John J. Koleng

Stability of polyethylene oxide in matrix tablets prepared by hot-melt extrusion

The thermal stability of polyethylene oxide (PEO) in sustained release tablets prepared by hot-melt extrusion was investigated. The weight average molecular weight of the polymer was studied using gel permeation chromatography. The chemical stability of PEO was found to be dependent on both the storage and processing temperature, and the molecular weight of the polymer. Storage of the polymer above its melting point significantly increased polymer degradation, and the degradation process was accelerated as the molecular weight was reduced. The thermal stability of PEO MW = 1,000,000 (PEO 1 M) in sustained release chlropheniramine maleate (CPM) tablets prepared by hot-melt extrusion was found to depend on the processing temperature and screw speed. Lower molecular weight PEO MW = 100,000 (PEO 100 K) was demonstrated to be a suitable processing aid for PEO 1 M. Incorporation of PEO 100 K reduced degradation of PEO 1 M and did not alter the release rate of CPM. Vitamin E, Vitamin E Succinate and Vitamin E TPGS were found to be suitable stabilizers for PEO, however, ascorbic acid was shown to degrade the polymer in solution. Thermal analysis demonstrated that Vitamin E Succinate and Vitamin E TPGS were dispersed at the molecular level in hot-melt extruded tablets. Solubilized Vitamin E Succinate and Vitamin E TPGS suppressed the melting point of the polyethylene oxide. Drug release rates from hot-melt extruded tablets stabilized with antioxidants were found to be dependent on the hydrophilic nature of the antioxidant.

Production of spherical pellets by a hot-melt extrusion and spheronization process.

Controlled-release theophylline containing spherical pellets were successfully produced by a hot-melt extrusion (HME) and spheronization process. A powder blend of anhydrous theophylline, Eudragit Preparation 4135 F, microcrystalline cellulose and polyethylene glycol 8000 powder was sieved, blended and then melt-extruded in a Randcastle Microtruder. The hot-melt extruded pellets were prepared by first cutting a thin, extruded composite rod into symmetrical pellets. The pellets were then spheronized in a traditional spheronizer at an elevated temperature. Thermal properties of the pellet formulation components and the hot-melt extrudate were studied to determine suitability of the formulation for HME. Pellets were examined using scanning electron microscopy to determine the effect of spheronization time on surface morphology. The rate of release of theophylline from the hot-melt extruded spherical pellets was characterized using USP 24 Apparatus 2 dissolution testing after initial pellet production and after 1 year storage in sealed HDPE containers at 25 degrees C/60% RH.

The Influence of Polymeric Subcoats and Pellet Formulation on the Release of Chlorpheniramine Maleate from Enteric Coated Pellets

Abstract The influences of aqueous polymeric subcoats and pellet composition on the release properties of a highly water-soluble drug, chlorpheniramine maleate (CPM), from enteric coated pellets were investigated. Three different aqueous polymeric subcoats, Eudragit® RD 100, Eudragit® RS 30D, and Opadry® AMB, were applied to 10% w/w CPM-loaded pellets that were then enteric coated with Eudragit® L 30D-55. Observed drug release from the coated pellets in acidic media correlated with water vapor transmission rates derived for the subcoat films. The influence of pellet composition on retarding the release of CPM from enteric coated pellets in 0.1 N HCl was investigated. The rate of drug release was greatest for pellets prepared with lactose, microcrystalline cellulose, or dibasic calcium phosphate compared with pellets formulated with citric acid and microcrystalline cellulose. Citric acid reduced the pellet micro-environmental pH, decreasing the amount of drug leakage in 0.1 N HCL during the first 2 hr of dissolution. Polymer flocculation was observed when CPM was added to the Eudragit L 30D-55 dispersion. An adsorption isotherm was generated for mixtures of CPM and the polymer and the data were found to fit the Freundlich model for adsorption. Adsorption of CPM to the polymer decreased with the addition of citric acid to the drug-polymer mixtures.

Influence of metering chamber volume and water level on the emitted dose of a suspension-based pMDI containing propellant 134a

AbstractPurpose. To determine the influence of metering chamber volume of a valve and water content of an aerosol formulation containing propellant 134a on dose delivery through the valve (DDV) and aerodynamic particle size distribution of the emitted dose. Methods. The drug was admixed with ethanol, sonicated, and metered into cans. Valois DF10 RC valves were crimped onto the cans and propellant 134a was gassed through the valve. The DDV was determined using a dosage sampling tube. Aerodynamic particle size distributions were determined by cascade impaction. The water content was determined by Karl Fisher titration. Results. The DDV increased linearly and the aerodynamic particle size distribution was not influenced as the metering chamber volume of the valve was increased. More drug was emitted from the valve from the initial actuations of the can than from the end. Valves with larger metering chamber volumes demonstrated less variability in DDV than those with smaller metering chamber volumes for the initial actuations. The DDV determined for actuations at the end of the can decreased as water was added extemporaneously. The mass median aerodynamic diameter (MMAD) increased as the water level was increased in the formulation. The geometric standard deviation (GSD) and percent respirable fraction (RF) were not influenced by metering chamber volume or water content. Conclusions. The valve chosen for the development of pressurized metered dose inhaler (pMDI) formulations with propellant HFA 134a must be investigated to determine the uniformity of drug delivery. The presence of water influences the characteristics of the emitted dose.