Crystallization of fesoterodine fumarate active pharmaceutical ingredient: Modelling of thermodynamic equilibrium, nucleation, growth, agglomeration and dissolution kinetics and temperature cycling

Trampuž, Marko; Teslić, Dušan; Likozar, Blaž

doi:10.1016/j.ces.2019.02.019

Cited by 36 publications

(71 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The supersaturation lnS was extremely high (Figure 3c). The homogeneity of crystalline particles was low because a high supersaturation condition caused rapid nucleation and agglomeration [25]. From this result, the continuous operation in which high supersaturation occurred was inappropriate as an operation method for controlling comprehensive uniformity.…”

Section: Resultsmentioning

confidence: 99%

Operation Design of Reaction Crystallization Using Homogeneity Evaluation for the Quality Improvement of Agglomerated Crystalline Particles

2021

View full text Add to dashboard Cite

In the quality control of crystalline particles, the uniformity of the distribution of each characteristic, such as size and shape, is important. In particular, the problem in reaction crystallization is that the comprehensive uniformity of characteristic distributions is frequently reduced by the agglomeration phenomena. In this study, we designed an operation method to improve the comprehensive uniformity in a liquid–liquid reaction crystallization by evaluating the dynamic variation in the uniformity of particle size and crystal shape using homogeneity. The homogeneity of final particles increased when the supersaturation was lowered by intermittent operation with inner seed production. Since the ratios of the uniformities of particle sizes and crystal shapes constituting homogeneity varied dynamically, the intermittent operation was designed by focusing on individual uniformities. The uniformity of particle size for the final particles was increased via modulation operation using reverse addition for the dissolution of the microparticles. In the growth stage after the reverse addition, the uniformity of the shape of the final particles was increased by raising the number of times of adding solution for decreasing the supersaturation. In addition, we proposed suitable addition methods to improve comprehensive uniformity by controlling uniformity constituting homogeneity at each stage of intermittent operation.

show abstract

Section: Resultsmentioning

confidence: 99%

Operation Design of Reaction Crystallization Using Homogeneity Evaluation for the Quality Improvement of Agglomerated Crystalline Particles

2021

View full text Add to dashboard Cite

show abstract

“…The FBRM measuring range was 0-1000 μm and was divided into 100 equal parts by a linear scale. Not the CSD but the chord length distribution (CLD) can be directly determined by FBRM [17][18][19]. However, the CLD can be converted into the CSD with statistical methods via a mapping matrix based on the crystal shape [20][21][22].…”

Section: Substances and Devicesmentioning

confidence: 99%

Partial Seeding Policy for Controlling the Crystal Quality in Batch Cooling Crystallization

Unno

Hirasawa

2020

Chem Eng & Technol

View full text Add to dashboard Cite

Partial seeding, in which the nuclei originating from seed crystals grow to yield the product crystals, was simulated and optimized for controlling the batch cooling crystallization process of L-arginine. The product quality was evaluated by the coefficient of variation (CV) of the crystal size distribution. First, the optimum seed amount for partial seeding was estimated by simulation. Then, the simulated values of the optimum seed amount and the resulting local minimum CV were correlated with the seed crystal size and the cooling rate. The correlation can be utilized for estimating the seed amount in the case that the seed crystals are added in a slurry. Finally, these simulated values were compared to the measured ones. Consequently, the optimum seed amount was suggested to be reasonably predicted.

show abstract

“…Because the density of paracetamol crystals is already reported, 54 measured crystal size and mass can provide the shape factor, via Equation (18). As shown in Figure 6, the mass and number of sieved crystals were measured to estimate the shape factors.…”

Section: Solubility Of Paracetamol In Ethanolmentioning

confidence: 99%

“…In this study, a full population balance model (PBM) is used to describe the crystallization in a batch process. While many studies have examined primary nucleation, secondary nucleation and growth, [14][15][16][17][18] few modeling studies involving disappearance of crystals are found in the literature. 3,19,20 Most PBMs cannot be solved analytically except for very simple cases.…”

Section: Introductionmentioning

confidence: 99%

Modeling of Nucleation, Growth, Dissolution, and Disappearance of Paracetamol in Ethanol Solution for Unseeded Batch Cooling Crystallization with Temperature-Cycling Strategy

Kim¹,

Kawajiri²,

Rousseau³

et al. 2020

Preprint

View full text Add to dashboard Cite

A population balance model (PBM) is developed for unseeded batch crystallization, with temperature-cycling strategies to control the crystal size distribution. The model is able to predict the evolution of crystal size distributions of crystallizing paracetamol from ethanol solutions considering the characteristics of primary nucleation, secondary nucleation, growth, dissolution, and disappearance of crystals. Process analytical technology (PAT) tools were employed to collect solute concentration data and crystal size distribution data. This model employs a boundary condition to describe the disappearance of crystals in temperature-cycling strategies where the temperature is increased and decreased repeatedly. As a result, the obtained model can describe the evolution of crystal size distribution when repetition of cooling and heating is carried out. Moreover, this model can be applied to investigate phenomena that are challenging to explain with experimental data alone, thereby we can gain insight and optimize the operation of the process.

show abstract

Crystallization of fesoterodine fumarate active pharmaceutical ingredient: Modelling of thermodynamic equilibrium, nucleation, growth, agglomeration and dissolution kinetics and temperature cycling

Cited by 36 publications

References 27 publications

Operation Design of Reaction Crystallization Using Homogeneity Evaluation for the Quality Improvement of Agglomerated Crystalline Particles

Operation Design of Reaction Crystallization Using Homogeneity Evaluation for the Quality Improvement of Agglomerated Crystalline Particles

Partial Seeding Policy for Controlling the Crystal Quality in Batch Cooling Crystallization

Modeling of Nucleation, Growth, Dissolution, and Disappearance of Paracetamol in Ethanol Solution for Unseeded Batch Cooling Crystallization with Temperature-Cycling Strategy

Contact Info

Product

Resources

About