In order to introduce a cost-effective strategy method for commercial scale dry granulation at the early clinical stage of drug product development, we developed dry granulation process using formulation without API, fitted and optimized the process parameters adopted Design of Experiment (DOE). Then, the process parameters were confirmed using one formulation containing active pharmaceutical ingredient (API). The results showed that the roller pressure had significant effect on particle ratio (retained up to #60 mesh screen), bulk density and tapped density. The roller gap had significant influence on particle ratio and specific energy. The particle ratio was significantly affected by the mill speed (second level). The tabletability of the powder decreased after dry granulation. The effect of magnesium stearate on the tabletability was significant. In the process validation study, the properties of the prepared granules met the requirements for each response studied in the DOE. The prepared tablets showed higher tensile strength, good content uniformity of filled capsules, and the dissolution profiles of which were consistent with that of clinical products. This drug product process development and research strategies could be used as a preliminary experiment for the dry granulation process in the early clinical stage.

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Spices are usually ground for applications and the resulting particle size of the powders is an important product attribute in view of the release of flavour. However, inhomogeneity of the original material may lead to variations in the physicochemical characteristics of the particles. This variation and its linkage to particle size may be examined by particular imaging techniques. This study aimed to explore the potential of Fluorescence Lifetime Imaging Microscopy (FLIM) to characterize spice powders according to particle size variations and correlation with their pigment contents to reveal the chemical information contained within the FLIM data. Ginger powder was used as a representative powder model. The FLIM profiles of the individual samples and populations revealed that FLIM coupled with the phasor approach has the capacity to characterize spice powder according to particle size. Meanwhile, Principal Component Analysis of pre-processed FLIM data revealed clustering of particle size groups. Further correlation analysis between the pigment compound contents and FLIM data of the ginger powders indicated that FLIM reflected chemical information of ginger powder and was able to visualize endogenous fluorophores. The current study revealed the potential of FLIM to characterize ginger powder particles. This approach may be extrapolated to other spice powder products. The new knowledge is a step further in paving the way for the application of innovative techniques, already prevalent in other domains, to food quality and authentication.

Talc is used in cosmetic products to confer desirable properties, such as moisture absorption and smooth texture, to the finished products. Concerns have been raised about the potential presence of asbestos in products containing cosmetic talc. Reconstruction of potential asbestos exposure from the use of cosmetic talc products (assuming a trace level of asbestos) requires consideration of consumer use patterns. Although application generally only lasts seconds, exposure theoretically may continue if the consumer remains in the immediate vicinity. Most published exposure measurements have not adequately characterized the potential for continued exposure. In this analysis, estimates and measurements of airborne asbestos fiber concentrations associated with cosmetic talc use from 10 published studies were used as inputs to an exponential decay model to estimate \"worst-case\" exposure during and following application. The resulting geometric mean 30-min time-weighted average (TWA) concentrations were 0.006 f/cc for both puff and shaker application, for diapering, 0.0001 f/cc (adult applying baby powder) and 0.0002 f/cc (infant), and for makeup application, 0.0005 f/cc. Application of an exponential decay model to measured or estimated asbestos concentrations associated with the use of cosmetic talc products yields a conservative means to comprehensively reconstruct such exposures. Moreover, our results support that, if a cosmetic talc powder product contained a trace level of asbestos fibers, the \"worst-case\" airborne asbestos exposure associated with its application is low.

Twin-screw wet granulation is an emerging continuous manufacturing technology for solid oral dosage forms. This technology has been successfully employed for the commercial manufacture of immediate-released tablets. However, the higher polymer content in extended-release (ER) formulations may present challenges in developing and operating within a desired design space. The work described here used a systematic approach for defining the optimum design space by understanding the effects of the screw design, operating parameters, and their interactions on the critical characteristics of granules and ER tablets. The impacts of screw speed, powder feeding rate, and the number of kneading (KEs) and sizing elements on granules and tablets characteristics were investigated by employing a definitive screening design. A semi-mechanistic model was used to calculate the residence time distribution parameters and validated using the tracers. The results showed that an increase in screw speed decreased the mean residence time of the material within the barrel, while an increase in the powder feeding rate or number of KEs did the opposite and increased the barrel residence time. Screw design and operating parameters affected the flow and bulk characteristics of granules. The screw speed was the most significant factor impacting the tablet\'s breaking strength. The dissolution profiles revealed that granule characteristics mainly influenced the early phase of drug release. This study demonstrated that a simultaneous optimization of both operating and screw design parameters was beneficial in producing ER granules and tablets of desired performance characteristics while mitigating any failure risks, such as swelling during processing.

The influence of partial crystallinity on the structural relaxation behavior of low-molecular organic glasses is, contrary to, e.g., polymeric materials, a largely unexplored territory. In the present study, differential scanning calorimetry was used to prepare a series of amorphous indomethacin powders crystallized to various extents. The preparations stemmed from the two distinct particle size fractions: 50-125 µm and 300-500 µm. The structural relaxation data from the cyclic calorimetric measurements were described in terms of the phenomenological Tool-Narayanaswamy-Moynihan model. For the 300-500 µm powder, the crystalline phase forming dominantly on the surface led to a monotonous decrease in the glass transition by ~6 °C in the 0-70% crystallinity range. The activation energy of the relaxation motions and the degree of heterogeneity within the relaxing matrix were not influenced by the increasing crystallinity, while the interconnectivity slightly increased. This behavior was attributed to the release of the quenched-in stresses and to the consequent slight increase in the structural interconnectivity. For the 50-125 µm powder, distinctly different relaxation dynamics were observed. This leads to a conclusion that the crystalline phase grows throughout the bulk glassy matrix along the internal micro-cracks. At higher crystallinity, a sharp increase in Tg, an increase in interconnectivity, and an increase in the variability of structural units engaged in the relaxation motions were observed.

