Poeiervermenging : 'n ondersoek na die vermenging van mikrokonsentrasiemengsels

Abstract

The general theory of mixing and the factors which affect the process were discussed. The mixture quality and the rate of mixing must be evaluated during the mixing process. The theoretical models which may be used to describe the quality and the mixing rate were reviewed. The necessity to differentiate between micro concentration mixtures and mixtures with more favourable mixing ratios of the components was discussed. In some cases of micro concentration mixing interaction between the components exists. These interactions alter the characteristics of the mixing process. The mixing of powders is an importand process in the pharmaceutical industry and it is related to the content uniformity as well as the physical properties of the dosage forms which are manufactured from powder mixtures. The characteristics properties of powders must be borne in mind when existing mixing theories are applied to micro concentration mixing. The general properties of powders for example the flow properties and cohesion

were discussed. The application of the quality model for predicting the final state of a micro concentration mixture was outlined. The unique properties o f powders complicate the application of the quality mode ls to micro concentration mixing . It is difficult to estimate the number of particles in a sample and the powder properties which affect this estimation were pointed out. The important factors in the experimental determination of the mixing quality of powder mixtures for example the volume and the mass of the samples , the number of samples and the importance of the analytical method were discussed . A complicating factor is encountered in the fact that the state of an intermediately mixed mixture cannot be completely characterised by the variance between a number of samples. The general quality model of Kristensen was discussed. According to this model it is obvious that knowledge of the structure of the mixture is a necessary requirement for assessing the quality of a mixture. The problems encountered when the Kristensen model is applied to a micro concentration mixture were discussed.

Chapter 3. The mixing of reserpine (micro component) and lactose (carrier) was done in a small cylindrical tumbling mixer . A small mixer was chosen because it is easier to control the properties of the components and the whole mixture could be analysed without increasing the number of samples to the extent that it would be impossible to analyse all the samples. The mixers , the preparation of the components and the sampling techniques were discussed. The properties of the components f or example the particle size, shape and flow properties were determined . The reserpine concentration in t he samples was deteremined by a spectro-photometrical method. The precision and the variance of the analytical method was estimated. Chapter 4. The mixing of 0,1% reserpine, with a mean particle size of 7 ,62 μm, and lactose (356 ,5 μm) was carried out in a small cylindrical tumbling mixer to investigate the postulated mixing mechanism and the structure of the mixture. After 30 seconds of mixing the structure of the mixture could be expressed in terms of two characterising properties i.e. the mean size of the absorbed reserpine agglomerates and the adsorbed

fraction. After 600 seconds all the reserpine was adsorbed on the lactose and the rate determining step was the attrition of the adsorbed agglomerates. The mixing rate, expressed in terms of the mean size of adsorbed agglomerates and the adsorbed fraction , as a function of the properties of components was investigated. Lactose with mean particle sizes of 249 , 9 201,5 and 194 , 9 μm was mixed with reserpine (7 , 62μm). It was found that the disintegration of the reserpine agglomerates and the attrition of the adsorbed agglomerates was rate determining . The mixing rate, using the three different particle sizes of the lactose, was therefore determined by the properties of the reserpine. Mixtures (0,1% and 1,0% reserpine) were made by triturating lactose and reserpine in an agate mortar. The results supported the existance of agglomerates in the mixtures that were made in the tumbling mixer. After 1 200 seconds the mixture qualities in the cylindrical mixer were the same as the quality of the complete randomised state for mixtures of 0,1% reserpine (7,62 μm) and lactose (356,5 μm). Better qualities could have been obtained but it could not be proved as a result of the variance of the analytical method. One of the mixtures was subjected to a segregation test in a fluid-bed. Samples withdrawn after the test had a content of+ 75%of the original between the reserpine and the lactose particles.