Bulk Powder Research Articles

Mechanism for improving the dissolution rate of poorly soluble acidic drugs using poly-γ-glutamic acid and the formulation of poly-γ-glutamic acid-coated particles to improve dissolution rate

For poorly soluble drugs, formulations designed to improve their solubility are needed in order to ensure effective blood concentrations are achieved after oral administration. In this study, we developed a new solubilization method for poorly soluble acidic drugs using poly-γ-glutamic acid (PGA). The drugs were released from drug/PGA mixed powders more rapidly than from drug bulk powders. This rapid drug release was thought to be due to molecular interactions between PGA and the drugs when they were dissolving. From these results, it was considered that PGA-coated drug particles were useful for improving the dissolution rate of the drug. PGA-coated drug particles were prepared using indomethacin and warfarin, and rapid drug release from the PGA-coated drug particles was confirmed. The optimum amount of PGA for drug coating was examined, and it was suggested that acceptable particles may be prepared by adding 50 mg PGA potassium salt to 100 mg of drug.

Characterization of Boswellia rivae Engl Resin as a Potential Use for Pharmaceutical Excipient.

Pharmaceutical excipients derived from natural sources like resins are nowadays meritoriously used in the formulation of drugs. Resins of natural origin have many advantages over chemically synthesized substances; they are safer, nontoxic, less expensive, biodegradable, and widely available. To our knowledge, resins from plants have been not sufficiently explored for application in pharmaceutical formulations. Thus, in the present study, a resin isolated from Boswellia rivae Engl was characterized for its potential use as a pharmaceutical excipient. Method. The resin was extracted from the oleo gum resin of Boswellia rivae Engl, which involved the removal of volatile oils, gum, and Boswellic acid contents. The dried resin powder was then characterized for its micromeritic properties, heavy metal contents, moisture content, moisture absorption power, pH, solubility, swelling property, and acute toxicity profile. Moreover, the crystal nature and the chemical functionality of the resin were evaluated by using X-ray diffraction and Fourier transform infrared spectrometry, respectively. Results. The yield of the neutral resin was 13.17%, and the powder was pale yellow and had irregular surfaces. The resin was freely soluble in organic solvents but almost insoluble in water. The moisture content of the dried extract was 2.5% while its moisture absorption capacity was 2.5%, 4%, and 5.47% at 40%, 60%, and 75% RH, respectively. Besides, the maximum swelling capacities of the resin observed were 40%, 37%, and 30% at 350C, 300C, and 250C, respectively. The bulk powder exhibited a 1.21 Hausner ratio, 36.497 angles of repose, and 17.03% Carr's index, indicating the fair flowability of the powder. Heavy metals such as zinc, chromium, and cobalt were detected at a low level while elements like copper, manganese, lead, and cadmium were absent. The X-ray diffraction study revealed that the crystallinity index of the powder was 42.7% with a crystal size of 994.5A. The Boswellia resin could be safe in mice up to 3 g/kg of their body weight. In conclusion, the physicochemical properties of the resin powder investigated reveal its potential application as pharmaceutical additives in the formulation of modified release solid dosages forms like tablets and microcapsules.

Aeration and cohesive effects on flowability in a vibrating powder conveyor

A CFD-DEM model for aerated vibratory convection was developed to explore the coupled gas-solid interactions governing bulk powder bed dynamics. Each simulation was prepared by carefully characterizing the rough, porous conveyor baseplate and four candidate particle sizes representative of typical powder beds. Trends in the vibratory convection of particles between 20 and 250 μm in diameter could be explained by considering each powder's minimum fluidization velocity and the magnitude of van der Waals cohesive forces. Simulations of fine powders under high cohesive forces exhibited competing effects from drag and cohesion; drag promotes powder-frit liftoff while cohesion suppresses contact separation. Experimental convection velocities were observed to be in good agreement with the simulated mean powder velocity for throw numbers between 0.25 and 0.50.

