Estimation of Drug Particle Size in Intact Tablets by 2-Dimensional X-Ray Diffractometry
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Continuous manufacturing (CM) has been used to produce several immediate release drug products. No extended-release (ER) product manufactured employing CM technology has been approved yet. Herein this study investigated the critical aspects of switching from the batch mode of high shear granulation to the continuous operation of twin-screw granulation for extended-release tablets. Metoprolol succinate ER tablets was used as a model ER formulation for this purpose. A central composite design (CCD) was employed to determine the effects of high shear granulator (HSG) parameters, namely impeller speed, granulation time, and binder liquid feeding rate, on the critical granulation characteristics important for product performance. These critical granulation characteristics served as a guide for switching from the batch processing to the continuous operation for achieving the same breaking strength and dissolution for this ER metoprolol tablets. The granulation time was the most critical factor affecting the bulk properties of granules which contributed to tablet dissolution. The higher density and lower compressibility of granules were attained at the longest granulation time of 5.4 min with the fastest liquid feeding rate of 75 g/min. The granules’ density was the primary factor negatively affecting the dissolution of metoprolol tablets. However, the breaking strength of tablets confounded the effect of granules density on metoprolol dissolution. Switching the processing parameters of high shear granulation to twin-screw granulation achieved similar dissolution profiles (F2 greater than 50). The screw speed was not found to affect bulk properties of granules. The root cause of granulation failures in twin-screw granulation, such as premature consolidation, excessive swelling, poor cohesion, inconsistent shearing effects, and formation of deformed agglomerates, were identified. In conclusion, the use of critical granulation characteristics through a performance-based approach of ER tablets facilitated the switching of manufacturing of an ER formulation form batch to continuous operation.
The pharmaceutical drug product development process can be greatly accelerated through the use of modeling and simulation techniques to predict the manufacturability and performance of a given formulation. The anticipation and possible mitigation of tablet damage due to manufacturing stresses represents a specific area of interest in the pharmaceutical industry for predicting formulation and tableting performance. While the finite element method (FEM) has been extensively used for predicting the mechanical behavior of powder material in the compaction processes, a shortcoming of the approach is the inherent difficulty to predict discontinuities (e.g., damage or cracking) within a tablet as FEM is a continuum-based approach. In this work, we propose a novel method utilizing peridynamics (PD), a numerical method that can capture discontinuities such as tablet fracture, to predict the evolution of damage and breakage in pharmaceutical tablets. The approach links (1) the finite element method – to elucidate the behavior of powders during die compaction – with (2) the peridynamics modeling technique – to model the discontinuous nature of damage and predict tablet breakage during the critical stages of unloading and ejection from the compression die. This short communication presents a proof of concept including a workflow to calibrate the linked FEM-PD simulation models. Further, it demonstrates promising results from a preliminary experimental validation of the approach. Following further development, this approach could be used to guide the optimization of compression processes through targeted changes to formulation material properties, compression process conditions, and/or tooling geometries to deliver improved process efficiency and tablet robustness.
Highlights: • Montmorillonite (MMT) can be intercalated with polyaniline (PANI) chains. • Tablets pressed from PANI/MMT exhibit high anisotropy in electrical conductivity. • Pressure 28MPa is sufficient to reach the anisotropy. • Tablets pressed from pure PANI also exhibit anisotropy in electrical conductivity. - Abstract: Polyaniline-montmorillonite nanocomposite was prepared from anilinium sulfate (precursor) and ammonium peroxodisulfate (oxidizing agent) using simple one-step method. The resulting nanocomposite obtained in powder form has been pressed into tablets using various compression pressures (28–400 MPa). Electrical conductivities of tablets in two perpendicular directions, i.e. direction parallel with the main surface of tablet (σ=) and in orthogonal direction (σ⊥), and corresponding anisotropy factors (i.e., the ratio σ=/σ⊥) have been studied in dependence on compression pressure used during the preparation. Polyaniline-montmorillonite nanocomposite was characterized using X-ray diffraction analysis, raman spectroscopy, transmission electron microscopy, thermogravimetric analysis and molecular modeling which led to the understanding of the internal structure. Measurement of hardness performed on pressed tablets has been also involved. Taking into account the highest value of anisotropy factor reached (σ=/σ⊥ = 490), present study shows a chance to design conductors with nearly two-dimensional conductivity.
This study aimed at understanding the effect of screw design on the critical characteristics of granules and tablets of an extended-release (ER) formulation for twin screw granulation process. The screw design parameters assessed included number of kneading elements (KEs) per kneading zone, distance separating kneading zones, staggering angle (SA) of kneading elements and number of sizing elements (SEs). These input variables were varied using a design of experiment (DoE) approach to manufacture granules. Particle size distribution (PSD), flow and bulk properties of the granules, breaking strength and dissolution of tablets manufactured using these granules were characterized. The results of least square fitting showed that KEs, SA, and SEs of the screws significantly (p -values < 0.05) affected the PSD, cohesion, compressibility (CPS), conditioned bulk density (CBD) and permeability of the granules. The KEs and SEs significantly (p -value < 0.05) affected the dissolution, which was attributed to their effects on CPS and CBD of the granules. The distance between kneading zones had no significant effect on granules and tablet characteristics. Finally, these results may be used to further study the interaction of the identified critical screw design parameters with other processing parameters for continuous manufacturing of this ER matrix-based tablet formulation.
