Polymorphic Transformation of Indomethacin Under High Pressures**The previous affiliation when this study was done, Organic Synthesis Research Laboratory, Sumitomo Chemical Co., Ltd. 3-1-98, Kasugade-naka, Konohana-ku, Osaka 554-8558, Japan.

Okumura, Tsuyoshi; Ishida, Masaya; Takayama, K.; Otsuka, Makoto

doi:10.1002/jps.20557

Cited by 55 publications

(14 citation statements)

References 44 publications

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“…Yoshioka et al have demonstrated that by varying the cooling rate one can obtain predominantly α-form (fast cooling) or γ-form (slow cooling) . However, on increased pressure, the α-form of indomethacin is expected to be thermodynamically more favorable . This we have also observed for our samples crystallized under compression.…”

Section: Methodssupporting

confidence: 74%

“…The studied sample is indomethacin, a model glass-forming substance showing crystallization tendencies above and below the glass transition. The crystallization behavior of indomethacin has been intensively investigated at atmospheric pressure − and partially at elevated pressure (even by some of us when introducing the isochronal crystallization approach). ,− Now, we have enriched this knowledge by identifying in the phase diagram of the supercooled indomethacin various iso-invariant lines and determine their position regarding each other and the maxima of the nucleation and growth rate curves. Obtained results provide new insight into the fundamental aspects of the crystallization phenomenon by taking a full advantage of using different combinations of the temperature and pressure.…”

Section: Introductionmentioning

confidence: 99%

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Exploring the Crystallization Tendency of Glass-Forming Liquid Indomethacin in the T–p Plane by Finding Different Iso-Invariant Points

Adrjanowicz

Koperwas

Szklarz

et al. 2016

Crystal Growth & Design

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In this work, we examine in detail the crystallization tendency of the model glass-forming liquid indomethacin at varying thermodynamic conditions. To do that, we combine experimental results with predictions of the classical theories of nucleation and growth. We have considered changes in the crystallization rate k along iso-invariant curves located differently in the T–p phase diagram of the studied supercooled liquid. We include for the first time temperature and pressure conditions along which the thermodynamic driving force toward crystallization, commonly discussed as the difference in the chemical potential of the liquid/crystalline phases, Δμ, is expected to remain constant. Although the increase in pressure fosters crystallization (due to an increasing overlap of the nucleation and growth rates maxima), we show that when moving along certain thermodynamic paths the crystallization rate remains unchanged, or it is only slightly affected by the density increase. Therefore, by studying the kinetics of crystallization in the T–p phase space, we were able to provide information on the vast importance to get a better understanding of the crystallization behavior of the glass-forming materials and methods that can be used to tune this process.

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Section: Methodssupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Exploring the Crystallization Tendency of Glass-Forming Liquid Indomethacin in the T–p Plane by Finding Different Iso-Invariant Points

Adrjanowicz

Koperwas

Szklarz

et al. 2016

Crystal Growth & Design

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“…In the tablets API can be exposed to a considerable range of temperature and humidity, , which can trigger further transformations . The effects of high pressure on the crystals of organic compounds, − as well as technologically important mechanochemical and tableting effects, have been studied . High-pressure investigations relevant to the pharmaceutical compounds include three main aspects: (i) pressure-induced solid phase transitions; − (ii) high pressure effect on the crystal structure; ,, and (iii) synthesis of new polymorphs and solvates at high pressure. , …”

Section: Introductionmentioning

confidence: 99%

Pressure-Stabilized Solvates of Xylazine Hydrochloride

Olejniczak

Krūkle-Bērziņa

Katrusiak

2016

Crystal Growth & Design

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High pressure strongly favors the highest-density polymorph Z of active pharmaceutical ingredient 2-(2,6-xylidino)-5,6-dihydro-4H-1,3-thiazine hydrochloride (xylazine hydrochloride, XylHCl) up to about 0.1 GPa only, but still higher pressure destabilizes this structure. Above 0.1 GPa, XylHCl preferentially crystallizes as solvates with CH2Cl2, CHCl3, or (CH3)2CHOH depending on the solvent used. However, when XylHCl·H2O is dissolved in any of these solvents, the high-pressure crystallizations yield the hydrate XylHCl·H2O only. The single crystals of the CH2Cl2, CHCl3, and (CH3)2CHOH solvates could be grown in situ in a diamond anvil cell, which allowed their structure determination from the single-crystal diffraction data. At 0.4 GPa the XylHCl·H2O hydrate undergoes a pressure-induced phase transition doubling the unit cell dimensions.

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“…It can be seen that IND can be converted into its amorphous form upon ball milling, either as a pure drug or as a glass solution with PVP. As reported previously, the presence of an amorphous form is indicated by the absence of diffraction peaks and the appearance of a halo pattern [ 24 , 25 , 26 ].…”

Section: Resultsmentioning

confidence: 66%

The Influence of Pressure on the Intrinsic Dissolution Rate of Amorphous Indomethacin

et al. 2014

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New drug candidates increasingly tend to be poorly water soluble. One approach to increase their solubility is to convert the crystalline form of a drug into the amorphous form. Intrinsic dissolution testing is an efficient standard method to determine the intrinsic dissolution rate (IDR) of a drug and to test the potential dissolution advantage of the amorphous form. However, neither the United States Pharmacopeia (USP) nor the European Pharmacopeia (Ph.Eur) state specific limitations for the compression pressure in order to obtain compacts for the IDR determination. In this study, the influence of different compression pressures on the IDR was determined from powder compacts of amorphous (ball-milling) indomethacin (IND), a glass solution of IND and poly(vinylpyrrolidone) (PVP) and crystalline IND. Solid state properties were analyzed with X-ray powder diffraction (XRPD) and the final compacts were visually observed to study the effects of compaction pressure on their surface properties. It was found that there is no significant correlation between IDR and compression pressure for crystalline IND and IND–PVP. This was in line with the observation of similar surface properties of the compacts. However, compression pressure had an impact on the IDR of pure amorphous IND compacts. Above a critical compression pressure, amorphous particles sintered to form a single compact with dissolution properties similar to quench-cooled disc and crystalline IND compacts. In such a case, the apparent dissolution advantage of the amorphous form might be underestimated. It is thus suggested that for a reasonable interpretation of the IDR, surface properties of the different analyzed samples should be investigated and for amorphous samples the IDR should be measured also as a function of the compression pressure used to prepare the solid sample for IDR testing.

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Polymorphic Transformation of Indomethacin Under High Pressures**The previous affiliation when this study was done, Organic Synthesis Research Laboratory, Sumitomo Chemical Co., Ltd. 3-1-98, Kasugade-naka, Konohana-ku, Osaka 554-8558, Japan.

Cited by 55 publications

References 44 publications

Exploring the Crystallization Tendency of Glass-Forming Liquid Indomethacin in the T–p Plane by Finding Different Iso-Invariant Points

Exploring the Crystallization Tendency of Glass-Forming Liquid Indomethacin in the T–p Plane by Finding Different Iso-Invariant Points

Pressure-Stabilized Solvates of Xylazine Hydrochloride

The Influence of Pressure on the Intrinsic Dissolution Rate of Amorphous Indomethacin

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