Innovative Investigation of Zinc Oxide Nanoparticles Used in Dentistry

Dental caries is a major lifestyle concern as dental components affect the face of an individual. The issue of tooth decay occurs in every age group throughout the globe. Researchers are probing incipient implements and techniques to develop filling agents for decayed teeth. Zinc oxide (ZnO) powder is utilized mostly as a filling agent. Nanotechnology enhanced the efficiency of compounds of metal oxides utilized for dental caries. The present study aims to investigate the properties of ZnO nanoparticles (NPs) synthesized chemically (using ZnCl2 and NaOH) as well as biologically (using aqueous leaf extract of Murraya paniculata). The XRD patterns confirm that ZnO NPs have a hexagonal crystalline structure with particle sizes of 47 nm and 55 nm for chemically and biologically synthesized NPs, respectively. The FE-SEM data confirm the nanorod and spherical/cubical shape morphologies for the chemically and biologically synthesized ZnO NPs, respectively. FTIR data show the peaks between 4000 and 450 cm−1 of the functional groups of –OH, C-O, –C-H-, and Zn-O bonds. The UV–Vis absorption study indicates a peak around 370 nm and a hump around 360 nm corresponding to the chemically and biologically synthesized ZnO NPs, respectively. An antibacterial bioassay was performed and compared with commercially available ZnO bulk powder against tooth decaying pathogens, viz., Streptococcus mutans, Staphylococcus aureus, E. coli, and Lactobacillus fermentum, and found that both ZnO NPs had results closer to those of the standard drug (rifampicin). Thus, the synthesized ZnO NPs may be utilized as nano-drugs for the application of tooth decaying filling agents. Even biologically synthesized ZnO NPs may be considered more environmentally friendly and less toxic to human health concerns.

Vapor-Phase Adsorption of Xylene Isomers and Ethylbenzene in MOF-74 Thin Films.

Thin films of Co-MOF-74 and Ni-MOF-74 were synthesized on Au-coated quartz crystal microbalance substrates by a vapor-assisted conversion (VAC) method that precludes the need for activation via postsynthetic solvent exchange. All thin films were structurally characterized by powder X-ray diffraction, reflection-absorption infrared spectroscopy, and Raman spectroscopy. Scanning electron microscopy (SEM) images reveal that the Ni-MOF-74 films exists as a dense base layer with hemispherical protrusions on the surface. In contrast, the scanning electron microscopy images of the Co-MOF-74 thin films show a rough surface with spherical deposits. The thin film morphologies were different than the powders resulting from the bulk synthesis. Gravimetric vapor-phase adsorption measurements for xylene isomers and ethylbenzene within Co-MOF-74 and Ni-MOF-74 thin films were conducted, and the results were compared with those reported for the corresponding bulk powders. Despite different morphologies, the saturation capacities of Ni-MOF-74 and Co-MOF-74 thin films were found to be nearly equivalent to those reported for the bulk powders. The results demonstrate that the VAC method can produce MOF-74 thin films that retain the intrinsic properties that are observed in bulk powders.

Geochemistry of lunar meteorite Northwest Africa 11962 and its potential source region/crater in the Procellarum KREEP terrane

AbstractLunar meteorite Northwest Africa (NWA) 11962 is a regolith breccia with a diverse range of mineral and lithic clasts. For the present study, major and trace element contents and selected isotopic compositions were determined on a homogenized bulk powder of NWA 11962 by instrumental neutron activation analysis, thermal ionization mass spectrometry, and inductively coupled plasma mass spectrometry. The chemical composition of the sample points toward an origin of the meteorite from within the Procellarum KREEP terrane (PKT). Samarium‐Nd and Rb‐Sr isotopic compositions and concentrations show a similarity to those of Apollo 15 soils and KREEP basalt. Highly siderophile element (HSE) abundances and ratios, as well as the Re/Os isotopic system, are often used as tracers of different impactor types. The 187Os/188Os and 187Re/188Os isotopic ratios are within the range of ordinary chondrites, yet some of the siderophile element and highly siderophile element ratios are comparable to those of iron meteorites. Using Fe, Th, and Ti abundances of lunar surface regolith, measured by the Lunar Prospector gamma‐ray spectrometer, we attempt to constrain potential lunar source regions for NWA 11962. By matching these possible source regions with coordinates of recently (<1 Ma) formed lunar impact craters (so‐called lunar cold spots), we localized a potential source crater of NWA 11962 at the western rim of the PKT close to Sinus Medii.

