No description available.

Polymorphism and crystallinity are now recognised as important issues in drug development. This is shown by the increased amount of research in this area over recent years. In pharmaceutical development milling is an important unit operation for size reduction to improve powder handling, processing and dissolution rate. The aim of this thesis was to investigate the effect of ball milling (and cryo-milling) on the solid state properties, including amorphous drug formation, of pharmaceutical solids. Milling was carried out using an oscillatory ball mill (Mixer Mill MM301, Retsch GmbH & Co., Germany). In cryo-milling the milling jars were immersed in liquid nitrogen for three min before milling. XRPD was used as the main technique to evaluate the milled samples. Ranitidine hydrochloride (RAN) and indomethacin (INDO) were the model drugs used in this study. It was found that upon milling, RAN form 1 converts to RAN form 2 via an amorphous phase. A faster amorphization rate was observed when the crystalline samples were cryo-milled. Amorphous ranitidine hydrochloride was characterized to have a glass transition (T[g]) range of 13 to 30 �C and a crystallization exotherm (T[c]) between 30 and 65 �C. Conversion was found to occur faster when the temperature of the solid powder was greater than the T[c]. Under various storage conditions, similarly, crystallization of the amorphous phase mainly led to RAN form 2. However, some form 1 and amorphous phase was also detected on the XRPD diffractograms. Using partial least squares regression, the amount of solid form components in the ternary RAN mixtures were successfully quantified. RAN form 2 did not convert to form 1 under any milling (including cryo-milling) or storage conditions used in this study. Overall, RAN form 2 was found to be the thermodynamically stable form and the two (RAN) polymorphs are likely to be a monotropic pair. In a co-milling study of INDO and RAN, the two crystalline drugs were successfully converted into a single amorphous phase after 60 min of co-milling in a cold room (4 �C). The T[g] range (26-44 �C) was also characterized for these mixtures. DRIFTS spectra of the co-milled amorphous samples indicated an interaction had occurred between the carboxylic acid carbonyl (HO-C=O) and benzonyl amide (NC=O) of the INDO molecule with the aci-nitro (C=NO₂) of RAN. Depending on the ratio of INDO to RAN, in general, the amorphous mixtures were stable at 4 �C after 30 days of storage. Crystallization was faster when the binary mixtures were stored at higher temperature or contained higher amounts of RAN in the mixture. Although XRPD and DRIFTS suggested an interaction between the two drugs, co-crystal formation was not observed between INDO and RAN. Ball milling can be used to produce amorphous drug. The rate and extent of amorphization is dependent on the milling conditions. A faster rate of amorphization was observed when the crystalline drugs were cryo-milled. Amorphous drug formation can be made either alone or in combination with another crystalline drug. Amorphization could offer a significant improvement on the dissolution profile and the bioavailability of the poorly water soluble drug - indomethacin. Furthermore, ball milling can also be used to produce a homogenous mix between solids. The �goodmix� effect can be used for seed-induced crystallization or, when the XRPD or Raman data were combined with partial least squares regression, to create a reliable calibration model for quantitative analysis.

No description available.

Os moinhos de bolas são equipamentos presentes em plantas de mineração, sendo uma máquina importante no circuito de cominuição de minérios. Em função de inúmeros fatores como, por exemplo, projeto, fabricação, sobrecarga no equipamento, falta de manutenção e procedimentos de operação inadequados, são desenvolvidas descontinuidades nos componentes estruturais desse equipamento. Os componentes estruturais dos moinhos, basicamente, corpo, tampas e munhões, além do custo elevado, possuem prazos de fabricação que podem variar de dois a três anos dependendo da demanda do mercado. Portanto é cada vez mais necessário que as descontinuidades detectadas nesses componentes sejam corretamente avaliadas. Neste trabalho analisaram-se pela mecânica da fratura a criticalidade de descontinuidades, tais como trincas constatadas em um munhão de um moinho de bolas e compararam-se os valores teóricos de taxa de propagação (crescimento) dessas descontinuidades com valores reais obtidos por meio de inspeções periódicas realizadas neste componente. A nucleação das trincas foi causada por falta de lubrificação nos mancais do moinho, gerando esforços térmicos circunferenciais no munhão, em que a temperatura estimada do contato munhão e bucha atingiu a faixa de 100 °C a 150 °C. No período analisado, os resultados obtidos por meio da norma BS7910 mostraram-se mais próximos dos valores reais do que a norma ASME Seção XI, Apêndice A. O tamanho da trinca mais crítica foi aceito pelos critérios da norma BS7910 e aprovado apenas na condição de emergência da norma ASME Seção XI, Apêndice A. / The grinding ball mills are equipments present in mining plants, being important in the ore comminution circuits. Depending on numerous factors, such as, for example, design, manufacturing, overloads, poor maintenance and inadequate operating procedures, flaws are developed in the structural components of this equipment. The structural components of a mill, basically, shell, heads and trunnions, besides high costs, have lead times that might vary from two to three years, according to market demand. Therefore, it becomes increasingly necessary that any flaws in those components to be properly evaluated. This paper analyzed the fracture mechanics of the criticality of flaws, such as cracks observed in a ball mill trunnion and compared the theoretical values of growth rate of these defects with actual values obtained through periodic inspections performed in this component. The cracks nucleation was caused by lack of lubrication in the trunnion bearings, generating circumferential thermal stresses, thus the estimated temperature of the trunnion and bushing contact achieved the range 100 °C to 150 °C. During the analyzed period, the results obtained by the standard BS7910 proved to be closest to the actual values than the standard ASME, Section XI, Appendix A. The most critical crack size was accepted by the criteria of the BS7910 and approved only on emergency condition of ASME Section XI, Appendix A.

