Search Results (8)

Solid crystalline suspensions (SCSs) containing submicron particles were introduced as a competitive solution to increase dissolution rates and the bioavailability of poorly water-soluble drugs. In an SCS, poorly water-soluble drug crystals are finely dispersed in a hydrophilic matrix. Lately, melt milling as an adapted wet milling process at elevated temperatures has been introduced as a suitable batch manufacturing process for such a formulation. In this work, the transfer from batch operation to a two-step continuous process is demonstrated to highlight the potential of this technology as an alternative to other dissolution-enhancing methods. In the first step, a powder mixture of a model drug (griseofulvin) and a carrier (xylitol) is fed to an extruder, where a uniform suspension is obtained. In the second step, the suspension is transferred to a custom-built annular gap mill, where comminution down to the submicron region takes place. The prototype’s design was based on batch grinding results and a narrow residence time distribution, intended to deliver large quantities of submicron particles in the SCS. The throughput of the mill was found to be limited by grinding media compression. By inclining the mill at an angle, the grinding media position was manipulated, such that compression was avoided. Different states of the grinding media in the grinding chamber were identified under surrogate conditions. This strategy allows the maintenance of an energy-optimized comminution without adaption of the associated process parameters, even at high throughputs. Using this new process, the production of an SCS with 80–90 % submicron particles in a single passthrough was demonstrated. Full article

Sample homogeneity dictates whether analyzing a test portion of an entire sample can provide representative information about incurred mycotoxins. In this study, we evaluated particle-size-distribution-based homogeneity of laboratory mycotoxin samples using laser diffraction particle size analysis and International Organization for Standardization (ISO) Guide 35: 2017. Incurred whole corn, compound feed, peanut butter, and wheat flour (500 g each) were comminuted using wet, cryogenic, or dry milling. We used a sample dividing (riffling) device to obtain representative subsamples (25 g each) and developed a laser diffraction particle size analysis procedure by optimizing key parameters such as the refractive index, absorption, and stirring rate. The homogeneity of the particle size distribution within laboratory subsamples was characterized using the optimized laser diffraction procedure. An assessment of homogeneity was also performed for individual mycotoxins in each incurred matrix sample following the procedure described in ISO Guide 35. The concentrations of the incurred mycotoxins were determined using liquid chromatography–mass spectrometry (LC-MS). Within- and between-subsample variances of incurred aflatoxin B1 in peanut butter; deoxynivalenol in corn, compound feed, and wheat flour; and fumonisins in compound feed corroborated that when the particle size measurements were less than 850 µm, mycotoxins concentrations were consistent across independent test portions, which was confirmed using an analysis of variance (F-test). This study highlights the benefits of laser diffraction particle size analysis and suggests its use as a test procedure to evaluate homogeneity in new sample commodities. Full article

This study presents an approach for targeted comminution of component mixtures within a wet-operated stirred media mill. In the first step, a general understanding of the interactions between individual components on the grinding result with mixtures could be gained with basic experiments and following our former research work. In particular, a protective effect of the coarser particles on the fines could be elucidated. These findings were used to develop a process for the production of a battery slurry containing fine ground silicon particles as well as dispersed carbon black and graphite particles. By a tailored sample preparation applying a combination of particle dissolution and separation, the particle size distributions of carbon black and graphite particles were analyzed separately within the produced battery slurries. Based on the selective particle size analysis, the slurry preparation could be transferred from a complex multistage batch process using a dissolver to a stirred media mill, which was finally operated in a continuous one-passage mode. The prepared slurries were subsequently further processed to silicon-rich anodes using a pilot scale coating and drying plant. Afterward, the produced anodes were electrochemically characterized in full cells. The cell results prove a comparable electrochemical behavior of anode coatings derived from a dissolver- or mill-based slurry production process. Therefore, we could demonstrate that it is possible to integrate the mixing process for the production of multicomponent slurries into the comminution process for the preparation of individual materials upstream. Even with nearly identical starting sizes of their feed materials, the targeted particle size distributions of the single components can be reached, taking into account the different material-dependent particle strengths and sequential addition of single components to the multicomponent comminution process. Full article

