Novel Hot Melt Extruded Matrices of Hydroxypropyl Cellulose and Amorphous Felodipine–Plasticized Hydroxypropyl Methylcellulose as Controlled Release Systems

Abstract

Hydroxypropyl methylcellulose (HPMC) is a hydrophilic retarding-release polymer with the limited application in hot melt extrusion (HME) due to its high glass transition temperature (T g 181-191°C) and melt viscosity. The aim of this study is to develop hot melt extruded matrices using hydroxypropyl cellulose (HPC) and felodipine (FLDP) with HPMC for controlled release and explore the relations of their specialty, processability, and structure with the product properties. Results showed that FLDP/HPC EF /HPMC can be extruded at 160°C with torques not more than 0.5 N•m. The extruded matrices of FLDP/HPC EF /HPMC K15M (10:45:45 and 30:35:35) achieved the controlled release for 24 h. Rheological behaviors demonstrated that HPC EF and FLDP were miscible with HPMC K15M , attaining maximum 30% FLDP soluble in the molten mixtures. HPC EF and FLDP decreased the complex viscosity and plasticized HPMC K15M to improve the extrusion processing. DSC and FT-IR indicated that the molten soluble FLDP was amorphous in the extruded matrices by hydrogen bonding with HPC EF /HPMC K15M . SEM/energy-dispersive X-ray microanalysis illustrated that the microstructure of extrudates was surface dense and interior loose, and FLDP was homogenously dispersed. Three-point bending test revealed that the plasticizers of HPC EF and FLDP contributed differently to the mechanical properties. HPC EF decreased the flexural modulus of HPMC K15M while that of HPC EF /HPMC K15M was increased by FLDP. Besides controlled release, low moisture absorption and enhanced stability were also the correlated achievements. Therefore, HPC EF -combined poorly water-soluble drugs to plasticize HPMC K15M provide an alternative novel potential approach to realize the controlled-release delivery via HME.

Thermo-Structural Characterization of Phase Transitions in Amorphous Griseofulvin: From Sub-Tg Relaxation and Crystal Growth to High-Temperature Decomposition

“…In modern pharmaceutical research and industry, the high-temperature stability of amorphous drugs becomes increasingly more relevant due to individual patient targeting via controlled-release tablets and capsules, where the key processing technology is either hot-melt extrusion (HME) or 3D-printing (3DP) [22][23][24][25]. Since GSF is a high-dosage drug [9], processing temperatures in the vicinity or even exceeding its T g need to be used as a bare minimum in the corresponding formulations in order to achieve the required cohesion of the HME/3DP-produced filaments [26][27][28][29][30][31][32][33]. This makes the temperature-induced crystallization of GSF a very relevant issue, even at temperatures close to T g .…”

Comparison of Hydroxypropylcellulose and Hot-Melt Extrudable Hypromellose in Twin-Screw Melt Granulation of Metformin Hydrochloride: Effect of Rheological Properties of Polymer on Melt Granulation and Granule Properties

“…Especially when it comes to melt extrusion, polymeric materials such as high-molecular-weight grades of hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) may sometimes be used in melt extrusion but have processing difficulties due to their thermomechanical properties. These grades of HPMC and PVP may require the addition of plasticizer to lower the processing temperature for extrusion [19,20]. In contrast, high-molecular-weight HPC does not show any processing difficulties and can be extruded without the addition of plasticizer [21].…”