To explore the feasibility of small-scale sintering pot testing, a ‘millipot’ facility (diameter of 53 mm and height of 400 mm) was established and used to examine the sintering performance of iron ores and other non-traditional ferrous materials. The sintering performance of a millipot was examined across a range of different operational conditions (coke rate and suction pressure) and compared with an industrial sinter strand operation. Tablet tests were also performed to assist in the design of the millipot experiments and identify conditions for achieving mineral composition similar to the industrial sinter. For the millipot experiments, the materials used need to be compacted to increase the bulk density, and a higher coke rate is required to compensate the high heat loss caused by wall effects. A higher suction pressure is also necessary to maintain an oxidizing atmosphere in the sinter bed. As expected, it was not possible to eliminate the wall effect, which resulted in more primary hematite at edges of the sintered column. However, the sintered material from the center of column simulates industrial sinter reasonably well. As such, millipot provides a practical way to evaluate the sintering process and material performance at laboratory scale, helping to bridge the gap between tablet sintering and large scale pot sintering, or full scale plant trial. The results of millipot testing can be used for designing larger scale experiments or commercial sintering trials.
Nacre, the iridescent outer lining of pearls and inner lining of many mollusk shells, is made of periodic, parallel, organic sheets alternating with aragonite (CaCO 3 ) tablet layers. Nacre tablet thickness (TT) generates both nacre's iridescence and its remarkable resistance to fracture. Despite extensive studies on how nacre forms, the mechanisms controlling TT remain unknown, even though they determine the most conspicuous of nacre's characteristics, visible even to the naked eye.Thermodynamics predicts that temperature (T) will affect both physical and chemical components of biomineralized skeletons. The chemical composition of biominerals is well-established to record environmental parameters, and has therefore been extensively used in paleoclimate studies. The physical structure, however, has been hypothesized but never directly demonstrated to depend on the environment. Here we observe that the physical TT in nacre from modern and fossil shallow-water shells of the bivalves Pinna and Atrina correlates with T as measured by the carbonate clumped isotope thermometer. Based on the observed TT vs. T correlation, we anticipate that TT will be used as a paleothermometer, useful to estimate paleotemperature in shallow-water paleoenvironments. Here we successfully test the proposed new nacre TT thermometer on two Jurassic Pinna shells. The increase of TT with T is consistent with greater aragonite growth rate at higher T, and with greater metabolic rate at higher T. Thus, it reveals a complex, T-dependent biophysical mechanism for nacre formation.
Oral mucositis is a common unpreventable complication associated with chemoradiation therapy. Shuanghua Baihe tablets have been approved by the Chinese Food and Drug Administration for treating recurrent oral mucosa ulceration. This study assessed whether Shuanghua Baihe tablets could prevent oral mucositis during chemoradiation therapy for locally advanced nasopharyngeal carcinoma.
'simuwatt Energy Auditor' (TM) is a new tablet-based electronic auditing tool that is designed to dramatically reduce the time and cost to perform investment-grade audits and improve quality and consistency. The tool uses the U.S. Department of Energy's OpenStudio modeling platform and integrated Building Component Library to automate modeling and analysis. simuwatt's software-guided workflow helps users gather required data, and provides the data in a standard electronic format that is automatically converted to a baseline OpenStudio model for energy analysis. The baseline energy model is calibrated against actual monthly energy use to ASHRAE Standard 14 guidelines. Energy conservation measures from the Building Component Library are then evaluated using OpenStudio's parametric analysis capability. Automated reporting creates audit documents that describe recommended packages of energy conservation measures. The development of this tool was partially funded by the U.S. Department of Defense's Environmental Security Technology Certification Program. As part of this program, the tool is being tested at 13 buildings on 5 Department of Defense sites across the United States. Results of the first simuwatt audit tool demonstration are presented in this paper.
• To provide an overview of the MC Tablet Hybrid software. • To communicate changes in Work Order (WO) generation and distribution. • Provide step by step process for electronic WO data entry for sampler inspection forms.
• To provide an overview of the MC Tablet Hybrid software. • To communicate the new procedure EP-DIV-SOP-20224. • To communicate changes in Work Order (WO) generation and distribution. • To provide step-by-step process for electronic WO data entry for control measure inspection forms.
A facility is connected to an electricity utility and is responsive to Demand Response Events. A plurality of devices is each individually connected to the electricity grid via an addressable switch connected to a secure network that is enabled to be individually switched off by a server. An occupant of a room in control of the plurality of devices provides via a Human Machine Interface on a tablet a preferred order of switching off the plurality of devices in case of a Demand Response Event. A configuration file based at least partially on the preferred order and on a severity of the Demand Response Events determines which devices which of the plurality devices will be switched off. The server accesses the configuration file and switches off the devices included in the configuration file.
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The Retrocommissioning Sensor Suitcase is targeted for use in small commercial buildings of less than 50,000 square feet of floor space that regularly receive basic services such as maintenance and repair, but don't have in-house energy management staff or buildings experts. The Suitcase is designed to be easy-to-use by building maintenance staff, or other professionals such as telecom and alarm technicians. The software in the hand-held is designed to guide the staff to input the building and system information, deploy the sensors in proper location, configure the sensor hardware, and start the data collection.
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