Additive Manufacturing of Solid Products for Oral Drug Delivery Using Binder Jetting Three-Dimensional Printing

Binder jetting (BJ) three-dimensional (3D) printing is becoming an established additive manufacturing technology for manufacturing of solid products for oral drug delivery. Similar to traditional solutions based on compaction of powder mixture, successful processing of BJ products requires control of bulk powder properties. In contrast to traditional compaction-based process, BJ 3D printing allows for flexible modifications on microstructure, material composition and dose in the printed pharmaceutical products. Currently, systematic strategies for selecting excipients and optimizing the printing process have not been fully established. To address this challenge, a summary of the published work and selected patent literature around BJ 3D printing to fabricate pharmaceutical solid products for oral administration purposes is presented. First, an overview of characteristics of printed products as a part of the product design and a description of the commonly used excipients and active pharmaceutical ingredients is given. The critical powder and ink properties, as well as physical geometries and inner structures of a final product, are discussed in term of the mechanisms that determine the formation of a printed solid product and finally the quality of this product. This review is also summarizing the technical features of printers, printheads, and the critical considerations for post-processing procedures. BJ 3D printing is one of the most promising additive manufacturing technologies for mass customization of pharmaceutical products.

ЭКСПЕРИМЕНТАЛЬНОЕ ОПРЕДЕЛЕНИЕ ГИДРАВЛИЧЕСКОГО СОПРОТИВЛЕНИЯ УПРОЩЕННОЙ МОДЕЛИ МУЛЬТИВИХРЕВОГО КЛАССИФИКАТОРА С СООСНО РАСПОЛОЖЕННЫМИ ТРУБАМИ

An important task in the production of fine bulk material based on silica gel is to obtain a narrow fraction of the powder of the required dispersion. Existing devices, due to the required dispersion of bulk powder, technological and other parameters, do not always allow this to be done. The paper considers various classifiers. Their disadvantages for carrying out fractionation of bulk material based on silica gel at the Salavat Catalyst Plant are shown. The authors of the work proposed the design of a multi-vortex classifier for obtaining powder in size from 10 to 40 microns. The aim of this work is to obtain an experimental dependence of the hydraulic resistance of a simplified model of a multi-vortex classifier on the average velocity of the gas flow. 3 simplified models of the multi-vortex classifier are presented. The scheme of the experimental setup is presented. The method of conducting experiments is described. Based on the work carried out, the following conclusions were drawn. 1) Pressure losses in simplified models of a multi-vortex classifier range from 6 to 670.5 Pa at an input average gas flow velocity of 4.1 to 23.6 m/s. 2) The maximum hydraulic resistance corresponds to the first model with the largest number of local resistances - rectangular slots. 3) The equations of hydraulic resistance and coefficients of hydraulic resistance from the average velocity of the gas flow are obtained for 3 models of the multi-vortex classifier. 4) It is qualitatively obtained that there is a critical equivalent diameter of the inter-tube space, reflecting the beginning of the destruction of the vortex structure in the multi-vortex classifier. This factor leads to an increase in the hydraulic resistance of the device.

Design Considerations for Practical Li-S Battery Components for Electric Aviation

The development of high-energy, high-safety, and high-power batteries beyond electric automobile requirements is vital for future electric aviation applications. The transition to non-volatile solid-state electrolytes (SSE) promises many advantages over traditional flammable liquid electrolytes and may also be an enabling technology for next generation chemistries. However, significant manufacturing challenges must be overcome before the adoption of such technology. This study focuses on advancement of previous electrolyte development to produce sulfide-polymer composites with densified thicknesses between 20-30 microns using a tape-casting technique with an elastomer binder [1]. Parameters such as binder type, binder loading, and filler loading are modified to determine their impact on electrochemical performance and mechanical stability. The composites were determined to retain reasonable ionic conductivity with improved flexibility and scalability critical for practical manufacturing of such cells. Films were produced 10-15 times thinner than comparable bulk powder electrolytes and within the range of commercial polyolefin separators (25 micron) used in commercial liquid containing lithium-ion cells. Composite conductivities were maintained above 0.2mS/cm, which holds promise for future electric aviation applications. Processing techniques are investigated to further improve electrochemical performance.[1] Donald A. Dornbusch, Rocco P. Viggiano, John W. Connell, Yi Lin, Vadim F. Lvovich. Practical considerations in designing solid state Li-S cells for electric aviation, Electrochimica Acta, 2021, 139406, ISSN 0013-4686, https://doi.org/10.1016/j.electacta.2021.139406.

