Phase characterization of indomethacin in binary solid dispersions with PVP VA64 or Myrj 52.

In the present study the properties of binary solid dispersions made up of PVP VA64, Myrj 52 and indomethacin (IMC) are studied and characterized. The solid dispersions were prepared by dissolving the materials in dichloromethane, followed by solvent evaporation under reduced pressure at 55 degrees C in a rotavapor. Binary solid dispersions were characterized by standard and modulated temperature differential scanning calorimetry (MTDSC), thermogravimetry (TGA) and X-ray powder diffraction (XRPD). XRPD analysis showed that the initial IMC was in its gamma-form, and that it was transformed to the beta-form (reported to be a solvate) together with an amorphous fraction in the solid dispersions. A mixture of the beta-form and amorphous IMC was also obtained in the binary systems containing less than 30% polymer. IMC without adding polymer was subjected to the same experimental procedures as in the solid dispersions, and used as a model to characterize the solid-state transformations. The following order of transitions was observed: from the initial gamma-form, the beta-form was obtained together with an amorphous component, then the crystalline beta-form transforms into the alpha-form which melts and recrystallizes into the most stable gamma-form.

Solid state characteristics of ternary solid dispersions composed of PVP VA64, Myrj 52 and itraconazole.

The purpose of the present study was to characterize the solid state properties of ternary solid dispersions made up of PVP VA64, Myrj 52 and itraconazole. The solid dispersions were prepared by dissolving the materials in methylene chloride, followed by evaporation under reduced pressure of the solvent at 55 degrees C in a rotovapor. Binary and ternary solid dispersions were characterized by standard and modulated temperature differential scanning calorimetry and X-ray powder diffraction. Although PVP VA64 and itraconazole were found to be completely miscible in the solid state, addition of a small amount of Myrj 52 to the drug-polymer system leads to separation of itraconazole thus demonstrating that Myrj 52 expels the drug from the polymer phase.

Mucosal response in African catfish after administration of Vibrio anguillarum O2 antigens via different routes.

The aim of this study was to investigate the possibility of mucosal vaccination in African catfish (Clarias gariepinus) with Vibrio anguillarum O2 bacterins. The antigen was administered via different routes: anal intubation, oral administration, intraperitoneal injection and immersion. To monitor the antigen uptake, a competitive ELISA was used. The antibody response was measured using an indirect ELISA. Increased antibody levels were found in bile and mucus upon anal intubation, which was not the case after intraperitoneal injection. The data indicate that oral vaccination of fish may be possible when antigens can reach the second gut segment in sufficient quantities and in the right form as confirmed by the recorded substantial induction of systemic and mucosal immunity. The results obtained are a strong indication for mucosal immune response and the two compartmental models for immune response in fish.

Oral vaccination of African catfish with Vibrio anguillarum O2: effect on antigen uptake and immune response by absorption enhancers in lag time coated pellets.

The impact on antigen uptake and antibody response by the addition of absorption enhancers to Vibrio anguillarum O2 antigen was studied in oral vaccination trials of African catfish (Clarias gariepinus). Oral vaccination was achieved by feeding lag time coated pellets. The lag time coat prevents premature release of the encapsulated vaccine in the tank, before ingestion of the pellets by the fish. To monitor the antigen uptake, a competitive ELISA was used. The antibody response was measured using an indirect ELISA. Feeding of bacterin-layered pellets without absorption enhancers resulted in a rather low antigen uptake and antibody levels. The addition of absorption enhancers such as sodium salicylate, sodium caprate and vitamin E TPGS increased the serum antigen levels and specific antibody levels in the systemic circulation. Skin mucus antibody levels were higher after oral vaccination compared to the IP and control group. The addition of absorption enhancers in the oral groups further increased the antibody levels obtained in the skin mucus.

Study of the phase behavior of polyethylene glycol 6000-itraconazole solid dispersions using DSC.

The aim of the present study was to investigate the phase behavior of solid dispersions made up of PEG 6000 and itraconazole using DSC. Solid dispersions were prepared by solvent evaporation. DSC analysis of pure PEG 6000 showed three endothermic events, representing the melting transitions of the three different crystal modifications. It was shown that itraconazole decreased the formation of the polymer modifications with melting transitions at 56 and 59 degrees C but promoted the formation of the modification with a melting transition at 63 degrees C. All dispersions investigated showed the presence of crystalline itraconazole indicating that the drug is not molecularly dispersed in the polymer matrix. However, the presence of an endothermic peak in DSC curves of all solid dispersions at approximately 85-90 degrees C showed that at least a second phase of pure itraconazole is present also: glassy itraconazole. The protective effect of the polymer is clear at low concentration of drug since no recrystallisation exotherm can be detected. However, at drug concentrations at or above 80%, a recrystallization exotherm at approximately 117 degrees C can be detected. At least three different phases can be distinguished at room temperature: a polymer phase, crystalline itraconazole and glassy itraconazole. The findings of the present study thus demonstrate the coexistence of multiple drug phases in a solid dispersion.

Development of a lag time coating for drug-layered fish feed pellets.

The purpose of this work was to develop a release-delaying coat for drug-layered fish pellets, in order to prevent a premature release of the drug in the tank water but allowing a rapid release after uptake by the fish. Blank pellets were prepared in a rotary processor and drug layered in a Wurster coater with bovine serum albumin or riboflavin using hydroxypropyl methyl cellulose (HPMC) as a binder. On the drug-loaded pellets, different mixtures of ethyl cellulose (EC) and HPMC were applied as the release-delaying coat. The aim was to obtain less than 10% drug release during the first 10 min followed by a fast release after the "lag" period, resulting in a sigmoidal release profile. In order to prevent coat bursts it was necessary to increase the amount of plasticizer from 20 to 40% triethylcitrate. To have a complete coat around the pellets, the thickness of the coat (amount EC) was important up to a certain level. The EC/HPMC ratio had a decisive influence on optimizing the permeability of the coating and realizing a sigmoidal release profile. The release rate was studied as a function of several formulation variables and physicochemical parameters (salinity, pH, and temperature) of the dissolution medium as the coating system is intended for different fish species. Salinity of the water proved to be important as well as the temperature. The developed system seems to be promising for a lot of ichthyologic applications, although it has to be evaluated for each intended drug, keeping in mind the properties of the particles to be coated, the fish species, and the environment.

Comparative evaluation of co-processed lactose and microcrystalline cellulose with their physical mixtures in the formulation of folic acid tablets.

In this study, a new co-processed filler-binder ingredient for direct compression, MicroceLac 100, was compared with three different lactoses mixed with microcrystalline cellulose. The aim was to improve a folic acid tablet formulation. Therefore, the influence of drug addition to these mixtures was studied with regard to flow and binding properties. Another part of the study was focused on the interaction and segregation behavior of the drug. MicroceLac 100 showed superior flow and binding properties. Good adhesion of folic acid to the MicroceLac 100 particles could decrease demixing and segregation. The improved characteristics of co-processed material are attributed to spray drying. Sodium stearyl fumarate was chosen as a lubricant, based on ejection force measurements. The content uniformity of the newly formulated direct compression tablets met the official requirements.