No description available.

No description available.

A 20 litre experimental batch and continuous test rig and 5 litre batch and 50 litre continuous test rigs for stirred ball milling were built at the University of Natal and Mintek respectively. All the mills featured a grinding vessel with a central shaft equipped with pins and a torque measurement system. A washed chrome sand from the Bushveld Igneous Complex was used for the grinding experiments. Particle size analysis of products was performed using standard sieves and a Malvern Particle Sizer. Batch tests were run in the 20 litre stirred ball mill to achieve efficient grinding conditions. The effects of grinding conditions such as pulp density, media size, media density and shaft rotation speed and mill design parameters such as ball load, pin spacing and pin diameter on product size, power consumption and media wear were studied. It has been shown that the median size of the product can be calculated by the Charles' Energy-Size Equation. The stirred ball mill has been found to be more energy efficient than the tumbling ball mill. An energy reduction of 50% was possible for a product size of 6 microns when the stirred ball mill was employed instead of the tumbling ball mill. The energy input per ton of grinding media in the stirred ball mill could be 10 times higher than for the tumbling ball mill. Although during coarse grinds the media wear was higher in the stirred ball mill than in the tumbling mill, it became less so as grinding proceeded and for a product median size of 4.8 microns it was the same. Using a 5 litre batch mill, an experimental programme was designed to study the comminution characteristics of the stirred mill. A factorial design was prepared with the following parameters, which influence grinding in the stirred ball mill: pulp density, pin tip velocity and ball density and size. The energy required for grinding the chromite sand in the stirred ball mill was determined by the use of Charles' Equation. The findings were in agreement with the results predicted by this equation. It was shown that the Rosin-Rammler size distribution equation was a suitable procedure for presenting and comparing grinding data obtained from the stirred ball mill. The factors that had the greatest effect on grindability were, in order of importance: ball size, pin tip velocity and ball density. Interactions between grinding parameters were negligible. results implied that accurate predictions can be made to determine the grinding conditions required to achieve a desired product specification. An attempt was made to study the grinding kinetics the chromite are using the mass population·balance model. Grinding tests were performed with two mono size fractions ·53+38 and -38+25 microns and natural feed ·100 microns using various pin tip velocities, ball densities and within the normal stirred ball milling operating range. relationship between the ball diameter and the particle was explained by the "angle of nip" theory which applied for roller crushers. It was shown that the particle giving the maximum breakage rate was directly proportional to the ball diameter. Estimated grinding kinetic parameters from monosize provided a good basis for predictions of natural feed. However, the breakage rate obtained from monosize tests appeared to be lower than those from the natural feed It was found that if the selection and breakage functions were determined by monosize tests, it was possible to modify selection function parameters by back-calculation which gave the best fit to the natural feed size. A good correlation was obtained between the experimental and product distributions using a population-balance model. The links between the empirical model combining Charles' and Rosin-Rammler equations and the first-order batch grinding equation were also shown. The stirred ball mills were operated in batch and continuous mode. The median size of the products from the batch stirred ball mill experiments closely matched those of the continuous grinding experiments under similar grinding conditions. Using a salt solution as a tracer material, an attempt was made to estimate the residence time distribution based on a simplified analysis of the motion of the water in tile mill. The current scale-up methods for the stirred ball mill are discussed. A torque model was developed for given shaft geometry and ball relating the power rements of the stirred ball mill to the following prime design and operating parameters : mill diameter, mill height, pin tip velocity and effective density of the mill load. The basic assumptions underlying the model were that the mill content behaved as a fluidised bed, consequently a P effg h type model for the pressure was applied throughout the grinding media bed the effective charge velocity was proportional to the pin tip velocity. It was found that pin spacing, pin diameter and ball diameter significantly affected the mill torque. A semi-empirical torque model was derived to include these parameters. The relationships formulated from these models were shown to be in excellent agreement with experimental results. / Thesis (Ph.D.)-University of Natal, Durban, 1993.

