The present study focused on the effect of different feed frame components on the residence time distribution of a three-chamber feed frame system (Fill-O-Matic). A production-scale rotary tablet press was used to simulate the industrial manufacture of tablets. The powder residence time distribution was used to characterize the powder behavior in the Fill-O-Matic. Therefore, two powder blends based on microcrystalline cellulose, one of them serving as a plain powder blend (MCC blend) and the other blend (tracer blend) spray colored with an indigo carmine solution by a fluid bed granulator, were used. With these powder blends, the effect of the reduction of the Fill-O-Matic volume with a perspex disc on the residence time distribution was compared with the standard configuration of the Fill-O-Matic. Furthermore, the filling wheel design with regard to the rod shape and different gap size configurations between the feed frame and the die disc were investigated. Interestingly, the reduction of the feed frame volume led to a remarkable decrease of the mean residence time and the mean centered variance. Moreover, the results of the filling wheel design showed that the rod shape of the filling wheels had a high influence on the intermixing of the powder particles in the filling chamber, whereas the corresponding tablet weights and their relative standard deviation were not affected. The gap size between the feed frame and the die disc had low influence on the residence time distribution but an effect on the tablet weights and their standard deviation.

The objective of the systematic review is to provide complete and updated information on efficacy and safety of sublingual immunotherapy (SLIT) formulations for the treatment of allergic respiratory diseases (ARDs). The literature search was conducted on PubMed database, involving double-blind, randomized clinical trials published between January 1992 and 2018, written in English, and performed in humans. The number of articles finally selected for review was 112. Data from the majority of properly controlled clinical trials demonstrate that SLIT is effective not only with short-term use (first year) but also with long-term use (up to the third year of active therapy), for treating ARDs in children and adults. Both continuous and discontinuous schemes of administration showed significant reductions in symptom and medication scores. Moreover, a SLIT-induced disease-modifying effect has been documented mainly with grass pollen extracts, since improvement is maintained during at least 2 years of follow-up after a 3-year treatment period. Additionally, allergen immunotherapy should also be considered a preventive strategy, especially for decreasing bronchial asthma incidence in children and adolescents with allergic rhinitis treated with SLIT. This therapy is also safe, producing only a few mainly local and mild-to-moderate adverse events, and usually self-limited in time. The registration and authorization of allergen SLIT preparations (grasses and house-dust mite tablets) as drugs by regulatory agencies, such as the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA), has represented a landmark in allergy immunotherapy research. Further long-term studies, specially designed with allergens other than grass pollen or house-dust mites, not only in allergic rhinoconjunctivitis but also on asthmatic subjects, as well as studies comparing different administration schedules and/or routes, are required in order to continue the progress in the modern development of this particularly promising therapy.

Solid dispersions production is one of the substantial approaches for improvement of poor drug solubility. Additionally, supercritical fluid assisted method for preparation of solid dispersions can offer many advantages in comparison to the conventional melting or solvent-evaporation methods. Miscibility analysis provides valuable guidance for selection of the most appropriate polymeric carrier for dispersion of the drug of interest. In addition to the increased drug release rate, solid dispersions should have proper mechanical attributes in order to be successfully formulated in the final solid dosage form such as tablet. Therefore, several pharmaceutical grade polymers have been selected for development of BCS Class II drug carvedilol (CARV) solid dispersions. They were compared based on behavior in supercritical CO2 and affinity towards CARV calculated from the miscibility analysis. By utilization of the supercritical CO2 assisted method, solid dispersions of CARV with the selected (co)polymers (polyvinylpyrrolidone(PVP), hydroxypropyl methylcellulose (HPMC), Soluplus® and Eudragit®) were obtained.. Properties of the prepared CARV-polymer dispersions were observed by the polarizing and scanning electron microscopy and analyzed by differential scanning calorimetry and Fourier transform infrared spectroscopy. CARV was additionally characterized by X-ray powder diffraction. Furthermore, in vitro dissolution studies and dynamic compaction analysis were performed on the selected samples of solid dispersions. Among the studied polymers, PVP and HPMC have been identified as polymers with the highest affinity towards CARV, based on the calculated δp values. This has been also confirmed with the highest dissolution efficiency of CARV-PVP and CARV-HPMC solid dispersions. Solid state characterization indicated that CARV was dispersed either molecularly, or in the amorphous form, depending on interactions with each polymer. Determination of CARV-PVP and CARV-HPMC mechanical properties revealed that CARV-PVP solid dispersion has superior compactibility and tabletability. Therefore, CARV-PVP solid dispersion has been highlighted as the most appropriate for the further development of tablets as the final dosage form. Presented study provides an example for efficient approach for development of poorly soluble drug solid dispersion with satisfactory tableting properties.

Up to 50% of Crohn's disease and ulcerative colitis patients suffer from ileo-colonic inflammation. Topically delivered budesonide is an effective treatment but in vitro as well as clinical data suggest that oral formulations currently used in clinical practice are not optimal to treat the ileo-colon. The aim of this in vitro study was to develop ileo-colonic-targeted zero-order sustained-release tablets containing 3 mg or 9 mg budesonide. Targeted delivery was achieved by coating the tablets with the ColoPulse technology (ColoPulse 3 mg or ColoPulse 9 mg, respectively). Tablet were tested in a 10-h gastrointestinal simulation system for site-specific release, zero-order release kinetics (R2≥0.950), release rate, and completeness of release (≥80%). Release profiles of the novel formulations were compared with Entocort, Budenofalk, and Cortiment (budesonide MMX). ColoPulse 3 mg and 9 mg were targeted to the simulated ileo-colon, budesonide release was complete and in a sustained zero-order manner, and both formulations complied with a 6-month accelerated stability study. None of the formulations currently used in clinical practice targeted the ileo-colon. These in vitro results are discussed in light of clinical data. ColoPulse 3 mg and 9 mg are novel interesting formulations for the treatment of the entire ileo-colon in inflammatory bowel disease.

Near-Infrared hyperspectral image (HSI-NIR) is a useful technique for pharmaceutical research and industry alike. It can provide important surface information such as the polymorphs quantification and its distribution over the tablet. Several chemometric tools are applied for this purpose, with MCR-ALS and PLS regression being the most common approaches. In this work, a detailed comparison between these two approaches are performed. Beyond a "simple" regression comparison, a comparison of the score images (local quantification) was also evaluated. The system under study is tablets with ternary mixtures of Mebendazol (MBZ) polymorphs, microcrystalline cellulose and magnesium stearate. PLS models, in general, gave lower RMSEP (below 1.7% w/w for the three MBZ polymorphs) than the corresponding MCR-ALS predictions. Analyzing the distributions of the scores in the images of each sample shows clear differences between the PLS and MCR-ALS models. The MCR-ALS gave more chemical meaningful distribution maps for all polymorphs, even though the PLS accurately predicts the average concentration across the image. The problem is that the PLS models used the main spectral regions to quantify each MBZ polymorph, but at the same time undermines the minor spectroscopic changes caused by the different polymorphs. Although this may seem as a minor deviation from the truth, the results clearly show that this deviation is detrimental for the analysis of the spatial distribution of the analytes. These results indicate that the optimal multivariate model for multivariate images depend on the goal of the analysis: global quantification or a distribution analysis.