Product optimisation studies

At the early stages of optimisation, preformulation studies are usually conducted to screen excipients or packaging materials and to select those compatible with the candidate drug, using accelerated stress testing procedures. More details about the preformulation techniques, which can be employed for compatibility studies, are discussed in Chapter 3. The importance of doing compatibility studies is for reducing the number of excipients and formulation options to test in further product optimisation studies. 

The exact product optimisation studies to be conducted will depend on the type of ophthalmic dosage form to be developed (liquid drops, semi-solid gel/ointment or solid device). However, the dosage form type should be clearly defined from the product design evaluation and supporting preformulation studies, to enable the formulator to focus on the most relevant product optimisation studies. 

Optimisation studies were carried out to establish the optimum outlet temperoture of the process stream from the Production Coolers. 

Tober A J, Sanders, T G - Glycol System and Production Cooler Optimisation Study for the North Rankin A Platform, Worley Engineering Report No 25, December 1979. 

Using the model, Barolo et al. (1998) further studied the dynamic behaviour of the column and interactions of different design and operating parameters on the column operability and productivity were established. See the original reference for further details. The optimisation study carried out by Greaves et al (2003) using a Neural Network based dynamic model is presented in Chapter 12. 

Greaves et al. (2003) proposed a framework to optimise the operation of MVC columns with substantial reduction of the computational power needed to carry out the optimisation calculations. The framework relies on the use of NN based process model. The optimisation of a pilot-plant middle-vessel batch column (MVC) was considered to test the viability of the proposed framework. The maximum product problem was considered and solved by optimising the column operating parameters, such as the reflux and reboil ratios and the batch time. The NN based model is found to be capable of reproducing the actual plant dynamics with good accuracy, and that the proposed framework allows a large number of optimisation studies to be carried out with little computational effort. 

Biphasic solvent mixtures can also be used for chiral cyanohydrin formation. Loos et al. reported optimisation studies during the development of an industrial process for the production of (J )-mandelonitrile [167,168]. A number of crucial reaction parameters such as pH-value, temperature, type of solvent and the phase ratio (organic/aqueous) were varied and optimised to give a highly productive method. 

At the completion of product optimisation, when the best product variant has been selected, it is a good idea to summarise the work conducted in a Product Optimisation Report. The report should reference the primary data from preformulation, product optimisation and stability studies, cross-referencing other investigational reports where necessary. It should clearly justify the recommendations for the quantitative formula and the excipient, component and product specifications. Such a document can be very useful to aid smooth technology transfer into production and for writing regulatory submissions. 

In designing an alloy, polymer chemists choose candidate resins according to the properties, cost, and/or processing characteristics required in the end product. Next, compatibility of the constituents is studied, tested, and either optimised or accommodated. 

Typically, an acetanilide (1 mol. equiv.) was treated with the Vilsmeier reagent generated from POCI3 (7 mol. equiv.) and V,V-dimethylformamide (DMF, 2.5 mol. equiv.) at 75 °C for 4 - 20 h. The reaction products were readily obtained by filtration after pouring the reaction mixture onto ice-water minor reaction products were isolated after basification of the filtrate. A variety of acetanilides were studied under these optimised reaction conditions and some significant observations were noted. Activated acetanilides 3 [e.g. R = 4-Me (70%), 4-OMe (56%)] reacted faster and in better yield to give quinolines 4 than other strongly deactivated systems 3 [e.g. R = 4-Br (23%), 4-Cl (2%), 4-NO2 (0%)] — in these cases, formamidines 5 and acrylamides 6 were the major reaction products. 

The pharmacological activity of the 1,5-benzothiazepine derivative diltiazem has given further impetus for synthetic routes to this ring system. A traditional preparation of the intermediate 62 by the reaction sequence shown in Scheme 12 has been subject to microwave studies, when the final product was obtained as a mixture of isomers <96TL6413>. Under optimised conditions irradiation in toluene at 390 watts for 20 minutes gave mainly the cis-isomer as the main product (cis/trans 9 1) in 75% yield. However, reaction at 490 watts in the presence of acetic acid resulted in a reversal of this ratio and a yield of 84%. The... 

Natural ingredients based lipstick formulations have been prepared. The effects of the natural waxes, oils and solvent compositions on the viscosity and melting point of the lipstick have been studied. The result indicates that the viscosity and melting point of the lipstick can be manipulated by changing the composition of natural candelilla wax, camauba wax and beeswax in the formulation. Another important lipstick characteristic, which is hardness, will be studied. Consumer acceptance towards the product will be investigated. Finally, by relating the consumer data and instrumentation analysis, optimisation process will be conducted. 

Using experimental design such as Surface Response Method optimises the product formulation. This method is more satisfactory and effective than other methods such as classical one-at-a-time or mathematical methods because it can study many variables simultaneously with a low number of observations, saving time and costs [6]. Hence in this research, statistical experimental design or mixture design is used in this work in order to optimise the MUF resin formulation. 

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