In previous studies, the analysis of ball mill operating parameters and their effects on breakage phenomena has been limited to homogeneous materials. Though these studies have proven to be an asset in predictions of product size distributions and mill scale-up, they have not addressed the primary role of grinding, i.e. liberation. The present investigation analyzes the effect of ball mill operating parameters on the breakage rates of both liberated and composite material. The operating parameters studied include mill rotational speed, ball size, mill charge, and wet versus dry grinding. Breakage rates have been determined experimentally utilizing a SEM-IPS image analyzer. The mineral sample used was acquired from ASARCO's Young Mine which is located in Jefferson City Tennessee. It was a binary ore consisting of sphalerite and dolomite. Batch grinding experiments were conducted to provide breakage rates for the various composition classes. Breakage rates were then normalized with respect to energy to see if the changes in breakage rates associated with mill operating parameters were due to changes in breakage kinetics, or simply a function of energy input. The energy normalized data indicates that the free dolomite breakage rates tend to normalize with respect to energy in the case of varying interstitial fillings. Furthermore, changes in mill rotational speed tend to provide energy normalizable breakage rates for both free dolomite and sphalerite. In all other cases, analysis of the breakage rates and energy-specific breakage rates indicate that a change in breakage kinetics may be occurring. In general, particles containing a high proportion of sphalerite are more apt to break under impact conditions. On the other hand, particles containing a large proportion of dolomite were found to prefer attrition breakage conditions. / Master of Science / incomplete_metadata

The objective of this study was to improve the operation of the classical semiautogenous and ball milling circuit also known as the SABC circuit. In order to achieve this goal, the challenges around this circuit were identified as the formation of critical sized material in a SAG mill. The size class considered for the critical sized material also known as pebbles was -100+23 mm. The attainable region (AR) method was used as an optimisation technique for the generated results using a computer simulation programme. MODSIM® demo version 3.6.22 is ore processing simulator that was used. The research was divided into two sections, the first being the variation of feed flow rate ranging from 50 – 150 tph and ore feed size ranging between 100 and 600 mm. The second section compared the variation of the operating parameters of the SAG mill, which were mill filling, ball filling, ball size and mill speed. The AR technique graphically presented the results which indicated the best operating conditions to minimise pebble formation. The effects of mill filling on a SAG mill indicate that a higher filling produces lower pebbles. Lower pebble generation also was observed at a higher ball filling. The influence of ball size indicated that the larger ball size was more effective in the reduction of pebbles. For mill speed the media displayed two common mode operations namely cascading at a low speed of 65% and cataracting at higher speed of 75%. The higher speed generated the least pebbles. / College of Engineering, Science and Technology / M. Tech. (Chemical Engineering)

This study investigated the influence of the attainable region technique to ball milling as applied in reactor technology. Flow rate, ball filling, mill speed, ball size and mill density were varied. When each was varied, the rest of the parameters were kept constant in-order to determine the influence of each parameter on the process of milling. Selection function and breakage function parameters were selected for the mill model. These were kept constant for all four circuit configurations: open milling circuit, normal closed circuit, reverse closed circuit, and combined closed circuit. Flow rate was varied from 10 tph to 150 tph. It was observed that in all circuit configurations the optimum results were obtained from 90 tph upwards. When ball filling was varied, the optimum results were obtained between 30 % and 40 % of ball filling. At this range the mill is neither experiencing under-filling nor over-filling. When the mill speed was varied, at 60 – 80 % of critical speed the product specification was achieved and for grinding balls, sizes of between 60 mm and 90 mm yielded the optimum results. Varying the mill density resulted in insignificant changes. From the results, the combined closed circuit produced more of the product specification. / School of Engineering / M. Tech. (Engineering: Chemical)