Impact of drying on solid state modifications and drug distribution in ibuprofen-loaded calcium stearate pellets.

Drying is a common pharmaceutical process, whose potential to alter the final drug properties-even at relatively low temperatures-is often neglected. The present study addresses the impact of drying at 20 and 50 °C on wet-extruded calcium stearate (CaSt) pellets. Drying at 20 °C caused the majority of ibuprofen to accumulate at the pellet surface due to a strong convective flow from the pellet's center to the surface. In contrast, pellets dried at 50 °C still contained ibuprofen in the pellet's interior due to the higher drying rate and the associated film breakage during drying. Moreover, the higher drying temperature caused CaSt to form a second lamellar phase and ibuprofen to convert (partly) into its amorphous state. Overall, the drying process affected the solid state and the spatial ibuprofen distribution within the pellet. Knowledge of these effects can aid in tailoring advanced multipellet formulations.

Generation of endocrine disruptor compounds during ozone treatment of tannery wastewater confirmed by biological effect analysis and substance specific analysis.

Ozone (O3) with its high oxidation potential was used to degrade or eliminate pollutants contained in tannery wastewater when applying different pHs and quantities of O3. Our objective was a chemical degradation by O3 to achieve an enhancement of biodegradability, with a parallel decrease in toxicity. Conventional analyses and bioassays beside substance specific analyses were performed to clear-up the behaviour of wastewater content from tanning process. The results demonstrate that the dominant organic pollutants were chemically degraded by oxidation as the chemical and biochemical oxygen demand (COD and BOD) prove, while changes in carbon content monitored by total or dissolved organic carbon content (TOC or DOC) were only marginal. Vibrio fischeri and Daphnia magna toxicity testing performed in parallel proved a decrease in toxicity after O3-treatment, while the estrogenic activity determined by enzyme-linked receptor assay (ELRA), however, proved an increase of endocrine disruptor compounds (EDC). Results could be explained by substance-specific analyses using gas chromatography (GC-MS) and liquid chromatography/mass spectrometry (LC-MS). From GC-MS analysis the elimination of non-polar compounds could be recognized, whereas the oxidative conversion led to an increase of EDC compounds, which qualitatively could be identified by LC-MS as nonylphenol ethoxylate (NPEO) degradation products: short chain NPEOs, nonylphenol carboxylates (NPECs) and nonylphenol (NP).

Injection molding as a one-step process for the direct production of pharmaceutical dosage forms from primary powders.

The objective of the present study was to develop a one-step process for the production of tablets directly from primary powder by means of injection molding (IM), to create solid-dispersion based tablets. Fenofibrate was used as the model API, a polyvinyl caprolactame-polyvinyl acetate-polyethylene glycol graft co-polymer served as a matrix system. Formulations were injection-molded into tablets using state-of-the-art IM equipment. The resulting tablets were physico-chemically characterized and the drug release kinetics and mechanism were determined. Comparison tablets were produced, either directly from powder or from pre-processed pellets prepared via hot melt extrusion (HME). The content of the model drug in the formulations was 10% (w/w), 20% (w/w) and 30% (w/w), respectively. After 120min, both powder-based and pellet-based injection-molded tablets exhibited a drug release of 60% independent of the processing route. Content uniformity analysis demonstrated that the model drug was homogeneously distributed. Moreover, analysis of single dose uniformity also revealed geometric drug homogeneity between tablets of one shot.

Applicability of Fenton and H2O2/UV reactions in the treatment of tannery wastewaters.

In this paper we evaluated the H2O2/UV and the Fenton's oxidation processes for the treatment of tannery wastewater under different experimental conditions. Efficiencies were judged by the amounts of organic substances degraded or eliminated under these treatment techniques. Daphnia magna and Vibrio fischeri were used to monitor toxicity. Organic compounds contained in the untreated and treated tannery wastewater were determined and identified using substance specific techniques. Gas chromatography-mass spectrometry (GC-MS) in positive electron impact (EI(+)) mode was applied to determine volatile organics. Atmospheric pressure ionization (API) mass (MS) and tandem mass spectrometry (MS-MS) coupled with flow injection analysis (FIA) or liquid chromatography (LC) were used to detect or identify polar organic pollutants. The experimental results indicated that both oxidation processes--H2O2/UV at pH 3 and Fenton at pH 3.5--are able to reduce TOC content by mineralisation of the organic compounds.

Alcohol dose dumping: The influence of ethanol on hot-melt extruded pellets comprising solid lipids.

The objective of the present study was to investigate interactions between alcohol and hot-melt extruded pellets and the resulting drug release behavior. The pellets were composed of vegetable calcium stearate as matrix carrier and paracetamol or codeine phosphate as model drugs. Two solid lipids (Compritol® and Precirol®) were incorporated into the matrix to form robust/compact pellets. The drug release characteristics were a strong function of the API solubility, the addition of solid lipids, the dissolution media composition (i.e., alcohol concentration) and correspondingly, the pellet wettability. Pellets comprising paracetamol, which is highly soluble in ethanol, showed alcohol dose dumping regardless of the matrix composition. The wettability increased with increasing ethanol concentrations due to higher paracetamol solubilities yielding increased dissolution rates. For pellets containing codeine phosphate, which has a lower solubility in ethanol than in acidic media, the wettability was a function of the matrix composition. Dose dumping occurred for formulations comprising solid lipids as they showed increased wettabilities with increasing ethanol concentrations. In contrast, pellets comprising calcium stearate as single matrix component showed robustness in alcoholic media due to wettabilities that were not affected by the addition of ethanol. The results clearly indicate that the physico-chemical properties of the drug and the matrix systems are crucial for the design of ethanol-resistant dosage forms. Moreover, hydrophobic calcium stearate can be considered a suitable matrix system that minimizes the risk of ethanol-induced dose dumping for certain API's.

