Special Issue "Pharmaceutical Crystallisation Science and Engineering"

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (30 November 2017)

Special Issue Editors

Guest Editor
Dr. Mingzhong Li

Leicester School of Pharmacy, De Montfort University, Leicester, LE1 9BH, UK
Website | E-Mail
Interests: pharmaceutical co-crystallisation; crystallisation modelling and control; pre-formation development; particle sizing; multiphase flow modelling and computation
Guest Editor
Dr. Tariq Mahmud

School of Chemical and Process Engineering, University of Leeds, Leeds, LS2 9JT, UK
Website | E-Mail
Interests: crystallisation process engineering: Process development and scale up, monitoring and control, modelling; downstream processing: Filtatrion, washing and drying

Special Issue Information

Dear Colleagues,

Crystallisation plays an essential role in the pharmaceutical industry, in which it is, not only used to isolate and purify Active Pharmaceutical Ingredients (APIs), but also offers a molecular approach to modify APIs in order to achieve desired properties, such as crystal size and shape, polymorphs, solvates, salts, and co-crystals. This requires careful design and optimisation of crystallisation processes. However, a significant gap in the knowledge exists for designing such optimal systems, in particular the relationship between the fundamentals of crystallisation kinetics, i.e., nucleation and crystal growth, with the observed performance and behaviour of the APIs. The aim of this Special Issue of Pharmaceutics journal is to provide a platform to report recent developmentof fundamental knowledge in pharmaceutical crystallisation science and engineering by researchers in the industry and academia from around the world. This Special Issue will focus on the crystallisation fundamentals including nucleation, crystal growth and structure; different types of crystals and their crystallisation environment; crystallisation modelling from molecular to process scales; and industrial crystallisation process development, scale up, measurement and control.

Prof. Dr. Mingzhong Li
Dr. Tariq Mahmud
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 550 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Fundamentals of nucleation and crystal growth
  • Types of crystals and crystallisation environment
  • Techniques for crystallisation characterisation
  • Crystallisation modelling across length scales
  • Industrial crystallisation processes
  • Pharmaceutical co-crystals
  • Crystallisation modelling and control

Published Papers (5 papers)

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Research

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Open AccessArticle Preventing Crystal Agglomeration of Pharmaceutical Crystals Using Temperature Cycling and a Novel Membrane Crystallization Procedure for Seed Crystal Generation
Pharmaceutics 2018, 10(1), 17; https://doi.org/10.3390/pharmaceutics10010017
Received: 4 December 2017 / Revised: 16 January 2018 / Accepted: 18 January 2018 / Published: 24 January 2018
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Abstract
In this work, a novel membrane crystallization system was used to crystallize micro-sized seeds of piroxicam monohydrate by reverse antisolvent addition. Membrane crystallization seeds were compared with seeds produced by conventional antisolvent addition and polymorphic transformation of a fine powdered sample of piroxicam
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In this work, a novel membrane crystallization system was used to crystallize micro-sized seeds of piroxicam monohydrate by reverse antisolvent addition. Membrane crystallization seeds were compared with seeds produced by conventional antisolvent addition and polymorphic transformation of a fine powdered sample of piroxicam form I in water. The membrane crystallization process allowed for a consistent production of pure monohydrate crystals with narrow size distribution and without significant agglomeration. The seeds were grown in 350 g of 20:80 w/w acetone-water mixture. Different seeding loads were tested and temperature cycling was applied in order to avoid agglomeration of the growing crystals during the process. Focused beam reflectance measurement (FBRM); and particle vision and measurement (PVM) were used to monitor crystal growth; nucleation and agglomeration during the seeded experiments. Furthermore; Raman spectroscopy was used to monitor solute concentration and estimate the overall yield of the process. Membrane crystallization was proved to be the most convenient and consistent method to produce seeds of highly agglomerating compounds; which can be grown via cooling crystallization and temperature cycling. Full article
(This article belongs to the Special Issue Pharmaceutical Crystallisation Science and Engineering)
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Graphical abstract

Open AccessArticle Solvation and Aggregation of Meta-Aminobenzoic Acid in Water: Density Functional Theory and Molecular Dynamics Study
Pharmaceutics 2018, 10(1), 12; https://doi.org/10.3390/pharmaceutics10010012
Received: 4 January 2018 / Revised: 18 January 2018 / Accepted: 19 January 2018 / Published: 23 January 2018
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Abstract
Meta-aminobenzoic acid, an important model system in the study of polymorphism and crystallization of active pharmaceutical ingredients, exist in water in both the nonionic (mABA) and zwitterionic (mABA±) forms. However, the constituent molecules of the polymorph that crystallizes from aqueous solutions
[...] Read more.
Meta-aminobenzoic acid, an important model system in the study of polymorphism and crystallization of active pharmaceutical ingredients, exist in water in both the nonionic (mABA) and zwitterionic (mABA±) forms. However, the constituent molecules of the polymorph that crystallizes from aqueous solutions are zwitterionic. This study reports atomistic simulations of the events surrounding the early stage of crystal nucleation of meta-aminobenzoic acid from aqueous solutions. Ab initio molecular dynamics was used to simulate the hydration of mABA± and mABA and to quantify the interaction of these molecules with the surrounding water molecules. Density functional theory calculations were conducted to determine the low-lying energy conformers of meta-aminobenzoic acid dimers and to compute the Gibbs free energies in water of nonionic, (mABA)2, zwitterionic, (mABA±)2, and nonionic-zwitterionic, (mABA)(mABA±), species. Classical molecular dynamics simulations of mixed mABA–mABA± aqueous solutions were carried out to examine the aggregation of meta-aminobenzoic acid. According to these simulations, the selective crystallization of the polymorphs whose constituent molecules are zwitterionic is driven by the formation of zwitterionic dimers in solution, which are thermodynamically more stable than (mABA)2 and (mABA)(mABA±) pairs. This work represents a paradigm of the role of molecular processes during the early stages of crystal nucleation in affecting polymorph selection during crystallization from solution. Full article
(This article belongs to the Special Issue Pharmaceutical Crystallisation Science and Engineering)
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Graphical abstract

