Determination of crystal growth rate for porcine insulin crystallization with CO2 as a volatile acidifying agent

Integrated Continuous Crystallization and Spray Drying of Insulin for Pulmonary Drug Delivery

“…The small mean particle size at the lowest tested initial concentration was consistent with a lack of crystal growth. It has been reported that, in a stirred tank, the linear growth rate of insulin crystals is proportional to ( C / C s ) 2.9 where C is the actual concentration . Our results also suggested a rapid drop in growth rate when the solution concentration was decreased.…”

“…The solubility data from our measurements showed a similar trend and were of the same order of magnitude when they were compared to literature solubility data. 46,47 The solubility measurements demonstrated that the pH can greatly alter the supersaturation in the tested range, which provided the basis of the design of the crystallization experiments described next.…”

Modelling Crystallization: When the Normal Growth Velocity Depends on the Supersaturation

“…The time to achieve the inflection point could be used for non-dimensionalization of a model, logistic [41] or JMAKn [33]. (31) In the form of an expression, ( 31) is presented as:…”

“…One of the conditions for this to be fulfilled is N to be small in order to not allow for the overlapping of the concentration fields around each of the growing crystals [24] and while the diffusion is slow (compared to the growth kinetics), hence 1 g  , this is more likely to happen. For example, when the diffusion of the incorporating units is slow a priori, as in the case of protein crystallization, 1 g  is preserved along almost the whole range of studied supersaturations, see [31] (after linearization of the axes of their figure 4, otherwise the authors obtained 3 g  in log-log coordinates fitting through the whole range of points). Thus, an additional constraint in our model is on the value of g -it remains fixed throughout the whole process.…”