Investigation of Thermal and Viscoelastic Properties of Polymers Relevant to Hot Melt Extrusion, IV: Affinisol™ HPMC HME Polymers

Abstract

Abstract. Most cellulosic polymers cannot be used as carriers for preparing solid dispersion of drugs by hot melt extrusion (HME) due to their high melt viscosity and thermal degradation at high processing temperatures. Three HME-grade hydroxypropyl methylcelluloses, namely Affinisol™ HPMC HME 15 cP, Affinisol™ HPMC HME 100 cP, and Affinisol™ HPMC HME 4 M, have recently been introduced by The Dow Chemical Co. to enable the preparation of solid dispersion at lower and more acceptable processing temperatures. In the present investigation, physicochemical properties of the new polymers relevant to HME were determined and compared with that of Kollidon ® VA 64. Powder X-ray diffraction (PXRD), modulated differential scanning calorimetry (mDSC), thermogravimetric analysis (TGA), moisture sorption, rheology, and torque analysis by melt extrusion were applied. PXRD and mDSC showed that the Affinisol™ polymers were amorphous in nature. According to TGA, the onset of degradation for all polymers was >220°C. The Affinisol™ polymers exhibited less hygroscopicity than Kollidon ® VA 64 and another HPMC polymer, Methocel™ K100LV. The complex viscosity profiles of the Affinisol™ polymers as a function of temperature were similar. The viscosity of the Affinisol™ polymers was highly sensitive to the shear rate applied, and unlike Kollidon ® VA 64, the viscosity decreased drastically when the angular frequency was increased. Because of the very high shear rate encountered during melt extrusion, Affinisol™ polymers showed capability of being extruded at larger windows of processing temperatures as compared to that of Kollidon ® VA 64.

Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions

“…Given the outcome of this study, an interesting future study would be to further evaluate shear effects in extrusion processing by utilizing more aggressive screw design and increased screw speed. The thermal and rheological behaviors of PVPs have been well studied; thus, it was expected that extrusion of PVP K30 and K90 would be difficult or impossible (50). PVP K30 and K90 have glass transition temperatures around 149°C and 156°C and are known to degrade around 175°C and 200°C, respectively.…”

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review

“…The complex viscosity of neat polymer can be measured by melt rheology and have been correlated to torque limitations in extrusion processing (45). A complex viscosity between 10,000 and 1000 Pa s has been correlated to extrusionprocessing capabilities with 10,000 Pa s being too solid-like and exceeding the torque limitations of a small-scale extruder and 1000 Pa s being too liquid-like to shape through an extruder die (46). A temperature range corresponding to the complex viscosity range between 10,000 and 1000 Pa s establishes the baseline extrusion-processing window when this temperature range is between the glass transition and the degradation temperatures (T g and T deg , respectively) of the polymer.…”

“…The data was predominantly obtained by a series of valuable papers from the group of Dr. Serajuddin (46)(47)(48), along with vendor information and other sources as identified.…”

“…The glass transition and/or melting temperature, the degradation temperature, and the extrusion temperature range based on viscoelastic properties as previously described of polyvinyl-based polymers are shown in Table I (45,46). Polymers such as copovidone, Soluplus®, and Kollicoat IR have a wide extrusion temperature range of more than 20°C, offering greater flexibility in processing.…”

“…Interestingly, the homo block copolymers Eudragit® E PO, Eudragit® RL PO, and Eudragit® RS PO exhibited extrusion-processing windows, but the hetero block copolymers Eudragit® L100, Eudragit® S100, and Eudragit® L100-55 were too viscous to be extruded as neat polymers. Adapted from (46) and (45) MW molecular weight, T g glass transition temperature, T m melt temperature, T deg degradation temperature…”