The Predictably Elusive Form II of Aspirin

Vishweshwar, Peddy; McMahon, Jennifer A.; Oliveira, Mark A.; Peterson, Matthew L.; Zaworotko, Michael J.

doi:10.1021/ja056455b

Cited by 326 publications

(268 citation statements)

References 36 publications

Supporting

Mentioning

251

Contrasting

Unclassified

Order By: Relevance

“…Molecular crystals have increasingly attracted great attention due to their peculiar chemical and physical properties, which make them suitable as high energy-density materials, [1][2][3] active pharmaceutical ingredients (APIs), [4][5][6] constituents of opto-electronic devices for their linear and non-linear optical properties, [7][8][9] etc.…”

mentioning

confidence: 99%

Thermal properties of molecular crystals through dispersion-corrected quasi-harmonic ab initio calculations: the case of urea

2016

View full text Add to dashboard Cite

An ab initio quantum-mechanical theoretical framework is presented to compute the thermal properties of molecular crystals. The present strategy combines dispersion-corrected density-functional-theory (DFT-D), harmonic phonon dispersion, quasi-harmonic approximation to the lattice dynamics for thermal expansion and thermodynamic functions, and quasi-static approximation for anisotropic thermoelasticity. The proposed scheme is shown to reliably describe thermal properties of the urea molecular crystal by a thorough comparison with experimental data.Molecular crystals have increasingly attracted great attention due to their peculiar chemical and physical properties, which make them suitable as high energy-density materials, 1-3 active pharmaceutical ingredients (APIs), 4-6 constituents of opto-electronic devices for their linear and non-linear optical properties, 7-9 etc.Nonetheless, from a theoretical view-point, they still represent a major challenge to the state-of-the-art quantum-chemical methods as many kinds of chemical interactions (covalent intra-molecular, electrostatic, hydrogen-bond, long-range dispersive) need to be accurately described simultaneously. Only in recent years, have different theoretical approaches been devised in order to predict their structural and energetic properties (with the main goal of discriminating between competing polymorphs): from force-field to high-level molecular fragment-based schemes, from periodic dispersion-corrected density functional theory (DFT-D) to periodic many-body wave-function techniques. [10][11][12][13][14][15][16][17][18] However, once a reliable and balanced description of the various chemical interactions has been achieved by means of any of the above-mentioned quantum-chemical methods, the extension of their applicability to more complex properties of technological and industrial relevance, which would greatly increase their predictiveness, such as mechanical, elastic, optical and thermodynamic responses, [19][20][21][22] has to be performed. Apart from the intrinsic high degree of complexity of the required theoretical techniques and algorithms, the main difficulty here is represented by the fact that most of those properties are largely affected by thermal effects, 23-25 even at room temperature, such as zero-point energy, harmonic and anharmonic thermal nuclear motion, thermal lattice expansion, etc.Most quantum-chemical ab initio methods describe the groundstate of a system at zero pressure and temperature. If the inclusion of pressure in the computed structural and elastic properties is a relatively easy task, 16,[26][27][28] this is definitely not the case when temperature has to be accurately accounted for. Indeed, we are still far from having effective schemes formally developed and efficiently implemented in a solid state context, particularly so when anharmonic terms to the lattice potential have to be included into the formalism. When the harmonic approximation (HA) to the lattice potential is used, the vibrational contribution to the free ene...

show abstract

mentioning

confidence: 99%

Thermal properties of molecular crystals through dispersion-corrected quasi-harmonic ab initio calculations: the case of urea

2016

View full text Add to dashboard Cite

show abstract

“…However, increasing amount of literature is also available either to describe the precipitation behavior of this drug during pre-and post-formulation stages or to illustrate the conversion from amorphous to crystalline or vice versa within the dosage form itself. Polymorphism of aspirin crystals has recently become an important issue, following reports of a second polymorph by Vishweshwar et al (15) and Almarsson et al (16). Although the two different polymorphs (form I and form II) of ASP crystals have been existed, the mysterious metastable form II (but pure and therapeutically effective one) has a tendency to grow within the crystals of stable form I as intergrowths (17).…”