Thin Film Photodetectors Based on Zinc Oxide Nanoinks

Zinc oxide (ZnO) has many useful properties for electronics and optoelectronics including wide band gap, large exciton binding energy, low-cost, ease of processing and availability [1]. This has led to increased interest and development of thin film electronics, transparent conductors, solar cells, light-emitting diodes, lasers, photodetectors and various sensors based on ZnO materials [2, 3]. The high surface areas and tunable properties of ZnO nanostructures make them particularly suitable for applications such as sensing and photonic devices [4, 5].In this work, we present results on nanostructured ZnO thin film photodetectors fabricated using nanoparticle inks (nanoinks) obtained via planetary ball milling (PBM) of bulk powders. PBM [6] is an emerging solution-based nanofabrication approach that can quickly produce nanoink suspensions at low-cost by nanoscale grinding, without complex processing and suitable for thin film coating of various materials on different substrates [7]. The thin film photodetector devices were fabricated by depositing PBM ZnO nanoink onto flat insulating glass substrates followed by contact formation as shown schematically in Fig. 1a: PBM was performed using ZnO powder in ethylene glycol (EG) or deionized (DI) water solvent (a.k.a. colloidal grinding) with zirconia grinding beads. The grinding speed and time were varied between 200 and 1000 rpm and 10 min. and 60 min., respectively. A few μL of the resulting ZnO nanoink was used to coat the substrate surface and dried at ~ 100 °C. Lastly, two electrical contacts to the resulting films were made using silver paint and copper tape. Analysis of ZnO films after deposition showed they consist of nanostructured particles with sizes reaching below 100 nm, as displayed in the scanning electron microscopy (SEM) and atomic force microscopy (AFM) images in Fig. 1b, depending on grinding conditions (speed, time).The optical properties of the ZnO thin films were evaluated via photoluminescence measurements (Fig. 1c), which, in addition to interband transitions in the UV, displayed longer wavelength emission peaks due to surface and bulk defect states. Such deep level states are dependent on grinding parameters and thus allow the accessible spectrum for the nanostructured ZnO films to be extended into the visible region in a tunable manner. Two-terminal photoconductance data of the ZnO PBM nanoink thin film devices were obtained using a probe station and precision source-measure unit, with and without illumination, under ambient atmosphere and at room temperature. Fig. 1d shows current vs. voltage curves obtained for a typical photodetector device, which display current increasing proportional to incident light intensity. This behavior can be explained by electron-hole pair creation and desorption of surface oxygen species (leading to vacancies that act as donors) upon photon absorption, which leads to an increase in conductance. This is consistent with previous studies where ZnO thin films have been used for photoconductive sensor applications, validating PBM nanoink as a suitable synthesis technique for the active material in photodetectors.Compared to standard ZnO thin films, the PBM nanoink method allows both particle dimensions and surface states to be tailored and optimized for different photodetector applications in a straightforward manner by adjusting grinding conditions. In particular, both UV and visible light detection can be tuned via the solution-based ZnO nanoink approach presented without additional material/chemical processing. Such PBM nanoinks thus offer the potential of realizing low-cost photodetectors and multifunctional thin film coatings for applications in optoelectronics, imaging, environmental monitoring and communications.