The effect of the drying temperature on the properties of wet-extruded calcium stearate pellets: pellet microstructure, drug distribution, solid state and drug dissolution.

Although drying is widely applied during the manufacturing of solid dosage forms, its potential effect on the product's (key) properties is often underestimated. Hence, the present study addresses drying related modifications of wet-extruded pellets comprising calcium stearate (CaSt, matrix former) and ibuprofen (model drug). After spheronization, the pellets were tray dried at different temperatures. The dried pellets were evaluated regarding their microstructure, the ibuprofen distribution, solid state modifications and the resulting in-vitro dissolution profiles. The ibuprofen distribution profiles along the pellets' cross-sections varied for the different drying conditions. The profiles turned from inhomogeneous to uniform with increasing drying temperature. Temperatures above 20°C yielded solid state modifications, including ibuprofen transition into the amorphous state and the formation of eutectic compositions. As none of the batches exhibited a high specific surface area associated with an open, well-interconnected pore system, the dissolution profiles were a function of the ibuprofen distribution. Differences in the solid state did not contribute to the dissolution behavior, since the CaSt matrix did not swell or dissolve in the dissolution medium. These findings show that drying may considerably affect the final product properties even for moderate drying conditions.

Linking a medical vocabulary to a clinical data model using Abstract Syntax Notation 1.

We have created a clinical data model using Abstract Syntax Notation 1 (ASN. 1). The clinical model is constructed from a small number of simple data types that are built into data structures of progressively greater complexity. Important intermediate types include Attributes, Observations, and Events. The highest level elements in the model are messages that are used for inter-process communication within a clinical information system. Vocabulary is incorporated into the model using BaseCoded, a primitive data type that allows vocabulary concepts and semantic relationships to be referenced using standard ASN. 1 notation. ASN. 1 subtyping language was useful in preventing unbounded proliferation of object classes in the model, and in general, ASN.1 was found to be a flexible and robust notation for representing a model of clinical information.

Elucidation of the behavior of tannery wastewater under advanced oxidation conditions.

Diverse advanced oxidation process (AOP) techniques applying UV, TiO2/UV, O3 and O3/UV were used to degrade pollutants contained in tannery wastewater. The total mineralization of these pollutants is desirable, but it is quite energy consuming and sometimes impossible. Therefore the objective was to achieve an enhancement of biodegradability, preferentially with a decrease in toxicity in parallel. This work demonstrates that the dominant pollutants were chemically degraded by oxidation, while changes in carbon content were only marginal. These results were obtained monitoring the total organic carbon content (TOC), chemical and biochemical oxygen demand (COD and BOD), and substance-specific pollutant content by application of gas chromatography/mass spectrometry (GC-MS) and liquid chromatography/mass spectrometry (LC-MS). Daphnia magna toxicity testing performed in parallel proved a decrease in toxicity after AOP treatment of the tannery wastewater.

Comparison of different advanced oxidation process to reduce toxicity and mineralisation of tannery wastewater.

Many organic compounds contained in wastewater are resistant to conventional chemical and/or biological treatment. Because of this reason different degradation techniques are studied as an alternative to biological and classical physico-chemical processes. Advanced Oxidation Processes (AOPs) probably have developed to become the best options in the near future. AOP while making use of different reaction systems, are all characterised by the same chemical feature: production of OH radicals (*OH). The versatility of AOPs is also enhanced by the fact that they offer different possibilities for OH radical production, thus allowing them to conform to specific treatment requirements. The main problem with AOPs is their high cost. The application of solar technologies to these processes could help to diminish that problem by reducing the energy consumption required for generating UV radiation. In this work, different AOPs (O3, TiO2/UV, Fenton and H2O2/UV) were examined to treat tannery wastewater or as a pre-treatment step for improving the biodegradation of tannery wastewater, at different pH and dosage of the chemicals. Under certain circumstances retardation in biodegradation and/or an increase in toxicity may be observed within these treatment steps. Two different bioassays (Daphnia magna and Vibrio fischeri) have been used for testing the progress of toxicity during the treatment. In parallel other objectives were to analyse and identify organic compounds present in the untreated wastewater and arising degradation products in AOP treated wastewater samples. For this purpose substance specific techniques, e.g., gas chromatography-mass spectrometry (GC-MS) in positive electron impact (El(+)) mode and atmospheric pressure ionisation (API) in combination with flow injection analysis (FIA) or liquid chromatography-mass and tandem mass spectrometry (LC-MS or LC-MS-MS) were performed.