Stability Of Theophylline Research Articles

The influence of ethylcellulose polymers on the physical stability of theophylline pellets coated with Eudragit NE 30 D

The objective of this study was to investigate the influence of ethylcellulose (EC), a high glass transition temperature, non-enteric polymer, on the physical stability and drug release properties of theophylline from pellets coated with the poorly permeable, pH-independent, sustained release coating dispersion, Eudragit NE 30 D. The effect of EC addition on drug release from coated pellets, as well as the physico-mechanical, water vapor permeability, and thermal properties of sprayed films was investigated. The particle size of EC, when mixed in a ratio of 1:1 with the acrylic polymer, affected the drug release rate, with those formulations possessing a smaller particle size exhibiting increased drug release rates. When EC having a mean particle size of 9 μm was present in the acrylic films at a ratio of 1:2, 60% drug was released over 18 h. The drug release rate from these coated theophylline pellets was stable over 3 months at both 25°C/60% RH and 40°C/75% RH when stored in aluminum induction sealed, high density polyethylene (HDPE) containers. Sprayed films stored under the same conditions showed no change in the water vapor permeability and physico-mechanical properties. Modulated differential scanning calorimetry showed three transitions in the composite films, corresponding to the glass transition temperature of Eudragit NE 30 D, ethylcellulose, and a third miscible phase. This third miscible phase was determined to consist of 85% ethylcellulose and 15% acrylic polymer and occupied only a small fraction of the total film.

A simple and rapid HPLC/UV method for the simultaneous quantification of theophylline and etofylline in human plasma

A simple, sensitive and selective high performance liquid chromatography (HPLC) method with ultraviolet detection (272 nm) was developed and validated for the simultaneous quantification of theophylline and etofylline in human plasma. Following rapid sample preparation, the analytes and internal standard (hydrochlorothiazide) were separated using an isocratic mobile phase on a reverse phase C 18 column. The lower limit of quantification was 100 ng/mL for both theophylline and etofylline with a relative standard deviation of less than 6%. A linear dynamic range of 100–10,000 ng/mL for both theophylline and etofylline was established. This HPLC method was validated with between-batch precision of 2.2–6.0 and 1.4–3.7% for theophylline and etofylline, respectively. The between-batch accuracy was 94.3–98.0 and 95.4–98.2%, respectively. Stability of theophylline and etofylline in plasma was excellent, with no evidence of degradation during sample processing (autosampler) and 30 days storage in a freezer. This validated method is simple and rugged enough to be used in pharmacokinetic studies.

Dehydration Studies Using a Novel Multichamber Microscale Fluid Bed Dryer with In‐Line Near‐Infrared Measurement

The purpose of this research was to study the effect of two process parameters (temperature and moisture content) on dehydration behavior of different materials using a novel multichamber microscale fluid bed dryer with a process air control unit and in‐line near‐infrared (NIR) spectroscopy. The materials studied were disodium hydrogen phosphates with three different levels of hydrate water and wet theophylline granules. Measured process parameters of fluid bed drying were logged, including in‐line NIR signals. Off‐line analyses consisted of X‐ray powder diffraction patterns, Fourier transform NIR spectra and moisture contents of studied materials. During fluid bed drying, the stepwise dehydration of materials was observed by the water content difference of inlet and outlet air, the pressure difference over the bed, and the in‐line NIR spectroscopy. The off‐line analysis confirmed the state of solid materials. The temperature and the moisture content of the process air were demonstrated to be significant factors for the solid‐state stability of theophylline. The presented setup is a material and cost‐saving approach for studying the influence of different process parameters on dehydration behavior during pharmaceutical processing. © 2003 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 92:2074–2081, 2003

Stability of Fluconazole in Injectable Solutions

The stability of fluconazole 1 mg/mL in several injectable solutions at 25 degrees C over 72 hours was studied. Fluconazole 2 mg/mL was mixed in a 1:1 ratio with 5% dextrose injection, lactated Ringer's injection, potassium chloride 20 meq/L in 5% dextrose injection, heparin sodium 100 units/mL in 5% dextrose injection, theophylline 0.8 mg/mL in 5% dextrose injection, and morphine sulfate 0.5 mg/mL in 5% dextrose injection. Three 1-mL samples were taken from each admixture at 0, 6, 12, 24, 36, 48, and 72 hours and analyzed for fluconazole concentration by stability-indicating gas chromatography. Fluconazole 2 mg/mL was stable in potassium chloride plus 5% dextrose injection and in theophylline plus 5% dextrose injection for 72 hours. Fluconazole was stable in the other injectable solutions for 24 hours. The stability of theophylline, heparin, or morphine sulfate in the presence of fluconazole was not studied. Fluconazole was stable in potassium chloride 20 meq/L plus 5% dextrose injection and in theophylline 0.8 mg/mL plus 5% dextrose injection for 72 hours and stable in the other injectable solutions for 24 hours.

Stability of theophylline in human serum and whole blood

The effect of various storage conditions on serum theophylline results using a fluorescence polarization immunoassay (FPI) method was studied. Two human subjects received sufficient oral theophylline to produce low and high therapeutic serum theophylline concentrations. Aliquots of venous whole blood (without anti-coagulant) and serum from each subject were sealed in polypropylene plastic and glass containers and stored at 4 degrees C and 25 degrees C. Additional aliquots of serum from each subject were stored in glass and polypropylene containers at -20 degrees C. FPI assays were performed on days 0 and 3 for room temperature serum samples, days 3 and 7 for refrigerated serum samples, and days 3, 7, 14, 28, 56, 168, and 336 for frozen serum samples. All whole blood samples were assayed on day 3 after removal of the clot. Some samples were tested using FPI for 1,3-dimethyluric acid, a metabolite of theophylline, and results from spiked samples and samples tested with high-pressure liquid chromatography were compared with FPI results to determine cross-reactivity of the metabolite. No appreciable change in the assayed theophylline values occurred under any storage temperature, nor was there any difference in results from samples stored in glass versus polypropylene containers. At a concentration of 20 micrograms/ml, 1,3-dimethyluric acid produced a cross-reactivity of 3.5% with the FPI system. The FPI method is not affected by storage of samples under the specified conditions over the time period studied.