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Purpose: Twin screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to continuous granulation of moisture sensitive drugs. However, knowledge of the material behavior during TS HMG is crucial to optimize the formulation, process and resulting granule properties. The aim of this study was to evaluate the agglomeration mechanism during TS HMG using a rheometer in combination with differential scanning calorimetry (DSC). Methods: An immiscible drug-binder formulation (caffeine-Soluplus) was granulated via TS HMG in combination with thermal and rheological analysis (conventional and Rheoscope), granule characterization and Near Infrared chemical imaging (NIR-CI). Results: A thin binder layer with restricted mobility was formed on the surface of the drug particles during granulation and is covered by a second layer with improved mobility when the Soluplus concentration exceeded 15% ( w/ w). The formation of this second layer was facilitated at elevated granulation temperatures and resulted in smaller and more spherical granules. Conclusion: The combination of thermal and rheological analysis and NIR-CI images was advantageous to develop in-depth understanding of the agglomeration mechanism during continuous TS HMG and provided insight in the granule properties as function of process temperature and binder concentration. [ABSTRACT FROM AUTHOR]

Twin screw hot melt granulation (TSHMG) is an innovative and continuous drug formulation process allowing granulation of moisture sensitive drugs. However, due to the lack of experience and in-depth process understanding, this technique is not yet widely used. During the TSHMG process, the microstructure of the granules is generated and modified and strongly depends on the flow behavior of the material. Hence, rheology might be a suitable tool to simulate and examine this process. However, chemical interactions of the material are influencing the physical properties leading to the microstructure. In this research project it is spectroscopically investigated whether the heat applied in a rheometer induces the same molecular effects as these occurring during TSHMG of the model formulation caffeine anhydrous/Soluplus®. Hence, it is evaluated whether rheology can be used as a simulation tool to improve the understanding of the material behavior at molecular level during continuous melt granulation. Therefore, in-line Raman spectroscopy is executed during TSHMG and in situ Fourier Transform Infra-red (FTIR) during oscillatory rheological experiments. The results from the in-line Raman monitoring revealed polymorph transition of caffeine anhydrous during twin screw melt granulation with Soluplus® which is stimulated depending on the binder concentration and/or granulation temperature. A correlation was seen between the FTIR spectra obtained during the rheological temperature ramp and the in-line collected Raman spectra during the melt granulation runs. The polymorphic conversion of caffeine anhydrous could be detected in the same temperature range with both techniques, proving the comparability of plate–plate rheometry and hot melt granulation (HMG) for this case with the used parameter settings. Process simulation using rheology combined with in situ FTIR seems a promising approach to increase process understanding and to facilitate binder and parameter selection for TSHMG. [ABSTRACT FROM AUTHOR]

The objective of this project was to investigate the potential of Kleptose Linecaps DE17 (KLD) in masking the unpleasant/bitter taste of therapeutic agents by hot melt extrusion (HME). Griseofulvin (GRI) and caffeine anhydrous (CA) were used as a bitter active pharmaceutical ingredient (API) model drugs. Thermogravimetric studies confirmed the stability of GRI, CA, and KLD at the employed extrusion temperatures. The differential scanning calorimetry (DSC) studies revealed a characteristic melting endotherm of GRI at 218-220°C and CA at 230-232°C in the physical mixtures as well as in all extrudates over the period of study, indicating the crystalline nature of drug. HME of KLD was achieved only in the presence of plasticizer. Among the several plasticizers investigated, xylitol showed improved processability of KLD at 15% w/ w concentration. Dissolution studies of HME extrudates using simulated salivary medium exhibited ∼threefold less release compared to physical mixture at the end of 5 min (the lesser drug release, better the taste masking efficiency). Furthermore, the results from the sensory evaluation of products in human panel demonstrated strong bitter taste in the case of physical mixture compared to the HME formulation, suggesting the potential of Kleptose Linecaps DE17 as taste masking polymer in melt extruded form. [ABSTRACT FROM AUTHOR]

The effects of caffeine were investigated in judo, boxing, taekwondo and Brazilian jiu-jitsu. However, this substance was never investigated regarding traditional jiu-jitsu. Therefore, the aim of this research was to analyze the effects of caffeine in the Special Judo Fitness Test (SJFT) and technical variables during combat in traditional jiu-jitsu elite athletes. Methods: Twenty-two young professionals of traditional jiu-jitsu, 11 men and 11 women (age = 22 ± 4 (18–33) years, body mass = 66.6 ± 10.8 (46.2–86.1) kg, height = 1.70 ± 0.9 (1.55–1.85) m) with 15 ± 7 years of experience in traditional jiu-jitsu, participated in a double-blind, counterbalanced, crossover study. In two different conditions, the traditional jiu-jitsu athletes ingested 3 mg/kg body mass of caffeine or a placebo. After 60 min, they performed the SJFT test to measure throwing performance, and subsequently, combat to analyze offensive and defensive hitting techniques. Results: Caffeine had a main effect on the number of throws during the SJFT test (P < 0.01). In addition, it was effective in sets 2 (13 ± 2 vs. 14 ± 2; p = 0.01) and 3 (12 ± 2 vs. 13 ± 1; p = 0.03). There was also a main effect during the test on heart rate when caffeine was ingested (F = 12.48, p < 0.01). The effects of caffeine were similar compared to the placebo condition regarding performance during combat both in offensive and defensive fighting variables Conclusions: the pre-exercise ingestion of 3 mg/kg body mass of caffeine increased performance in the SJFT test, decreased fatigue perception, and increased power and endurance perception in professionally traditional jiu-jitsu athletes. However, it did not seem to improve offensive and defensive technical actions during combat. [ABSTRACT FROM AUTHOR]