Effect of different variables in the solubility of ampicillin and corresponding solid phase

Bezerra, I. M.; Moreira, L.C.; Chiavone‐Filho, Osvaldo; Mattedi, Silvana

doi:10.1016/j.fluid.2017.11.033

Cited by 6 publications

(3 citation statements)

References 28 publications

(49 reference statements)

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“…Ampicillin has limited chemical stability at pH ≤ 5, below which degradation products are formed . Batch enzymatic reactor effluents for ampicillin synthesis are typically around pH = 6.0–6.5. , It is preferred that ampicillin crystallization occurs at pH < 8 to ensure that it crystallizes in the desired trihydrate polymorph and to avoid excessive supersaturations inducing uncontrolled nucleation resulting in broad size distributions. The third constraint (eq ) ensures that a minimum target amount of ampicillin has been crystallized from solution, which varies between the considered experimental cases; considered values and their corresponding crystallization yields are shown in Table .…”

Section: Methodsmentioning

confidence: 99%

“…28 Batch enzymatic reactor effluents for ampicillin synthesis are typically round pH = 6.0-6.5. 29,30 It is preferred that ampicillin crystallization occurs at pH < 8 to ensure it crystallizes in the desired trihydrate polymorph 31 and to avoid excessive supersaturations inducing uncontrolled nucleation resulting in broad size distributions. The third constraint (eq.…”

Section: Dynamic Optimization 231 Problem Formulationmentioning

confidence: 99%

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Multiobjective Dynamic Optimization of Ampicillin Batch Crystallization: Sensitivity Analysis of Attainable Performance vs Product Quality Constraints

Dafnomilis

Diab

Rodman

et al. 2019

Ind. Eng. Chem. Res.

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Ampicillin is a broad spectrum antibiotic and World Health Organization Essential Medicine whose crystallization is an essential unit operation in its production. A published model for the solubility of ampicillin as a function of pH as well as growth and nucleation kinetics allows for dynamic simulation and optimization of its batch crystallization. While experimental approaches to investigating different dynamic pH profiles have been considered in the literature, dynamic mathematical optimization of pH modulations to meet specific production objectives for ampicillin batch crystallization has yet to be implemented; therein lies the novelty of this study. This work performs dynamic simulation and optimization of the batch crystallization of ampicillin to establish optimal pH trajectories for different production objectives. Simulation of already published batch seeded ampicillin crystallization experiments is performed prior to definition and solution of a dynamic optimization problem for maximization of mean crystal sizes and minimization of size distribution width. The effects of seed loading, time domain discretization and mean crystal size and size distribution width objective function weights are considered and discussed. Pareto fronts showing tradeoffs between different objectives and constraints are then investigated.

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Section: Methodsmentioning

confidence: 99%

Section: Dynamic Optimization 231 Problem Formulationmentioning

confidence: 99%

Multiobjective Dynamic Optimization of Ampicillin Batch Crystallization: Sensitivity Analysis of Attainable Performance vs Product Quality Constraints

Dafnomilis

Diab

Rodman

et al. 2019

Ind. Eng. Chem. Res.

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show abstract

“…The second constraint (Eq. 14) ensures the pH is not too low (causing ampicillin degradation) or high (forming undesirable non-trihydrate ampicillin polymorphs); ampicillin has limited chemical stability at pH ≤ 5, below which degradation products are formed, and undesired nontrihydrate polymorphs are formed at pH > 8 (Bezerra et al, 2018). The third constraint (Eq.…”

Section: Dynamic Optimisation Problem Formulationmentioning

confidence: 99%

Multi-objective Dynamic Optimisation of Ampicillin Batch Crystallisation

Dafnomilis

Diab

Rodman

et al. 2020

Computer Aided Chemical Engineering

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Ampicillin is a key β-lactam antibiotic listed as a World Health Organisation (WHO) Essential Medicine. Crystallisation is a unit operation of paramount importance in pharmaceutical manufacturing, whose design and operation are essential in controlling process yield and important product quality attributes, such as mean product crystal size (MCS) and size distribution width. A published model for the solubility of ampicillin as a function of pH as well as growth and nucleation kinetics is used towards the simulation and optimisation of its batch crystallisation. This study performs multi-objective dynamic optimisation of the batch crystallisation of ampicillin to establish optimal pH trajectories for different production objectives, including maximising the mean crystal size whilst minimising the size distribution width subject to various yield constraints. Trade-offs between different product quality attributes are thus quantified, visualised and discussed.

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Characterization and Thermodynamic Behavior of Protein Adsorption on a Macroporous Monolithic Polymeric IMAC Matrix

et al. 2023

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Effect of different variables in the solubility of ampicillin and corresponding solid phase

Cited by 6 publications

References 28 publications

Multiobjective Dynamic Optimization of Ampicillin Batch Crystallization: Sensitivity Analysis of Attainable Performance vs Product Quality Constraints

Multiobjective Dynamic Optimization of Ampicillin Batch Crystallization: Sensitivity Analysis of Attainable Performance vs Product Quality Constraints

Multi-objective Dynamic Optimisation of Ampicillin Batch Crystallisation

Characterization and Thermodynamic Behavior of Protein Adsorption on a Macroporous Monolithic Polymeric IMAC Matrix

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