Open AccessArticle A Comparative Study of Coupled Preferential Crystallizers for the Efficient Resolution of Conglomerate-Forming Enantiomers
Pharmaceutics 2017, 9(4), 55; https://doi.org/10.3390/pharmaceutics9040055
Received: 21 September 2017 / Revised: 13 November 2017 / Accepted: 23 November 2017 / Published: 5 December 2017
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Abstract
The separation of enantiomers is of great importance due to their possible differences in therapeutic properties. Preferential crystallization in various configurations of coupled batch crystallizers is used as an attractive means to separate the conglomerate-forming enantiomers from racemic mixtures. However, the productivity of
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The separation of enantiomers is of great importance due to their possible differences in therapeutic properties. Preferential crystallization in various configurations of coupled batch crystallizers is used as an attractive means to separate the conglomerate-forming enantiomers from racemic mixtures. However, the productivity of such batch processes can be limited by the nucleation of the counter enantiomer and consumption of the supersaturation. In this work, a recently proposed process configuration, which uses coupled mixed suspension mixed product removal (MSMPR) with liquid phase exchange, is investigated by simulation studies. A detailed study on the effect of process parameters (e.g., feed flow rate, seed mass, and liquid phase exchange) on the productivity and yield of the coupled MSMPR has been presented. Moreover, a comparison of various coupled crystallizer configurations is carried out. It is shown through simulation studies that the productivity of the enantiomeric separation can be significantly improved compared to the previously proposed batch modes when the continuous configuration is used. The effect of nucleation kinetic parameters on the performances of various crystallizer configurations is studied as well. A set of coupled population balance equations (PBEs) was used to describe the evolution of the crystal phase of the both enantiomers in each vessel. These equations were solved numerically using the quadrature method of moments. The insights obtained in this study will be useful in the process design of coupled crystallizer systems. Full article
(This article belongs to the Special Issue Pharmaceutical Crystallisation Science and Engineering)
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Open AccessArticle Preparation and Characterization of Carbamazepine Cocrystal in Polymer Solution
Pharmaceutics 2017, 9(4), 54; https://doi.org/10.3390/pharmaceutics9040054
Received: 1 October 2017 / Revised: 13 November 2017 / Accepted: 29 November 2017 / Published: 1 December 2017
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Abstract
In this study, we attempted to prepare carbamazepine (CBZ) cocrystal through the solution method in ethanol-water solvent mixture (volume ratio 1:1) and polyvinyl pyrrolidone (PVP) solution. Nicotinamide (NIC) and saccharin (SAC) were selected as cocrystal coformers. Cocrystal screening products were characterized by Fourier
[...] Read more.
In this study, we attempted to prepare carbamazepine (CBZ) cocrystal through the solution method in ethanol-water solvent mixture (volume ratio 1:1) and polyvinyl pyrrolidone (PVP) solution. Nicotinamide (NIC) and saccharin (SAC) were selected as cocrystal coformers. Cocrystal screening products were characterized by Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction (PXRD) techniques. Characterization results show that in ethanol-water solvent mixture, pure CBZ-NIC cocrystal can be prepared, while CBZ-SAC cocrystal cannot be obtained. The addition of PVP can inhibit CBZ-NIC cocrystal formation and facilitate CBZ-SAC cocrystal formation. Full article
(This article belongs to the Special Issue Pharmaceutical Crystallisation Science and Engineering)
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Review

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Open AccessReview Pharmaceutical Cocrystals: New Solid Phase Modification Approaches for the Formulation of APIs
Pharmaceutics 2018, 10(1), 18; https://doi.org/10.3390/pharmaceutics10010018
Received: 29 November 2017 / Revised: 2 January 2018 / Accepted: 10 January 2018 / Published: 25 January 2018
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Abstract
Cocrystals can be used as an alternative approach based on crystal engineering to enhance specific physicochemical and biopharmaceutical properties of active pharmaceutical ingredients (APIs) when the approaches to salt or polymorph formation do not meet the expected targets. In this article, an overview
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Cocrystals can be used as an alternative approach based on crystal engineering to enhance specific physicochemical and biopharmaceutical properties of active pharmaceutical ingredients (APIs) when the approaches to salt or polymorph formation do not meet the expected targets. In this article, an overview of pharmaceutical cocrystals will be presented, with an emphasis on the intermolecular interactions in cocrystals and the methods for their preparation. Furthermore, cocrystals of direct pharmaceutical interest, along with their in vitro properties and available in vivo data and characterization techniques are discussed, highlighting the potential of cocrystals as an attractive route for drug development. Full article
(This article belongs to the Special Issue Pharmaceutical Crystallisation Science and Engineering)
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