Morphological population balance modelling of the effect of crystallisation environment on the evolution of crystal size and shape of para-aminobenzoic acid

A current morphological population balance (MPB) modelling methodology, which integrates crystal morphology, facet growth kinetics with multi-dimensional population balance, is overviewed and demonstrated, hence providing an attractive approach for modelling crystallisation processes. MPB modelling is applied to simulate the batch crystallisation of the alpha-form of para-aminobenzoic acid from ethanolic solutions as a function of the crystallisation environment including cooling rate, seeding temperature and seed conditions (loading, size and shape). The evolution of crystal shape/size and their distributions revealed that higher loading led to smaller and less needle-like crystals with similar yields, hence potentially being an important parameter for process control. Examination of the development of the fracture surface for broken seeds, mimicking the seed conditions after milling in practice in the simulated processes, demonstrated that these faces grew fast and then rapidly disappeared from the external crystal morphology. Restriction and challenges inherent in the current model are also highlighted

Measurement, modelling, and closed-loop control of crystal shape distribution: Literature review and future perspectives

Crystal morphology is known to be of great importance to the end-use properties of crystal products, and to affect down-stream processing such as filtration and drying. However, it has been previously regarded as too challenging to achieve automatic closed-loop control. Previous work has focused on controlling the crystal size distribution, where the size of a crystal is often defined as the diameter of a sphere that has the same volume as the crystal. This paper reviews the new advances in morphological population balance models for modelling and simulating the crystal shape distribution (CShD), measuring and estimating crystal facet growth kinetics, and two- and three-dimensional imaging for on-line characterisation of the crystal morphology and CShD. A framework is presented that integrates the various components to achieve the ultimate objective of model-based closed-loop control of the CShD. The knowledge gaps and challenges that require further research are also identified

Investigating the Effects of Progesterone Levels and Corpus Luteum Mass on Fecundity in Obese and Healthy Females

As the global overweight and obesity populations increase, obesity-related health outcomes are also on the rise. Amongst such health outcomes are the negative implications on female reproductive health, i.e., reduced fertility within obese females. Specifically, the relationship between obesity, fecundity, and progesterone levels via corpus luteum are of great interest. Our study investigated the differences in progesterone and corpus luteum (CL) mass between healthy and obese human females. A virtual sample of 12 females at varying ages (19, 28, 37) was created via HumMod. Then, progesterone levels and CL mass were measured on day 15, 22, and 29 of the menstrual cycle, which encompasses the luteal phase. Progesterone levels and CL mass were higher in healthy females on day 15 of the menstrual cycle, and conversely, higher in obese females on day 22 and 29 of the menstrual cycle. Unexpectedly, the higher levels of CL mass and progesterone secretion in obese females suggest this anomaly might play a role in the obesity associated infertility via a multitude of factors (i.e., impaired embryo implantation or low estradiol). Due to the effect that other factors can have on fertility such as co-occurring hormone levels and physical activity, our research serves as a basis to investigating those areas further. Thus, further research is needed to determine why infertility is more prominent in obese females in order to develop an adequate intervention for this on-the-rise issue

Interesting Morphological Behavior of Organic Salt Choline Fenofibrate: Effect of Supersaturation and Polymeric Impurity

Crystal habit of drug molecules can have significant influence on the processing and performance of pharmaceutical products. During the development of Trilipix, a pharmaceutical product used for the treatment of mixed dyslipidemia, several crystal habits were observed for the active ingredient choline fenofibrate. The dissolution and performance of the drug product were not impacted by changes in crystal habit of the active ingredient due to high solubility of the drug. However, the formulation process was impacted by variations in crystal habit of the active ingredient, requiring robust control of the crystal habit. The crystal habit was greatly influenced by supersaturation during crystallization from a mixed solvent system comprising methanol and isopropanol. In addition to supersaturation, trace levels of a polymeric impurity in the starting material fenofibrate had a detrimental effect on the crystal habit. This article discusses the effects of these factors on the crystal habit of choline fenofibrate and the design of a crystallization process to deliver the target crystal habit, most suited to the formulation process. The article also provides preliminary mechanistic insights into the crystal habit of this organic salt using an extension of the spiral growth model for morphology prediction of organic molecular crystals. An attempt is made to explain the effect of supersaturation and impurity on the crystal habit of choline fenofibrate using the concepts of stability of surfaces, building units, periodic bond chain theory, and the spiral growth model

Correction to Interesting Morphological Behavior of Organic Salt Choline Fenofibrate: Effect of Supersaturation and Polymeric Impurity

Correction to Interesting Morphological Behavior of Organic Salt Choline Fenofibrate: Effect of Supersaturation and Polymeric Impurit