Physicochemical properties of film-coated melt-extruded pellets.

The purpose of this study was to investigate the physicochemical properties of poly(ethylene oxide) (PEO) and guaifenesin containing beads prepared by a melt-extrusion process and film-coated with a methacrylic acid copolymer. Solubility parameter calculations, thermal gravimetric analysis (TGA), scanning electron microscopy (SEM), modulated differential scanning calorimetry (MDSC), X-ray powder diffraction (XRPD) and high performance liquid chromatography (HPLC) were used to determine drug/polymer miscibility and/or the thermal processibility of the systems. Powder blends of guaifenesin, PEO and functional excipients were processed using a melt-extrusion and spheronization technique and then film-coated in a fluidized bed apparatus. Solubility parameter calculations were used to predict miscibility between PEO and guaifenesin, and miscibility was confirmed by SEM and observation of a single melting point for extruded drug/polymer blends during MDSC investigations. The drug was stable following melt-extrusion as determined by TGA and HPLC; however, drug release rate from pellets decreased upon storage in sealed HDPE containers with silica desiccants at 40 degrees C/75% RH. The weight loss on drying, porosity and tortuosity determinations were not influenced by storage. Recrystallization of guaifenesin and PEO was confirmed by SEM and XRPD. Additionally, the pellets exhibited a change in adhesion behaviour during dissolution testing. The addition of ethylcellulose to the extruded powder blend decreased and stabilized the drug release rate from the thermally processed pellets. The current study also demonstrated film-coating to be an efficient process for providing melt-extruded beads with pH-dependent drug release properties that were stable upon storage at accelerated conditions.

Physicochemical characterization and mechanisms of release of theophylline from melt-extruded dosage forms based on a methacrylic acid copolymer.

The purpose of the current study was to investigate the physicochemical properties of melt-extruded dosage forms based on Acryl-EZE and to determine the influence of gelling agents on the mechanisms and kinetics of drug release from thermally processed matrices. Acryl-EZE is a pre-mixed excipient blend based on a methacrylic acid copolymer that is optimized for film-coating applications. Powder blends containing theophylline, Acryl-EZE, triethyl citrate and an optional gelling agent, Methocel K4M Premium (hydroxypropyl methylcellulose, HPMC, hypromellose 2208) or Carbopol 974P (carbomer), were thermally processed using a Randcastle single-screw extruder. The physical and chemical stability of materials during processing was determined using thermal gravimetric analysis and HPLC. The mechanism of drug release was determined using the Korsmeyer-Peppas model and the hydration and erosion of tablets during the dissolution studies were investigated. The excipient blends were physically and chemically stable during processing, and the resulting dosage forms exhibited pH-dependent dissolution properties. Extrusion of blends containing HPMC or carbomer changed the mechanism and kinetics of drug release from the thermally processed dosage forms. At concentrations of 5% or below, carbomer was more effective than HPMC at extending the duration of theophylline release from matrix tablets. Furthermore, carbomer containing tablets were stable upon storage for 3 months at 40 degrees C/75% RH. Thus, hot-melt extrusion was an effective process for the preparation of controlled release matrix systems based on Acryl-EZE.

Compression of controlled-release pellets produced by a hot-melt extrusion and spheronization process.

The purpose of this study was to investigate the physicomechanical and dissolution properties of tablets containing controlled-release pellets prepared by a hot-melt extrusion and spheronization process. A powder blend of anhydrous theophylline, Eudragit Preparation 4135 F, and functional excipients was melt-extruded, pelletized, and then spheronized. The pellets were compressed into tablets using forces of 5, 10, 15, and 20 kN. Tablet diluents included microcrystalline cellulose, a mixture of spray-dried lactose and microcrystalline cellulose, modified food starch, and soy polysaccharides. The effective porosity of the compressed pellets was measured using mercury porosimetry and helium pycnometry, while the surface area was determined using Brunauer, Emmett, and Teller (BET) analysis. The disintegration time, hardness, and friability of compacts were determined. Drug release studies were performed according to USP 27 Apparatus 3 guidelines in 250 mL of medium (pH 1.0, 3.0, 5.0, 6.8, and 7.4) 37 degrees C and 20 dpm. Samples were analyzed by high pressure-liquid chromatography (HPLC). Effective porosity and surface area determinations of the melt-extruded pellets were not influenced by compression. The percent of theophylline released from rapidly disintegrating tablets was not affected by compression force or excipient selection, but tablets with prolonged disintegration times exhibited delayed drug release in acidic media. However, dissolution profiles of uncompressed pellets and all compacts were identical after transition from 0.1 N HCl to media increasing in pH from 3.0 to 7.4. Furthermore, pellet to filler excipient ratio and filler excipient selection did not influence the rate of drug release from compacts.