elucidate the impact of the injection mold temperature upon the polymer crystallinity, its microstructure and the resulting drug release from immediate and sustained release tablets containing semi-crystalline polymers. The immediate release formulation contained 20% (w/w) ketoprofen (KETO) in poly (ethylene oxide) (PEO) and the sustained release formulation contained 20-40% (w/w) metoprolol tartrate (MPT) in polycaprolactone (PCL). Physical mixtures of drug-polymer were characterized via isothermal crystallization experiments using DSC and rheological measurements to elucidate the impact of the drug solid-state upon the crystallization kinetics. Tablets were prepared using various thermal histories (extrusion barrel temperature and injection mold temperatures). Polymer crystallinity and microstructure in the tablets was characterized via DSC and polarized optical microscopy. The polymer microstructure was altered by the various applied thermal histories. The differences in PEO crystallinity induced by the various mold temperatures did not affect the KETO dissolution from the tablets. On the other hand, MPT (20-40% w/w) dissolution from the PCL matrix when extruded at 80 °C and injection molded at 25 and 35 °C was significantly different due to the changes in the polymer microstructure. More perfect polymer crystals are obtained with higher mold temperatures, decreasing the drug diffusion rate through the PCL matrix. The results presented in this study imply that the injection mold temperature should be carefully controlled for sustained release formulations containing hydrophobic semi-crystalline polymers.

Investigation on the use of fused deposition modeling for the production of IR dosage forms containing Timapiprant

“…The manufacturing of products meeting the desired dissolution specification ( i.e. t 80% ≤ 30 min) via extrusion-based hot-processing techniques would be particularly challenging, because these are well-known to provide high density products characterized by slow penetration of aqueous fluids [ Casati et al, 2020 ; Fuenmayor et al, 2019 ; Tanaka et al, 2021 ; Van Renterghem et al, 2018 ; Verstraete et al, 2016 ; Zema et al, 2012 ]. A screening program for the identification of thermoplastic carriers suitable for FDM of solid units having a dissolution performance comparable to that of reference tablets was undertaken, taking into account a variety of polymers already deemed suitable for hot-processing [ Hardung et al, 2010 ; Melocchi et al, 2016 ; Nunes et al, 2022 , Tanno et al, 2004 ].…”

The factors influencing the efficiency of drug-coated balloons

“…vasculature (59,60). Current studies of temperature have been limited to the radiofrequency ablation of atherosclerotic plaques using balloon temperature, such as the PLOSA balloon catheter, which melts plaque by transferring heat to the vascular wall (61)(62)(63).…”

“…Recent studies have shown that temperature could be considered another important factor. Temperature not only changes the solubility of lipophilic antiproliferative drugs and thus affects drug release, but it also promotes the transfer of drug molecules into the deeper vasculature ( 59 , 60 ). Current studies of temperature have been limited to the radiofrequency ablation of atherosclerotic plaques using balloon temperature, such as the PLOSA balloon catheter, which melts plaque by transferring heat to the vascular wall ( 61 – 63 ).…”

Nanostructured Composites of Sodium Montmorillonite Clay and PEO Used in Dissolution Improvement of Aprepitant Drug by Melt Mixing

“…This was expected since melt mixing was taking place at a lower temperature than the melting point of the drug, in order to avoid drug decomposition. Also, this is very common when semicrystalline polymers are used for the preparation of drug solid dispersions [66][67][68]. This is ought to improve polymer microstructure and especially that of existing polymer crystal which acts as a nucleating agent for drug crystallization.…”