Solid oral dosage form manufacturing using injection moulding

The most preferred route of drug administration is via an oral dosage form and currently the most widely used manufacturing method is direct compression of powder blends. However it can be difficult to control the homogeneity of these dosage forms due to inefficient mixing. Dispersing API within a molten polymer can give more control over the spatial arrangement of drug within the dosage forms resulting in higher quality doses. Using polymers also has the added benefit that drug-polymer interactions can increase solubility of drugs reducing the growing concern of the number of aqueous insoluble drugs on the market (1). Injection Moulding (IM) is a novel method to produce dosage forms. It works by melting formulations containing polymer and drug together and injecting it into a cavity. By combining this technology with Hot Melt Extrusion (HME) which introduces highly efficient mixing the drug dose can be controlled. However the main disadvantage to using polymers is that sustained release often occurs due to the slow erosion properties and high pressures used during injection moulding(2). Stability issues can also occur when using high drug loadings as the polymer becomes saturated. Disintegrating agents can be introduced to the formulation in order to increase the time taken to obtain complete drug release. It is important to note that due to the nature or polymer true ‘disintegration’ won’t occur as it does with compressed tablets however they do have the ability to help facilitate the breakdown of polymers(3) . Filaments were produced using HME based on a Design of Experiments approach were analysed using disintegration apparatus and the results suggests the best disintegrating agents to use were small natural molecules. However the main factor influencing the mass remaining was the concentration of API as this was a BCS Class II drug. References 1. Karataş A, Yüksel N, Baykara T. 'Improved solubility and dissolution rate of piroxicam using gelucire 44/14 and labrasol'. Il Farmaco. 2005;60(9):777-82. 2. Claeys B, Vervaeck A, Hillewaere XKD, Possemiers S, Hansen L, De Beer T, et al. 'Thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding'. E. J. Pharm. Biopharm. 2015;90:44-52. 3. Agrawal A, Dudhedia M, Deng W, Shepard K, Zhong L, Povilaitis E, et al. 'Development of tablet formulation of amorphous solid dispersions prepared by hot melt extrusion using quality by design approach'. AAPS PharmSciTech. 2016;17(1):214-32

Injection moulding : a novel approach to the manufacture of homogenous immediate release solid oral dosage forms

The current methods of dosage form production do not control the API spatial arrangement especially when using powder blends. This research aims to use Injection Moulding as a novel alternative method taking advantage of the benefits of drug-polymer interactions. Initial studies of paracetamol PVP formulations provided units that contained crystalline paracetamol due to inefficient mixing. Methods to produce solid dispersions prior to injecting such as Hot Melt Extrusions may be necessary

Novel heuristic for low-batch manufacturing process scheduling optimisation with reference to process engineering

YesScheduling is an important element that has a major impact on the efficiency of all manufacturing processes. It plays an important role in optimising the manufacturing times and costs resulting in energy efficient processes. It has been estimated that more than 75% of manufacturing processes occur in small batches. In such environments, processes must be able to perform a variety of operations on a mix of different batches. Batch-job scheduling optimisation is the response to such low batch manufacturing problems. The optimisation of batch-job process scheduling problem is still a challenge to researchers and is far from being completely solved due to its combinatorial nature. In this paper, a novel hybrid heuristic (HybH) solution approach for batch-job scheduling problem is presented with the objective of optimising the overall Makespan (Cmax). The proposed HybH is the combination of Index Based Heuristic (IBH) and the Finished Batch-Job (FBJ) process schedule. The heuristic assigns the first operation to a batch-job using IBH and the remaining operations on the basis FBJ process schedule. The FBJ process schedule gives priority to the batch-job with early finished operations, without violating the constraints of process order. The proposed HybH is explained with the help of a detailed example. Several benchmark problems are solved from the literature to check the validity and effectiveness of the proposed heuristic. The presented HybH has achieved batch-job process schedules which have outperformed the traditional heuristics. The results are encouraging and show that the proposed heuristic is a valid methodology for batch process scheduling optimisation

Measured Water Temperature Characteristics in a Pipeline Distribution System

YesThis paper describes the design, development, deployment and performance assessment of a prototype system for monitoring the 'health' of a water distribution network based on the temperature distribution and time-dependent variations in temperature across the network. It has been found that the water temperature can reveal unusual events in a water distribution network, indicated by dynamic variations in spatial temperature differential. Based on this indication it is shown how patterns of changes in the water temperature can be analysed using AQUIS pipeline distribution software and used in conjunction with hydraulic (e.g. flow and pressure) sensors to indicate the state of ¿health¿ of the network during operation

