Surface-induced crystallization of pharmaceuticals and biopharmaceuticals: A review

Artusio, Fiora; Pisano, Roberto

doi:10.1016/j.ijpharm.2018.05.069

Cited by 71 publications

(54 citation statements)

References 148 publications

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“…To summarize, the films obtained with the BAMS procedure showed the presence of well oriented α-phase only. Examples of surfaces stabilizing selectively a polymorphic modification are now numerous [47,48,[52][53][54][55][56], but less common is combination of selectivity and a high degree of iso-orientation.…”

Section: Thioindigo Film Characterizationmentioning

confidence: 99%

Crystal alignment of surface stabilized polymorph in thioindigo films

et al. 2020

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Thioindigo (2-(3-Oxo-1-benzothiophen-2(3H)-ylidene)-1-benzothiophen-3(2H)-one) is a synthetic dye related to the natural compound Indigo. Notwithstanding the interest aroused recently by its employment as a functional material in a number of applications, a satisfactory characterization of its solid state is still missing. In this work, we study the occurrence of the two thioindigo α and β polymorphs under various growth conditions, and find that their structural similarity implies they often coexist. However, whereas polymorph β is certainly predominant in the bulk phase, polymorph α grows preferentially on substrates, turning out to be the surface stabilized phase in highly homogeneous and ordered films obtained by the bar-assisted meniscus shearing method (BAMS). DFT calculations support the experimental findings, aiding in the polymorph spectroscopic identification and to the interpretation of the order in the films of polymorph α.

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Section: Thioindigo Film Characterizationmentioning

confidence: 99%

Crystal alignment of surface stabilized polymorph in thioindigo films

et al. 2020

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“…[1][2][3] Many approaches have been proposed to control polymorphism, including solvents, concentration, temperature, control of supersaturation profiles, additives and interfaces. 1,2,[4][5][6] Initial crystallisation screening and process development is often performed at small scale where mixing and agitation is ill-defined or even absent and therefore these effects are often underestimated or overlooked. However, there are numerous examples where agitation plays profound role in determining polymorphic outcome in crystallisation of pharmaceuticals and other molecular systems, such as carbamazepine, stearic acid, L-glutamic acid, m-hydroxybenzoic acid 7 or glycine.…”

Section: Introductionmentioning

confidence: 99%

Conundrum of γ glycine nucleation revisited: to stir or not to stir?

et al. 2019

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Glycine polymorphism presents a conundrum: while the metastable α form of glycine typically crystallises in bulk cooling crystallisation from aqueous solution, both the highly unstable β and stable γ forms can be selectively crystallised in small scale cooling or evaporative experiments, without any additives, cosolvents or external fields. Small scale experiments in microwells or droplets differ from bulk crystallisation in some key aspects: absence of agitation, presence of large (and often very particular) surface areas per crystallisation volume, and ability to reach very high supersaturations. In this work we investigated effects of agitation on polymorphic outcomes in glycine crystallisation from aqueous solutions across a wide range of supersaturations at mL scale under quiescent conditions with and without a PTFE-coated magnetic stirrer (without any stirring) as well as under stirred conditions (with agitation supplied by the stirrer). In the absence of stirring, γ was predominant at higher glycine concentrations, which indicates that γ is more likely to nucleate than α in highly supersaturated aqueous solutions under quiescent conditions. Intriguingly, we found that under stirred conditions α was predominant at all concentrations and temperatures investigated. The effect of stirring on the preference for α glycine polymorphism cannot be fully explained by secondary nucleation alone. Instead, primary nucleation of glycine (at least of metastable forms) is strongly enhanced by stirring, in agreement with previous observations of shear effect on primary nucleation of glycine, and it is likely that similar effects play a role in other polymorphic systems of pharmaceutical interest. † Raw data is available open access through the following DOI: https://doi.org/ 10.15129/9a4ec7f5-fe41-4ec2-92ef-a9abca03b217 ‡ Electronic supplementary information (ESI) available: Contains information about quenched cooling experiments and movement induced nucleation. See

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“…The form of a drug obtained during crystallization depends on several factors including temperature, freezing rate, solvent, and concentration [ 4 , 34 , 65 , 66 ]. In order to minimize some of these effects, there has been a shift towards more controllable drug crystal engineering processes such as heterogeneous crystallization onto tailored surfaces and confined crystallization within pores [ 27 , 31 , 67 , 68 , 69 ].…”

Section: Individual Approaches To Polymorph Controlmentioning

confidence: 99%

“…Additionally, while some reviews have presented the current state of studies relating to heterogeneous crystallization from surfaces [ 27 , 28 ] and crystallization within nanopores [ 29 , 30 , 31 ], this review focuses on studies using a combination of these methods to tailor the drug form. We first introduce polymorphism in Section 2 , then discuss heterogeneous crystallization and crystallization under confinement in Section 3 and Section 4 to provide a strong context for Section 5 , which reviews the state of the art on combined approaches to controlling crystallization.…”

Section: Introductionmentioning

confidence: 99%

Combining Surface Templating and Confinement for Controlling Pharmaceutical Crystallization

Banerjee

Brettmann

2020

Pharmaceutics

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Poor water solubility is one of the major challenges to the development of oral dosage forms containing active pharmaceutical ingredients (APIs). Polymorphism in APIs leads to crystals with different surface wettabilities and free energies, which can lead to different dissolution properties. Crystal size and habit further contribute to this variability. An important focus in pharmaceutical research has been on controlling the drug form to improve the solubility and thus bioavailability of APIs. In this regard, heterogeneous crystallization on surfaces and crystallization under confinement have become prominent forms of controlling polymorphism and drug crystal size and habits; however there has not been a thorough review into the emerging field of combining these approaches to control crystallization. This tutorial-style review addresses the major advances that have been made in controlling API forms using combined crystallization methods. By designing templates that not only control the surface functionality but also enable confinement of particles within a porous structure, these combined systems have the potential to provide better control over drug polymorph formation and crystal size and habit. This review further provides a perspective on the future of using a combined crystallization approach and suggests that combining surface templating with confinement provides the advantage of both techniques to rationally design systems for API nucleation.

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Surface-induced crystallization of pharmaceuticals and biopharmaceuticals: A review

Cited by 71 publications

References 148 publications

Crystal alignment of surface stabilized polymorph in thioindigo films

Crystal alignment of surface stabilized polymorph in thioindigo films

Conundrum of γ glycine nucleation revisited: to stir or not to stir?

Combining Surface Templating and Confinement for Controlling Pharmaceutical Crystallization

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