Gaomiaozi bentonite colloids: Interactions with plutonium (IV) and zirconium (IV)

According to previous field experiments, carrier colloids represent the primary mechanism for enhancing the transport of actinides in the subsurface at former nuclear weapons facilities. However, sub-micrometer size investigations on the sorption/interactions between radionuclides and natural colloids are scarce. In the present study, interactions between Pu (IV)/Zr (IV) and the colloids formed from Chinese Gaomiaozi bentonite in water were evaluated using sorption experiments, scanning electron microscopy, transmission electron microscopy, dynamic light scattering, X-ray photoelectron spectroscopy, and small-angle X-ray scattering. Stable GMZ bentonite colloids showed zeta potentials of –31.8(0.9) mV at 25–85 ℃. Small-angle X-ray scattering from these colloids showed that the d-space (2.12 nm) of the colloidal particles dispersed in water exceeded that of mineral fragments obtained from the bulk powder (1.45 nm) in air, an indication of swelling. In addition, these colloidal particles (336 nm in size) exhibited higher affinities (Kd ~ 104 mL g−1) for Pu (IV) compared with bulk GMZ fragments (Kd ~ 103 mL g−1) at pH 7. X-ray diffraction showed that montmorillonite was the primarily component of colloidal GMZ particles, while X-ray photoelectron spectroscopy indicated that this clay mineral played an important role in the interaction with Pu (IV)/Zr (IV). Small-angle X-ray scattering from Zr (IV) solutions, showed power-law scattering (Intensity ∝ q−α) exponent α that increased from 2.6 to 3.4 (0.1 nm−1 <q < 0.5 nm−1), and decreased from 1.56 to 0.87 (q ~ 0.2 nm−1) as the Zr (IV) was raised from 0 to 9.8 × 10–11 mol dm–3. These results related to the partial agglomeration and precipitation of GMZ bentonite colloids. The remaining associative colloids pose a potential threat of Pu (IV) or Zr (IV) migration in subsurface waters.

Study on the evaluation and formulation of zolpidem tartrate

Traditional solid dose forms have a number of drawbacks, including difficulties in swallowing as patients get older, a delayed commencement of action, and issues with physiological factors such as the length of time it takes for the stomach to empty. A tablet that dissolves in the mouth is a relatively recent development in the field of drug delivery. The use of zolpidem in the treatment of insomnia for a relatively short period of time is preferred. The purpose of this study is to improve the bioavailability of zolpidem tartrate and get around the effect of the first transit through the body by formulating and evaluating mouth-dissolving tablets of the drug. The tablet containing Zolpidem was made by employing the directed compression method, with croscarmellose sodium and sodium starch glycolate serving as the super disintegrants, and mannitol, microcrystalline cellulose, and dicalcium phosphate serving as the diluents. The effects of several super disintegrants and diluents on disintegration and dissolving time were optimized, and the formula was completed on the basis of these characteristics. The FTIR investigation revealed that the medication and the excipients were compatible with one another. According to the results of the pre-compression investigation, the bulk powder possesses outstanding flow qualities and falls within a range of pharmacopoeia standards that is considered acceptable. The findings of the post-compression evaluation of the parameters match the criterion that was anticipated. From all of the different formulations, the one that had the highest amounts of sodium starch glycolate (35 mg), mannitol (20 mg), and microcrystalline cellulose yielded the greatest results for the In vitro drug release profile (60 mg). These tablets have a hardness that is lower than 4 kg/cm2, a disintegration period that is only 24 seconds long, and they release 97.71 percent of their pharmacological content within 30 minutes.

Effect of Polymer Structure on the Size and Shape of Metal and Metal Oxide Nanopowder: An HR-TEM Approach

A metal and metal oxide quantum dot (QD) was synthesized by a simultaneous oxidative reduction method. Aniline was polymerized both in the presence and absence of o-toluidine (OT) as a co-monomer and in the presence of peroxomonosulfate (PMS) as a free radical initiator in N-methyl pyrrolidone (NMP) medium at 0–5∘C for 3 h under vigorous stirring condition. The metal or metal oxide bulk powder was used as source material for the generation of QD. At the end of the reaction a dark green colored polymer was formed, filtered and dried at 110∘C for overnight. The dried polymer was subjected to HR-TEM analysis. The size and shape of the crystals formed were noted and compared with the literature reports.

Stability evaluation of compounded hydroxyurea 100 mg/mL oral liquids using a novel analytical method involving chemical derivatization.