Mini-tablets (MTs) with losartan potassium were developed to treat the rare disease Epidermolysis Bullosa. The focus was placed on transfer and scale-up of a direct compressible formulation from the compaction simulator STYL\'One Evo (CS) to the rotary tablet press Korsch XM 12 (RP). Transfer of tabletability and compactibility profiles from CS to RP did not show good agreement, e.g. at a tableting pressure of 125 MPa mean tensile strengths (TS) of 4 MPa on CS and 1-1.5 MPa on RP were reached. These results highlight the impact of the feed frame on final product qualities depending on process and material factors. In the scale-up studies the critical quality attributes (CQAs) mass variation, content uniformity, TS and disintegration time were investigated. After an appropriate run-up time, most CQAs reached a plateau, after reaching a balance between influx, efflux and distribution of lubricant in the feed frame. TS values of 1-2 MPa, disintegration times of max. 50 s, mass variation of 0.9-2.2 % (CV) and acceptance values below 15.0 were reached depending on chosen process parameters.

BACKGROUND: Sour cherry juice concentrate powder can serve as a modern, easy-to-handle, phenolics-rich merchandise; however, its transformation into powdered form requires the addition of carriers. In line with the latest trends in food technology, this study valorizes the use of dairy by-products (whey protein concentrate, whey, buttermilk, and mixes with maltodextrin) as carriers. A new multiple approach for higher drying yield, phenolics retention (phenolic acids, flavonols and anthocyanins) and antioxidant capacity of powders were tested as an effect of simultaneous decrease of drying temperature due to the drying air dehumidification and lower carrier content.
RESULTS: Dairy-based carriers were effective for spray drying of sour cherry-juice concentrate. The drying yield was increased and retention of phenolics was higher when compared with maltodextrin. The application of dehumidified air, which enabled the drying temperature to be reduced, affected drying yield positively, and also affected particle morphology and retention of phenolics (the phenolic content was approximately 30% higher than with spray drying).
CONCLUSIONS: The study proved that it is possible to apply dairy-based by-products to produce sour cherry juice concentrate powders profitably, lowering the spray-drying temperature and changing the carrier content. Dehumidified air spray drying can be recommended for the production of fruit juice concentrate powders with improved physicochemical properties. © 2023 Society of Chemical Industry.

As one of derivatives of Vitamin B12, methylcobalamin (MeCbl) is an indispensable \"Life Element\" and plays an essential role in maintaining human normal physiology function and clinical medicine application. Because of the intricate molecular structure, strong hygroscopicity and optical instability, maintaining its solid stability is a great challenge in pharmaceutical preparation. Based on the structure features of MeCbl hydrates, this study explored the drug solid stability by designing solid-solid phase transformation (SSPT) experiments. Three hydrate powders of MeCbl that had special structure with isolated site and channel water molecules were discovered. It was found that drying condition and surrounding humidity were controlling factors influencing the final solid form. The inter-conversion relations relevant to heating-induced and humidity-induced structure changes were established among the three hydrate powders. Powder X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, high performance liquid chromatography and dynamic vapor sorption were used to characterize the differences and related properties of stably prepared MeCbl hydrate powders. The particle size of product could be regulated and controlled by optimizing operating conditions of crystallization process, where ultrasound-assisted and seeding-introduced were applied as promising strategies to enhance solution crystallization process. This study opens up the possibility for the stable preparation and large-scale production of polycyclic macromolecular bulk drugs like methylcobalamin.

Nutmeg is an inexpensive, readily available spice used in a variety of recipes. However, the use of nutmeg powder as a recreational drug for its hallucinogenic effects is resulting in an increase in overdose rates. We encountered a male patient being hospitalized after ingesting 75 g of commercially available nutmeg powder with the intent of committing suicide. There are no available reports documenting the toxic or comatose-fatal blood concentrations or time-course of drug action in cases of nutmeg poisoning. Therefore, to improve patient management, we endeavored to determine the blood serum levels and time-course of the major psychoactive compounds (safrole, myristicin, and elemicin) present in nutmeg. We designed a simple and reliable method using the MonoSpin® extraction kit and gas chromatography-tandem mass spectrometry to detect the presence of these psychoactive compounds in human serum. The method had detection and quantitation limits of 0.14-0.16 and 0.5 ng/mL (lowest calibration points), respectively. The calibration curves displayed excellent linearity (0.996-0.997) for all three compounds at 0.5-300 ng/mL blood concentrations. The intra- and inter-day precision values for quality assurance were in the ranges of 2.4-11 % and 2.5-11 %, respectively; bias ranged from - 2.6 % to 2.1 %. Blood serum levels of safrole, myristicin, and elemicin were measured at admission (approximately 8 h post-ingestion) and approximately 94 h after a post-admission fluid therapy to evaluate their biological half-lives. We developed this method to obtain information on the psychoactive constituents of nutmeg and, thereby, determine the toxicokinetic parameters of nutmeg in a case of nutmeg poisoning.