Section: Resultsmentioning

confidence: 99%

“…Recently, Jafari et al (22) have also investigated the capability of the gas antisolvent (GAS) process to produce the therapeutically effective aspirin particles by studying the effect of four operating parameters namely, antisolvent addition, process temperature, solute concentration, and solvent type (methanol and acetone) on the final product particle size distribution, morphology, and crystallinity. Furthermore, the elusive form II of aspirin has been obtained during co-crystallization experiments of aspirin with levetiracetam or acetamide in acetonitrile after heating this solution at 70°C followed by slow evaporation of this homogeneous solution over 2 days (15,16). Collectively, all these studies indicated that depending on the experimental conditions applied at the time of their screening/ preformulation stage, the formation of pure or therapeutically effective form of crystalline API might have been occurred.…”

Section: Resultsmentioning

confidence: 99%

“…Peaks observed from the analysis were identical to those observed at diffraction angles of the reference pattern for aspirin as shown in the standard pharmacopoeias. The ASP-I crystal showed a sharp diffraction peaks at the following 2θ values and the corresponding relative intensity (RI) values which was given in parenthesis: 7.79 (100%), 15.58 (75.19%), 26.89 (11.73%), 27.08 (8.30%), and 31.41 (12.18%). Similarly, the ASP-II crystals (generated by using DEE) consisted of diffraction peaks at 7.94 (100%), 15.74 (81.17%), 26.93 (9.67%), 27.24 (11.04%), and 31.60 (9.62%), whereas the ASP-III (generated by using DCM) showed the diffraction peaks at 7.76 (31.74%), 15.63 (100%), 26.82 (4.27%), 27.12 (2.84%), and 31.41 (9.74%).…”

Section: Resultsmentioning

confidence: 99%

“…The ASP-I crystal showed a sharp diffraction peaks at the following 2θ values and the corresponding relative intensity (RI) values which was given in parenthesis: 7.79 (100%), 15.58 (75.19%), 26.89 (11.73%), 27.08 (8.30%), and 31.41 (12.18%). Similarly, the ASP-II crystals (generated by using DEE) consisted of diffraction peaks at 7.94 (100%), 15.74 (81.17%), 26.93 (9.67%), 27.24 (11.04%), and 31.60 (9.62%), whereas the ASP-III (generated by using DCM) showed the diffraction peaks at 7.76 (31.74%), 15.63 (100%), 26.82 (4.27%), 27.12 (2.84%), and 31.41 (9.74%). From the X-ray diffractograms, it appears that all the three drug crystals exhibited the diffraction peaks at an almost the same 2θ values with only minor variations.…”

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Studies on Aspirin Crystals Generated by a Modified Vapor Diffusion Method

et al. 2015

View full text Add to dashboard Cite

Abstract. The objectives of the current investigation were (1) to study the influence of selected two different non-solvents (diethylether and dichloromethane) on the drug crystal formation of a model drug, aspirin (ASP-I) by the modified vapor diffusion method and (2) to characterize and compare the generated crystals (ASP-II and ASP-III) using different analytical techniques with that of unprocessed ASP-I. When compared to the classical vapor diffusion method which consumes about 15 days to generate drug crystals, the modified method needs only 12 h to get the same. Fourier transform-infrared spectroscopy (FT-IR) reveals that the internal structures of ASP-II and ASP-III crystals were identical when compared with ASP-I. Although the drug crystals showed a close similarity in X-ray diffraction patterns, the difference in the relative intensities of some of the diffraction peaks (especially at 2θ values of around 7.7 and 15.5) could be attributed to the crystal habit or crystal size modification. Similarly, the differential scanning calorimetry (DSC) study speculates that only the crystal habit modifications might occur but without involving any change in internal structure of the generated drug polymorphic form I. This is further substantiated from the scanning electron microscopy (SEM) pictures that indicated the formation of platy shape for the ASP-II crystals and needle shape for the ASP-III crystals. In addition, the observed slow dissolution of ASP crystals should indicate polymorph form I formation. Thus, the modified vapor diffusion method could routinely be used to screen and legally secure all possible forms of other drug entities too.