This study assessed the stability of six extemporaneously compounded hydroxyurea oral liquids stored at room temperature. Hydroxyurea oral liquids (100 mg/mL) were prepared using three different mixing methods (mortar, mixer or QuartetRx) from either bulk powder, capsule content, or whole capsules. Two brands of capsules were tested in this study. All formulations were stored at room temperature (25°C / 60% RH) in amber plastic bottles for 90 days and amber plastic syringes for 14 days. Physical stability was assessed visually, while chemical stability was evaluated using a stability-indicating high-performance liquid chromatography method. Chemical derivatization with xanthydrol allowed the retention of hydroxyurea on a reverse-phase column. At least 93.9% and 97.0% of the initial concentration of hydroxyurea remained after 90 days in bottles and 14 days in syringes, respectively. There were no visual changes in formulations over the study period. Changes in pH up to 1.6 units were observed after 90 days of storage and were explained most likely by an ammonium generating degradation pathway. Ammonium was quantified and remained within safe levels in each HU 100 mg/mL oral preparations. Hydroxyurea oral liquids were all stable for 90 days in amber plastic bottles and 14 days in amber plastic syringes.

Analysis of two mixtures containing racetams in their pharmaceuticals using simple spectrophotometric methodologies

Green spectrophotometric methods were developed and validated for determination of some CNS active drugs as antiepileptics and brain stimulants. Piracetam (PIR), Levetiracetam (LEV) and Brivaracetam (BRV) were assayed as a ternary mixture using double divisor-ratio spectra derivative (DDRSD) (method I). One more binary co-formulated mixture of Piracetam (PIR) and Vincamine (VIN) was assayed using difference spectrophotometric procedures (method II). I was applied to determine PIR at 302nm in the first derivative of the ratio spectra in the selected spectral region. The content of LEV was determined by measuring the spectra at 215nm in the first derivative of the ratio spectra in the selected spectral region. The concentration of BRV was estimated by measuring the first derivative of the ratio spectra in the chosen spectral region and detecting the signals at 229.7nm. The application of method (II) procedures resulted in measuring the absorbance of PIR at 220nm which is the zero crossing point on the difference spectra of VIN in 0.1M NaOH vs. 0.1M HCl. Similarly, the absorbance of VIN was measured at 245.0nm, which is the zero crossing point on the difference spectra of PIR. The suggested methods were fully validated adopting ICH guidelines. The linearity ranged from 10-100μg/mL for the three racetams and from 2-20 for VIN. The recovery percentages were ranged from 98.72% to 101.8% for method I and from 98.13% to 101.06% for method II. Moreover, the proposed methods were proved environmentally benign using the most recent assessment tool named AGREE. Both procedures were successfully applied for the determination of each drug in bulk powder, checked using laboratory prepared mixtures, and directly applied on commercially available pharmaceutical products without interference. The obtained results revealed a good agreement with those obtained by the reported methods.

Elasto-plastic and adhesive contact: An improved linear model and its application

An improved linear model is developed for elasto-plastic and adhesive contact. New correlations are proposed and validated to estimate the key parameters of the model, including contact stiffness, yield point, maximum pull-off force and time step. The newly proposed contact model is applied to the analysis of single particle contact behaviour upon impact and bulk particle flow behaviour by DEM simulations. The results show that both single particle and bulk powder behave more “cohesively” if contact plastic deformation is considered. A cohesion yield number is proposed to describe the extent of yielding when cohesive particles are in contact with each other. There is a critical particle size, below which the effect of plastic deformation becomes prominent and must be considered. This provides a new framework and criteria for elasto-plastic and adhesive contact model, and a step towards understanding the effect of plastic deformation on the behaviour of cohesive particles.

RP-HPLC-UV Method Development and Validation for the Determination of Molnupiravir in Bulk Powder and Pharmaceutical Formulation.

RP-HPLC-UV Method Development and Validation for the Determination of Molnupiravir in Bulk Powder and Pharmaceutical Formulation.

Assessing the Interrelationship of Microstructure, Properties, Drug Release Performance, and Preparation Process for Amorphous Solid Dispersions Via Noninvasive Imaging Analytics and Material Characterization.

