Molecular Dynamics of the Cryomilled Base and Hydrochloride Ziprasidones by Means of Dielectric Spectroscopy

Kamiński, Kamil; Adrjanowicz, Karolina; Wojnarowska, Ż.; Grzybowska, K.; Hawełek, ᴌ.; Paluch, Marian; Żakowiecki, Daniel; Mazgalski, Jarosław

doi:10.1002/jps.22479

Cited by 30 publications

(33 citation statements)

References 53 publications

(92 reference statements)

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“…Since any of the above described methods do induce amorphization of cyclodextrins, another technique, i.e., ball milling in high-energy planetary mill was applied. In the literature there are many reports indicating that this technique can be used to transform crystalline materials into an amorphous one [30,31]. Moreover, it was demonstrated that in the case of poorly soluble and thermally unstable substances ball milling seems to be the only way of obtaining materials in the amorphous form.…”

Section: Resultsmentioning

confidence: 97%

Impact of water on molecular dynamics of amorphousα-,β-, andγ-cyclodextrins studied by dielectric spectroscopy

et al. 2012

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Dielectric, calorimetric, and x-ray diffraction measurements were carried out on α-, β-, and γ-cyclodextrins, which are cyclic saccharides built by, respectively, six, seven, and eight glucose units connected via glycosidic linkage. Differential scanning calorimetry measurements indicated that each carbohydrate has a melting temperature located much above the temperature at which thermal decomposition begins. Moreover, calorimetric data revealed that it is possible to completely dehydrate each cyclodextrin by annealing them above 413 K. Unfortunately, it is impossible to obtain amorphous forms of cyclodextrin by simple cooling of the melt. Thus, a solid state amorphization method has been applied. X-ray diffraction studies demonstrated that by ball milling at room temperature we are able to obtain completely amorphous cyclodextrins. Finally, dielectric measurements were carried out to probe molecular dynamics in the amorphous state of cyclodextrins. It was found that there is only one relaxation process in amorphous hydrated cyclodextrins, while in dried samples two secondary relaxations are present. Moreover, we have shown that water has an enormous effect on the dynamics of both relaxation modes, i.e., with increasing content of water, the activation energy of the slow mode decreases, while that evaluated for the fast mode increases. We were not able to follow the dynamics of the structural relaxation process, because glass transition temperatures of amorphous cyclodextrins were found to lie above thermal degradation points.

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Section: Resultsmentioning

confidence: 97%

Impact of water on molecular dynamics of amorphousα-,β-, andγ-cyclodextrins studied by dielectric spectroscopy

et al. 2012

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“…For this reason, there has been a great deal of interest for the pharmaceutical industry in making amorphous pharmaceuticals and others to study their physical properties. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Often the pharmaceuticals have chemical bonds and structures that are not common to the glass-formers studied in the physics or chemistry laboratories. Thus, extraordinary molecular dynamics and physical properties may be expected from the study of the glass-forming pharmaceuticals.…”

Section: Introductionmentioning

confidence: 98%

Fundamentals of ionic conductivity relaxation gained from study of procaine hydrochloride and procainamide hydrochloride at ambient and elevated pressure

Wojnarowska¹,

Swiety-Pospiech²,

Grzybowska³

et al. 2012

The Journal of Chemical Physics

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The pharmaceuticals, procaine hydrochloride and procainamide hydrochloride, are glass-forming as well as ionically conducting materials. We have made dielectric measurements at ambient and elevated pressures to characterize the dynamics of the ion conductivity relaxation in these pharmaceuticals, and calorimetric measurements for the structural relaxation. Perhaps due to their special chemical and physical structures, novel features are found in the ionic conductivity relaxation of these pharmaceuticals. Data of conductivity relaxation in most ionic conductors when represented by the electric loss modulus usually show a single resolved peak in the electric modulus loss M(")(f) spectra. However, in procaine hydrochloride and procainamide hydrochloride we find in addition another resolved loss peak at higher frequencies over a temperature range spanning across T(g). The situation is analogous to many non-ionic glass-formers showing the presence of the structural α-relaxation together with the Johari-Goldstein (JG) β-relaxation. Naturally the analogy leads us to name the slower and faster processes resolved in procaine hydrochloride and procainamide hydrochloride as the primary α-conductivity relaxation and the secondary β-conductivity relaxation, respectively. The analogy of the β-conductivity relaxation in procaine HCl and procainamide HCl with JG β-relaxation in non-ionic glass-formers goes further by the finding that the β-conductivity is strongly related to the α-conductivity relaxation at temperatures above and below T(g). At elevated pressure but compensated by raising temperature to maintain α-conductivity relaxation time constant, the data show invariance of the ratio between the β- and the α-conductivity relaxation times to changes of thermodynamic condition. This property indicates that the β-conductivity relaxation has fundamental importance and is indispensable as the precursor of the α-conductivity relaxation, analogous to the relation found between the Johari-Goldstein β-relaxation and the structural α-relaxation in non-ionic glass-forming systems. The novel features of the ionic conductivity relaxation are brought out by presenting the measurements in terms of the electric modulus or permittivity. If presented in terms of conductivity, the novel features are lost. This warns against insisting that a log-log plot of conductivity vs. frequency is optimal to reveal and interpret the dynamics of ionic conductors.

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“…Another, an alternative way is preparing the amorphous form of those compounds. Recently, it has been often reported that pharmaceuticals prepared in the amorphous form are significantly more soluble, have higher dissolution rate, and have greater bioavailability than their crystalline counterparts 4,5,6 .…”

Section: Introductionmentioning

confidence: 99%

Molecular Dynamics and Physical Stability of Amorphous Nimesulide Drug and Its Binary Drug–Polymer Systems

et al. 2016

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In this paper we study the effectiveness of three well known polymers: inulin, Soluplus and PVP in stabilizing amorphous form of nimesulide (NMS) drug. The recrystallization tendency of pure drug as well as measured drug-polymer systems were examined at isothermal conditions by using broadband dielectric spectroscopy (BDS), and at non-isothermal conditions by differential scanning calorimetry (DSC). Our investigation has shown that the crystallization half-life time of pure NMS at 328 K is equal to 33 minutes. We found that this time can be prolonged to 40 years after adding to NMS 20% of PVP polymer.This polymer proved to be the best NMS's stabilizer, while the worst stabilization effect was found after adding the inulin to NMS. Additionally, our DSC, BDS and FTIR studies indicate that for suppression of NMS's re-crystallization in NMS-PVP system, the two mechanisms are responsible: the polymeric steric hindrances as well as the antiplastization effect excerted by the excipient.

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Molecular Dynamics of the Cryomilled Base and Hydrochloride Ziprasidones by Means of Dielectric Spectroscopy

Cited by 30 publications

References 53 publications

Impact of water on molecular dynamics of amorphousα-,β-, andγ-cyclodextrins studied by dielectric spectroscopy

Impact of water on molecular dynamics of amorphousα-,β-, andγ-cyclodextrins studied by dielectric spectroscopy

Fundamentals of ionic conductivity relaxation gained from study of procaine hydrochloride and procainamide hydrochloride at ambient and elevated pressure

Molecular Dynamics and Physical Stability of Amorphous Nimesulide Drug and Its Binary Drug–Polymer Systems

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