Melt-Extruded Eudragit® FS-Based Granules for Colonic Drug Delivery

Abstract

Abstract. The purpose of this study is to characterize the properties of Eudragit® FS-based granules prepared using melt extrusion process for colonic drug delivery. 5-Aminosalicylic acid (5-ASA), theophylline, and diclofenac sodium were used as the model compounds. Drug and polymer blends were meltextruded into thin rods using a single screw extruder. Drugs were found to be dispersed as crystalline particles in the granules. A hammer mill was used to reduce the extrudate into 16-40 mesh granules, which were mixed with lactose and filled into hard gelatin capsules. Three-stage dissolution testing performed using USP paddle method was used to simulate drug release in gastrointestinal tract. In this study, melt extrusion has been demonstrated to be a suitable process to prepare granules for colonic delivery of 5-amino salicylic acid. At 30% drug loading, less than 25% 5-ASA was released from melt-extruded granules of 20-30 mesh in the first two stages (0.1 N hydrochloric acid solution and phosphate buffer pH 6.8) of the dissolution testing. All 5-ASA was released within 4 h when dissolution medium was switched to phosphate buffer pH 7.4. Drug loading, granule size, and microenvironment pH induced by the solubilized drug were identified as the key factors controlling drug release. Granules prepared with melt extrusion demonstrated lower porosity, smaller pore size, and higher physical strength than those prepared with conventional compression process. Eudragit® FS was found to be stable even when processed at 200°C.

Chronotherapeutic Drug Delivery of Ketoprofen and Ibuprofen for Improved Treatment of Early Morning Stiffness in Arthritis Using Hot-Melt Extrusion Technology

“…This is attributed to the increased surface area due to the smaller particle size of the powdered formulation. Sustained drug release from the larger pellet size could be attributed to either the lower surface area of the larger pellets compared to the smaller pellets or increased average distance for diffusion of the active ingredient from the pellet (33).…”

Development and Characterization of Sustained-Released Donepezil Hydrochloride Solid Dispersions Using Hot Melt Extrusion Technology

“…The MCC is not completely impeded within tablet matrix. However, interconnection bond after melting the lipid [27][28][29] and intragranular and intergranular bonds within the lipid while extruding the blends might occur [30]. Therefore, it can be concluded that this fusion bonding of MCC with the lipid while extruding made the MCC completely embedded within the matrix and prevented tablet splitting and burst release in the dissolution media, instead leading to the complete disintegration that occurred after 2 h in our case when MCC was not co-processed via HME with the rest of formulation components.…”

“…During the initial stage of the dissolution test, the drug clusters located on the surface of the granules were readily released into the dissolution medium. As the dissolution process progressed, fewer drug clusters were accessible to the dissolution medium, and a plateau was reached [29]. This plateau behavior was because the mixture was under the percolation threshold.…”

“…This plateau behavior was because the mixture was under the percolation threshold. Below this threshold, incomplete drug release is observed, presumably due to the limited accessibility of many drug particles to the dissolution medium since they are encapsulated by water-insoluble polymeric materials [29,40].…”

Recent advances in mesalamine colonic delivery systems

“…It was concluded that the optimized formulation, was able to retard the drug release at the low pH and control it at intestinal pH, which makes it a promising colon-specific delivery system. Zhang et al [25] investigated the development a colon delivery system, using melt-extruded granules of mesalamine and Eudragit® FS. The developed product exhibited higher physical strength, smaller pore size and lower porosity compared with the conventionally prepared granules.…”