Process development design matrix

Following an experimental design approach for developing a matrix of variables is undoubtedly a preferable method for conducting experimental studies. This type of an approach to process validation may be suitable for experimental design, but becomes extremely cumbersome when reproducibility of the process and consistent product quality is to be demonstrated. In the absence of the many studies required to fulfill a complex matrix, a simpler matrix based on the edges of a defined range would be reasonable and scientifically valid. 

Once the process or design variables have been identified, a statistically designed experiment should be employed to collect appropriate data to fit the model. This plan includes developing the experimental objective, design matrix, and sample size (i.e., number of experimental replicates). 

In several investigations the feasibility of development of a sustained-release form for diclofenac sodium was studied. Matrix-type formulation was designed, which appears to be a very attractive approach from process development and scale up points of view. HPMC is the most important hydrophilic polymer used for the preparation of oral controlled-release drug-delivery systems. - One of the most important characteristics of HPMC is the high swellability, which has a considerable effect on the release kinetics of the incorporated drug. 

For most composite materials and processes, design must incorporate some material and processing effects knowledge. Sheet forming adds complexity because the process moves fibres and matrix from one conformation to another dynamically. Figure 5.2 shows one possible design process that requires iterative numerical design and process development. 

Poly(phenylene sulfide) (PPS) is another semicrystalline polymer used in the composites industry. PPS-based composites are generally processed at 330°C and subsequently cooled rapidly in order to avoid excessive crystallisation and reduced toughness. The superior fire-retardant characteristics of PPS-based composites result in appHcations where fire resistance is an important design consideration. Laminated composites based on this material have shown poor resistance to transverse impact as a result of the poor adhesion of the fibers to the semicrystalline matrix. A PPS material more recently developed by Phillips Petroleum, AVTEL, has improved fiber—matrix interfacial properties, and promises, therefore, an enhanced resistance to transverse impact (see PoLYAffiRS containing sulfur). 

The method of approach given here works best if a diagram of the process model is first produced, such as shown in Figure 1. To simplify matrix development and look at the problem as a process design, do not think of the matrix in terms of equations. Rather, the rows are... 

The development of on-line sensors is a very costly and time-consuming process. Therefore, if one has available a dynamic model of the reactor which predicts the various polymer (or latex) properties of interest, then this can be used to guide one in the selection and development of sensors. Ideas from the optimal statistical design of experiments together with the present model expressed in the form of a Kalman filter have been successfully used (58) to select those combinations of existing or hypothetical sensors which would maximize the information that could be obtained on the states of the polymerization system. Both the type of sensors and the precisions necessary for them are easily investigated in this way. By changing the choice of the measurement matrix and... 

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