A new paradigm for disc-pad interface models in friction brake system

In this paper a 2D coupled thermal-stress finite element model is established and used to predict thermal phenomena at the disc-pad interface of a disc brake system. The importance of certain critical settings and parameters for the 2D FE model has been identified (such as, a limited degree of freedom for a brake pad in place of accepted practice that considers uniform contact), here a non-uniform pressure distribution resulting from friction bending moment effects due to the introduction of a pivot point. These parameters affect the distributions of both interface temperature and pressure. The simulation results show that when the interface conductance h is 10^6 W/m^2K or higher, the interface temperature distribution is no longer sensitive to friction bending moment effects. However, when h is 30000 W/m^2K or lower, the interface temperature distribution and heat partition ratio are significantly affected by the setting used for the rotational degree of freedom of the pad. The simulation results provide a useful reference for a better design of a disc brake system for different applications

Artificial Neural Network Model for a Low Cost Failure Sensor: Performance Assessment in Pipeline Distribution

YesThis paper describes an automated event detection and location system for water distribution pipelines which is based upon low-cost sensor technology and signature analysis by an Artificial Neural Network (ANN). The development of a low cost failure sensor which measures the opacity or cloudiness of the local water flow has been designed, developed and validated, and an ANN based system is then described which uses time series data produced by sensors to construct an empirical model for time series prediction and classification of events. These two components have been installed, tested and verified in an experimental site in a UK water distribution system. Verification of the system has been achieved from a series of simulated burst trials which have provided real data sets. It is concluded that the system has potential in water distribution network management

A finite element model of the electrofusion welding of thermoplastic pipes

An advanced finite element (FE) model of the electrofusion welding of thermoplastic pipes has been developed using the ABAQUS FE package. The heat transfer analysis is coupled with thermal deformation analysis to include the time-dependent closure of the initial gap between the pipe and fitting. The effect of radial melt movement into the interface is modelled using a new `virtual material movement¿ technique. The predicted results (temperature distribution in the weld region, melt affected zones and gap closure time) are compared with experimental data and good agreement is foun

Regulating Medicines in a Globalized World With Increased Recognition and Reliance Among Regulators: A National Academies Report

Research and development of pharmaceuticals are now complex global endeavors, with drug companies operating worldwide using global supply chains. Pharmaceutical companies source their products from many countries, conduct trials in multiple sites, and market essential drugs and vaccines globally. Yet oversight of drug safety and effectiveness is primarily the responsibility of national regulators of variable capacities. National agencies often undertake product reviews without recognizing that similar reviews are occurring elsewhere, sometimes simultaneously. The result is duplication and redundancy, which benefits neither national nor global public health. Supported by the US Food and Drug Administration (FDA), the National Academies of Sciences, Engineering, and Medicine convened an expert committee to explore the benefits of mutual recognition and other reliance activities among regulators. Even well-resourced regulators (for example, the FDA, the European Medicines Agency, the Pharmaceutical and Medical Devices Agency Japan, and Health Canada) find it difficult to ensure the safety, efficacy, and quality of medicines in a globalized world. Regulatory failures cause harm to the population and undermine public trust in government. In 2008, following discovery of contaminated heparin originating from China, the Bush administration authorized the FDA to coordinate certain product manufacturing inspections with Australian and European regulators in China and India—setting the stage for “third country” inspections (ie, inspections conducted outside the jurisdiction of either regulator). Yet concerns about the quality of active pharmaceutical ingredients and finished pharmaceutical products persist. For example, in 2018, the FDA recalled generic medications used to treat hypertension and cardiovascular disease because of contamination

Bi-fuel SI Engine Model for Analysis and Optimization

YesThe natural gas as an alternative fuel has economical and environmental benefits. Bi-fuel engines powered by gasoline and compressed natural gas (CNG) are an intermediate and alternative step to dedicated CNG engines. The conversion to bi-fuel CNG engine could be a short-term solution to air pollution problem in many developing countries. In this paper a mathematical model of a bi-fuel four-stroke spark ignition (SI) engine is presented for comparative studies and analysis. It is based on the two-zone combustion model, and it has the ability to simulate turbulent combustion. The model is capable of predicting the cylinder temperature and pressure, heat transfer, brake work , brake thermal and volumetric efficiency, brake torque, brake specific fuel consumption (BSFC), brake mean effective pressure (BMEP), concentration of CO2, brake specific CO (BSCO) and brake specific NOx (BSNOx). The effect of engine speed, equivalence ratio and performance parameters using gasoline and CNG fuels are analysed. The model has been validated by experimental data using the results obtained from a bi-fuel engine. The results show the capability of the model in terms of engine performance optimization and minimization of the emissions. The engine used in this study is a typical example of a modified bi-fuel engine conversion, which could benefit the researchers in the field