Investigation of Ethylene Oxide-co-propylene Oxide for Dissolution Enhancement of Hot-Melt Extruded Solid Dispersions

The Effect of Cooling on the Degree of Crystallinity, Solid-State Properties, and Dissolution Rate of Multi-Component Hot-Melt Extruded Solid Dispersions

“…The chemical structures of the materials used in this study are shown in Figure 1. Crystalline INM (1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-3-indoleacetic acid), purchased from Tokyo Chemical Industry (TCI) (Oxford Science Park, Oxford, UK) (N.V.) (Mw 357.79 g/mol −1 , Tm 160.0 °C Tg 42 °C) was used as the model drug [5]. INM has an aqueous solubility of 1.5 µg/ml at pH 1.2 [13].…”

“…INM has an aqueous solubility of 1.5 µg/ml at pH 1.2 [13]. P407, a hydrophilic non-ionic surfactant, (Mw 12,000, Tm 55 °C, Tg −67 °C) and PVP VA64 (Mw 45,000, Tg 107 °C, Tm 140 °C) was purchased from BASF Europe GmbH (Burgbernheim, Germany) [5]. PL-S630 (Mw 47,000, Tg 106 °C, Tm 140 °C) was received as a gift from Ashland Specialties Ltd, (UK) [6].…”

“…However, the application of high shear inherent to the process and high processing temperatures presents a significant challenge when dealing with APIs that are thermo-sensitive. However the inclusion of plasticizers as excipients can lower the processing temperatures associated with HME and can modify the physicochemical and dissolution properties of poorly water-soluble APIs [2,5]. Understanding the physicochemical properties of both the API and polymeric carriers is important when manufacturing SDs as it is the properties of the formulation that is being extruded that dictate the dissolution behaviour.…”

“…The results show that the dissolution rate of INM increased with increasing screw rotating speed or the mixer set temperature. Further research was carried out using semi-crystalline polymers such as Poloxamer 407 [P407] to overcome the drawbacks associated with HME such as its high processing temperatures [5,7], as the processing temperatures can restrict the proccesing of thermally labile drugs [8]. However, the cooling method used during the extrusion process can also have a significant effect on the crystallization tendency and solubility of the API.…”

“…INM has been used as a model drug in this study which is a BCS class II API (low solubility, high permeability). It is well reported in the literature that preparing an SD of INM significantly improved the amorphous stability and solubility of INM [5]. Poly(vinylpyrrolidone-co-vinyl acetate) [PVP VA64] and Plasdone-S630 [PL-S630] in terms of monographs, have the same chemical structure; however, they have different solid-state properties and solubilities depending on the manufacturing process used.…”