show abstract

Polymorphic Crystal Forms and Cocrystals in Drug Delivery (Crystal Engineering)

Shan¹,

Zaworotko

2010

Burger's Medicinal Chemistry and Drug Discovery

View full text Add to dashboard Cite

Active pharmaceutical ingredients, APIs, are most conveniently developed and delivered orally as solid dosage forms that contain a defined crystalline form of an API. This means that the pharmacokinetic profile of a dosage form is at the very least linked to the physicochemical properties of the crystal form that is selected for development. Furthermore, that crystal forms of new chemical entities are novel, lack obviousness, and have utility makes them patentable. Therefore, selection of a specific crystal form for a given API is a profoundly important step in drug development from clinical, legal, and regulatory perspectives. In this context, scientific developments that afford greater understanding of and diversity in the number of crystalline forms available for a given API, which have traditionally been limited to salts, polymorphs, and hydrates/solvates [(a) Byrn SR, Pfeiffer RR, Stowell JG. Solid State Chemistry of Drugs. 2nd ed. West Lafayette, IN: SSCI, Inc.; 1999. (b) Haleblian JK. J. Pharm. Sci. 1975;64:1269–1288.], are obviously of relevance to the pharmaceutical industry. The science of crystal engineering [(a) Etter MC. J Phys Chem 1991;95:4601–4610. (b) Zerkowski JA, MacDonald JC, Seto CT, Wierda DA, Whitesides GM. J Am Chem Soc 1994;116:2382–2391. (c) Pepinsky R. Phys Rev 1955;100:971. (d) Schmidt GMJ. Pure Appl Chem 1971;27:647–678. (e) Desiraju GR. Crystal Engineering: The Design of Organic Solids. Amsterdam: Elsevier; 1989. (f) Moulton B, Zaworotko MJ. Chem Rev 2001;101: 1629–1658. (g) Braga D. Chem Commun 2003;22:2751–2754. (h) Hosseini MW. Coord Chem Rev 2003;240:157–166. (i) Desiraju GR. Angew Chem Int Ed Engl 1995;34: 2311–2327.] focuses upon self‐assembly of existing molecules or ions and it has evolved in such a manner that a wide range of new crystal forms can be generated without the need to invoke covalent‐bond breakage or formation. This contribution will address the impact of crystal engineering upon our fundamental understanding of crystal form diversity and how physical properties of crystals can be customized via the emerging class of crystal forms that have been termed pharmaceutical cocrystals [(a) Almarsson Ö, Zaworotko MJ. Chem Commun 2004; 1889–1896. (b) Vishweshwar P, McMahon JA, Bis JA, Zaworotko MJ. J Pharm Sci 2006;95:499–516. (c) Peterson ML, Hickey MB, Zaworotko MJ, Almarsson O. J Pharm Pharm Sci 2006;9:317–326. (d) Zaworotko M. Am Pharm Outsourc 2004;5: 16–23. (e) Shan N, Zaworotko MJ. Drug Discov Today 2008;13:440–446. (f) Blagden N, de Matas M, Gavan PT, Yoark P, Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates Adv Drug Del Rev 2007;59:617–630. (g) Nangia A. Cryst Growth Des 2008;8:1079–1081].

show abstract

The Predictably Elusive Form II of Aspirin

Abstract: The elusive form II of aspirin has been obtained during co-crystallization experiments with levetiracetam or acetamide, and it has been characterized by IR, DSC, HPLC, and single-crystal X-ray diffraction.

Cited by 326 publications

References 36 publications

Thermal properties of molecular crystals through dispersion-corrected quasi-harmonic ab initio calculations: the case of urea

Thermal properties of molecular crystals through dispersion-corrected quasi-harmonic ab initio calculations: the case of urea

Studies on Aspirin Crystals Generated by a Modified Vapor Diffusion Method

Polymorphic Crystal Forms and Cocrystals in Drug Delivery (Crystal Engineering)

Contact Info

Product

Resources

About