Hot-melt extrusion of low and high moisture Kollidon® SR with sorbitol: Nanoindentation microhardness, creep deformation and powdered extrudate compression

Abstract

Kollidon® SR of low (KoL) or high (KoH) moisture content was hot-melt extruded with sorbitol (SOR). Microhardness of KoL/SOR and KoH/SOR extruded rods was determined by nanoindentation, and deformation by creep analysis. Compression of powdered extrudates was studied by instrumented tablet press. Interactions were examined by vibration spectroscopy, thermal changes by differential scanning calorimetry, and rod morphology by atomic force microscopy. High moisture KoH/SOR with low SOR (0%, 2.5%) exhibited high microhardness and low deformability of extruded rods, and also high yield pressure of compacted extrudate powders estimated from Heckel and Adams models. These effects were remarkably reversed at the 5% and 10% SOR, indicating plasticization of polymer. Anti-plasticizing action was noticed at 2.5% SOR in the microhardness of extruded rods and in the tensile strength of extrudate powder tablets. The influence of SOR on the properties of KoL/SOR extrudates was less pronounced, signifying the involvement of moisture in the plasticization of the polymer during HME. There is a linear correlation between rod microhardness and extrudate powder yield pressure (R²=0.792), and an excellent correlation with the tablet tensile strength (R²=0.986) indicating the importance of intrinsic material structure on compression. The above findings emphasize the need for proper storage of polymeric excipients.

Introduction

Hot-melt extrusion (HME) requires materials of suitable glass transition and low viscosity melt, which often necessitate the use of plasticizers. Kollidon® SR is used as a pH-independent sustain release matrix former and binder in conventional pharmaceutical processes such as direct compaction, granulation, and multiple dose unit formulations, as well as in more recent methodologies such as HME, 3D printing, and electrospinning (Mohylyuk and Davtian, 2015, Rahim et al., 2025, Seo et al., 2023, Zoubari et al., 2019). Its use in HME processing is advantageous due to its low Tg (42.5 °C) and high decomposition temperature (325.3 °C). Although it can be extruded alone, it is more efficiently processed with the addition of plasticizers (Wiranidchapong et al., 2015).

Sorbitol is a biodegradable, non-cariogenic polyol with sweet taste and mouth-cooling effect, making it a preferred diluent in pharmaceutical formulations (Cornick and Bowen, 1972, Dash et al., 2019, Rojas and Hernandez, 2014). Due to its high-water solubility, it is added in pellet matrices to facilitate dissolution (Goyanes and Martínez-Pacheco, 2015). While its use as a plasticizer in the food industry is well-known, it has also been employed in the HME processing of theophylline/starch (Chamarthy and Pinal, 2008). However, plasticization has not always been confirmed. Mikus et al. (Mikus et al., 2014) reported anti-plasticization for hot-melt extruded sorbitol/starch pellets at low polyol contents, and Róz et al. (Róz et al., 2006) reported anti-plasticization in thermally treated sorbitol/starch mixtures. Anti-plasticization is ascribed to entanglement of small polyol molecules between large polymer chains, thereby restricting chain mobility. which deteriorates processibility, mechanical properties, and dissolution.

Furthermore, the plasticizing action of water is well known and its effect on HME has been ascertained. Water has been found to assist HME processing of theophylline/starch (Chamarthy and Pinal, 2008) and the HME of Kollidon® SR/ibuprofen blends by mediating in the plasticization of Kollidon by the drug (Ozgüney et al., 2009). Conversely, Chamarthy and Pinal (Chamarthy and Pinal, 2008) reported that water interferes with the plasticizing action of sorbitol, showing inhibition at low water levels. Anti-plasticization of water at low levels has also been reported in co-amorphous systems (Xu et al., 2023, Xu et al., 2024). However, in the above studies, water was added to powdered HME feeds as liquid, by wet mixing. Consequently, the question arises whether moisture sorbed by hygroscopic polymers pre-exposed to high environmental humidity (RH) could impact on the plasticization of polymer by sorbitol, and moreover on the properties of the extruded product either as extruded rods, or compressed powder.

Therefore, in this work, the effect of sorbed moisture on Kollidon® SR, pre-exposed to low or high RH, on its plasticization by sorbitol during ΗΜΕ, and on the consequences on the mechanical properties of extruded rods and extrudate powder compaction was investigated. Solid-state changes with possible involvement of moisture were examined by spectroscopy and differential scanning calorimetry and extruded rod morphology was analyzed by atomic force microscopy. Rod microhardness was estimated from nanoindentation force-penetration (f/p) profiles, and creep deformation from indenter penetration-time profiles at constant indentation force. Compression data of powdered extrudates from ‘in-die’ force/displacement (f/d) were analyzed using Heckel’s and Adams’ compression models. Tensile strength of compressed tablets was measured by diametrical compression. Correlation of the results of nanoindentation measurements with compression parameters was attempted.

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Materials

Kollidon® SR polymer was a gift from BASF (Ludwigshafen, Germany) and sorbitol (Karion®) a gift from Merck (Darmstadt, Germany). Low moisture content (MC% = 2.57 ± 0.31) polymer (abbreviated KoL) was prepared by equilibration in desiccators over saturated K2CO3 solution (RH 43%), and high moisture content (MC% = 8.68 ± 0.88) polymer (abbreviated KoH) by equilibration over saturated NaCl solution (RH 75%). Sorbitol (abbreviated SOR) was stored in desiccators at RH 43%.

Ioannis Partheniadis, Miltiadis Toskas, Alexandros Karantzalis, Charikleia Prochaska, Ioannis Nikolakakis, Hot-melt extrusion of low and high moisture Kollidon® SR with sorbitol: Nanoindentation microhardness, creep deformation and powdered extrudate compression, Chemical Engineering Research and Design, Volume 228, 2026, Pages 535-547, ISSN 0263-8762, https://doi.org/10.1016/j.cherd.2026.03.026.

Read also our introduction article on Sorbitol here: