Scale-up from batch to flow-through wet milling process for injectable depot formulation

Injectable depot formulations are aimed at providing long-term sustained release of a drug into systemic circulation, thus reducing plasma level fluctuations and improving patient compliance. The particle size distribution of the formulation in the form of suspension is a key parameter that controls the release rate. In this work, the process of wet stirred media milling (ball milling) of a poorly water-soluble substance has been investigated with two main aims: (i) to determine the parametric sensitivity of milling kinetics; and (ii) to develop scale-up methodology for process transfer from batch to flow-through arrangement. Ball milling experiments were performed in two types of ball mills, a batch mill with a 30ml maximum working volume, and a flow-through mill with a 250ml maximum working volume. Milling parameters were investigated in detail by methodologies of QbD to map the parametric space. Specifically, the effects of ball size, ball fill level, and rpm on the particle breakage kinetics were systematically investigated at both mills, with an additional parameter (flow-rate) in the case of the flow-through mill. The breakage rate was found to follow power-law kinetics with respect to dimensionless time, with an asymptotic d50 particle size in the range of 200-300nm. In the case of the flow-through mill, the number of theoretical passes through the mill was found to be an important scale-up parameter

Use of Vibrational Spectroscopic Techniques for the Characterization of Structured Particles for Chemical Robots

This work is aimed at utilization of vibrational spectroscopic techniques for characterization of several types of structural particles suitable for the construction of chemical robots. Several case studies are presented and discussed: (i) PNIPAM-coated silica particles, (ii) surface-functionalized magnetic nanoparticles modified by citric and oleic acid, (iii) nanocomposit SERS-active substrates consisting of self-assembled monolayers of linear α,ω-aliphatic diammines with different lengths on Ag metal surface and a flat Ag electrode followed by testing of sensing activity of AD/NPs systems in the detection of the pesticide aldrin. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/3515

The combined use of imaging approaches to assess drug release from multicomponent solid dispersions

PURPOSE: Imaging methods were used as tools to provide an understanding of phenomena that occur during dissolution experiments, and ultimately to select the best ratio of two polymers in a matrix in terms of enhancement of the dissolution rate and prevention of crystallization during dissolution. METHODS: Magnetic resonance imaging, ATR-FTIR spectroscopic imaging and Raman mapping have been used to study the release mechanism of a poorly water soluble drug, aprepitant, from multicomponent amorphous solid dispersions. Solid dispersions were prepared based on the combination of two selected polymers - Soluplus, as a solubilizer, and PVP, as a dissolution enhancer. Formulations were prepared in a ratio of Soluplus:PVP 1:10, 1:5, 1:3, and 1:1, in order to obtain favorable properties of the polymer carrier. RESULTS: The crystallization of aprepitant during dissolution has occurred to a varying degree in the polymer ratios 1:10, 1:5, and 1:3, but the increasing presence of Soluplus in the formulation delayed the onset of crystallization. The Soluplus:PVP 1:1 solid dispersion proved to be the best matrix studied, combining the abilities of both polymers in a synergistic manner. CONCLUSIONS: Aprepitant dissolution rate has been significantly enhanced. This study highlights the benefits of combining imaging methods in order to understand the release process

Ultramafic vegetation and soils in the circumboreal region of the Northern Hemisphere

The paper summarizes literature on climate, soil chemistry, vegetation and metal accumulation by plants found on ultramafic substrata in the circumboreal zone (sensu Takhtajan, Floristic regions of the world, 1986) of the Northern Hemisphere. We present a list of 50 endemic species and 18 ecotypes obligate to ultramafic soils from the circumboreal region of Holarctic, as well as 30 and 2 species of Ni and Zn hyperaccumulators, respectively. The number of both endemics and hyperaccumulators are markedly lower compared to that of the Mediterranean and tropical regions. The diversity of plant communities on ultramafics soils of the circumboral region is also described. The underlying causes for the differences of ultramafic flora between arctic, cold, cool temperate and Mediterranean and tropical regions are also discussed. © 2018, The Ecological Society of Japan

The effect of adsorbent characteristics on the performance of a continuous sorption-enhanced steam methane reforming process

The steam methane reforming (SMR) process for hydrogen production with in situ CO2 capture on adsorbent particles pneumatically conveyed through a monolithic catalytic reactor and subsequently regenerated ex situ, was considered. A mathematical model has been formulated, based on differential mass and energy balances in the reactor and the regenerator, Langmuir isotherm for CO2 sorption equilibrium, the linear driving force approximation for sorption kinetics, and literature values for the kinetics of the three main SMR reactions. The effect of the adsorbent characteristics-the maximum CO2 capacity and the sorption kinetics-on the overall process performance in terms of methane conversion and CO2 separation has been systematically investigated in a parametric study. The main conclusions of the study are that: (i) conversion enhancement and CO2 recovery show a strongly non-linear dependence on both sorption capacity and kinetics; (ii) comparable conversion enhancement and CO2 recovery can be achieved by means of both lithium zirconite-like (high capacity, slow kinetics) and hydrotalcite-like (low capacity, fast kinetics) adsorbents; (iii) if an ideal adsorbent possessing hydrotalcite-like sorption kinetics and zirconite-like capacity were developed, the conversion enhancement factor could be more than doubled and a nearly 100% CO2 recovery could be achieved under otherwise identical conditions. © 2007 Elsevier Ltd. All rights reserved