The purpose of this work is to evaluate the interrelationship of microstructure, properties, and dissolution performance for amorphous solid dispersions (ASDs) prepared using different methods. ASD of GDC-0810 (50% w/w) with HPMC-AS was prepared using methods of spray drying and co-precipitation via resonant acoustic mixing. Microstructure, particulate and bulk powder properties, and dissolution performance were characterized for GDC-0810 ASDs. In addition to application of typical physical characterization tools, we have applied X-Ray Microscopy (XRM) to assess the contribution of microstructure to the characteristics of ASDs and obtain additional quantification and understanding of the drug product intermediates and tablets. Both methods of spray drying and co-precipitation produced single-phase ASDs. Distinct differences in microstructure, particle size distribution, specific surface area, bulk and tapped density, were observed between GDC-0810 spray dried dispersion (SDD) and co-precipitated amorphous dispersion (cPAD) materials. The cPAD powders prepared by the resonant acoustic mixing process demonstrated superior compactibility compared to the SDD, while the compressibility of the ASDs were comparable. Both SDD powder and tablets showed higher in vitro dissolution than those of cPAD powders. XRM calculated total solid external surface area (SA) normalized by calculated total solid volume (SV) shows a strong correlation with micro dissolution data. Strong interrelationship of microstructure, physical properties, and dissolution performance was observed for GDC-0810 ASDs. XRM image-based analysis is a powerful tool to assess the contribution of microstructure to the characteristics of ASDs and provide mechanistic understanding of the interrelationship.

Implementation of different separation techniques for resolving ternary mixture of Paracetamol, Pseudoephedrine Hydrochloride and Chlorpheniramine maleate with further quantification

Abstract Due to the wide applicability of separation techniques that rely on the property of differential migration in pharmaceutical formulations analysis, different analytical strategies have been proposed to resolve mixtures of multi-components pharmaceuticals. Three separation methods were developed and validated for the simultaneous determination of Paracetamol (PAR), Pseudoephedrine HCl (PSE) and Chlorpheniramine maleate (CHP). The first method is a thin-layer chromatographic (TLC) separation, followed by densitometric measurement. The separation was carried out on aluminium sheet of silica gel 60 F254 using ethanol:chloroform:ammonia (1:7:0.4, by volume) as the mobile phase. Determination of PAR, PSE and CHP was successfully applied over the concentration ranges of 3–25 µg/band, 0.5–10 µg/band and 0.1–6 µg/band, respectively. The second method is HPLC separation that was achieved on C18 column using the mobile phase acetonitrile:phosphate buffer pH 5 (10:90, v/v) at a flow rate 1 mL min−1. PAR, PSE and CHP were determined by HPLC in concentration ranges of 5–400 μg mL−1, 2–40 μg mL−1 and 0.5–16 μg mL−1, respectively. The third method is a capillary electrophoresis (CE) separation. The electrophoretic separation was achieved using 20 mM phosphate buffer (pH 6.5) at 20 kV. The linearity was reached over concentration ranges of 30–250 μg mL−1, 5–50 μg mL−1 and 0.8–20 μg mL−1 for PAR, PSE and CHP, respectively. The developed methods were validated with respect to linearity, precision, accuracy and system suitability. The proposed methods were successfully applied for bulk powder and dosage form analysis with RSD of precision &lt;2%. Moreover, statistical comparison with the official methods confirms the methods' validity.

Rapid-field-deployable DART-MS screening technique for 87 opioids and drugs of abuse, including fentanyl and fentanyl analogs

Fentanyl and fentanyl analogs are playing an increasing role in the opioid health crisis that is sweeping America. These synthetic opioids are much more potent and lethal than morphine or heroin and must be treated with extreme caution. Many of these substances are entering the country through International Mail Facilities (IMFs) and Express Courier Hubs (ECHs) in the form of counterfeit prescription drugs and bulk powders, resulting in a critical need for field-deployable techniques that can safely provide rapid screening to prevent these products from reaching the public. Here we describe a direct analysis in real time thermal desorption mass spectrometer (DART-MS) with database searching capabilities that allows quick detection of numerous target compounds. Minimum detectable levels for 87 opioids and drugs of abuse have been determined. This technique was applied to eight samples sent to the Food and Drug Administration’s (FDA) Forensic Chemistry Center for analysis and the results are compared to those collected using gas chromatography with mass spectral detection (GC-MS) and liquid chromatography with mass spectral detection (LC-MS).