Amorphous solid dispersions (ASD) are one of the most prominent formulation approaches to overcome bioavailability issues that are often presented by new poorly soluble drug candidates. State-of-the art manufacturing techniques include hot melt extrusion and solvent-based methods like spray drying. The high thermal and mechanical shear stress during hot melt extrusion, or the use of an organic solvent during solvent-based methods, are examples of clear drawbacks for those methods, limiting their applicability for certain systems. In this work a novel process technology is introduced, called Nano-Dry-Melting (NDM), which can provide an alternative option for ASD manufacturing. NDM consists of a comminution step in which the drug is ground to nanosize and a drying step provides a complete amorphization of the system at temperatures below the melting point. Two drug–polymer systems were prepared using NDM with a wet media mill and a spray dryer and analyzed regarding their degree of crystallinity using XRD analysis. Feasibility studies were performed with indomethacin and PVP. Furthermore, a “proof-of-concept” study was conducted with niclosamide. The experiments successfully led to amorphous samples at temperatures of about 50 K below the melting point within seconds of heat exposition. With this novel, solvent-free and therefore “green” production technology it is feasible to manufacture ASDs even with those drug candidates that cannot be processed by conventional process technologies. Full article

Within this contribution, the effect of grinding media wear on the melt crystallisation of polybutylene terephthalate (PBT) is addressed. PBT was wet ground in a stirred media mill in ethanol using different grinding media beads (silica, chrome steel, cerium-stabilised and yttrium-stabilised zirconia) at comparable stress energies with the intention to use the obtained particles as feed materials for the production of feedstocks for laser powder bed fusion additive manufacturing (PBF-AM). In PBF‑AM, the feedstock’s optical, rheological and especially thermal properties—including melt crystallisation kinetics—strongly influence the processability and properties of the manufactured parts. The influence of process parameters and used grinding media during wet comminution on the optical properties, crystal structure, molar mass distribution, inorganic content (wear) and thermal properties of the obtained powders is discussed. A grinding media-dependent acceleration of the melt crystallisation could be attributed to wear particles serving as nuclei for heterogeneous crystallisation. Yttrium-stabilised zirconia grinding beads proved to be the most suitable for the production of polymer powders for the PBF process in terms of (fast) comminution kinetics, unchanged optical properties and the least accelerated crystallisation kinetics. Full article

In this study, two methods based on the use of diluted acids were developed: microwave-assisted wet digestion (MAWD) and microwave-assisted ultraviolet digestion (MAWD-UV). These methods are evaluated for the digestion of oral pharmaceutical drugs and further determination of elemental impurities from classes 1 (As, Cd, Hg and Pb) and 2A (Co, Ni and V) by inductively coupled plasma optical emission spectrometry (ICP-OES). Commercial drugs for the treatment of type 2 diabetes are used. No prior comminution is performed. For MAWD, the optimized conditions were 2 mol L⁻¹ or 3 mol L⁻¹ HNO₃, 1 mL of 50% H₂O₂ and a 45 min or 55 min irradiation program. For MAWD-UV, the condition using 1 mol L⁻¹ HNO₃, 1.6 mL of 50% H₂O₂ and a 55 min irradiation program enabled the digestion of all samples. In this way, efficient methods are proposed for the digestion of commercial pharmaceutical tablets for further determination of class 1 and 2A elemental impurities (ICH Q3D guidelines). Full article

Preparation of nanocrystal formulations by wet media milling and spray-drying is a reliable technique to enhance dissolution and ameliorate absorption limitations of poorly soluble BCS II drugs. However, when thermosensitive compositions are dried at high temperatures, the risks of particle aggregation and thermal degradation must be considered. The present study investigates the effects of nanosuspension formulation variables when performing the spray drying process at equidistant temperatures above and below the melting point. Towards this purpose, Fenofibrate is exploited as a model drug of unfavorable pharmacokinetic profile and low melting point (79–82 °C), properties that render thermal processing a nontrivial task. Rationalizing the system’s behavior by combining molecular simulations with QbD methodology, the preparation of stable nanocrystals can be “steered” in order to avoid undesirable melting. The statistically resolved operational conditions showed that Fenofibrate Critical Quality Attribute–compliant nanosuspensions i.e., bearing hydrodynamic diameter and ζ-potential of 887 nm and −16.49 mV, respectively, were obtained by wet milling drug to Pharmacoat and mannitol weighted optimum ratios of 4.075% and 0.75%, after spray drying at the desired temperature of 77 °C. In conclusion, we present a quality assurance methodology of nano-comminution generally applicable for thermo-labile BCS II drugs. Full article

Comparison of dry and wet grinding process in an electromagnetic mill is presented in this paper. The research was conducted in a batch copper ore grinding. Batch mode allows for precise parametrization and constant repetitive conditions of the experiments. The following key aspects were tested: processing time, feed size, size of the grinding media, mass of the material and graining media, and density of the pulp. The particles size distribution of the product samples was analyzed in the laboratory after each experiment. The paper discusses the experimental results as well as the concept of dry and wet grinding and classification circuits for the electromagnetic mill. The main points of the discussion are the size reduction effectiveness and power consumption of the entire system. Full article