Compression-Induced Crystallization in Sucrose-Polyvinylpyrrolidone Amorphous Solid Dispersions

Bērziņš, Kārlis; Suryanarayanan, Raj

doi:10.1021/acs.cgd.7b01305

Cited by 25 publications

(8 citation statements)

References 26 publications

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“…8 On the other hand, compression of amorphous drugs such as indomethacin, sucrose, celecoxib caused its crystallization. [9][10][11] Crystallization was most pronounced on the radial tablet surface, which comes in contact with die wall and was attributed to die wall friction. 10 There are also several examples of compression-induced crystalline / crystalline (i.e., polymorphic) transformations.…”

Section: Introductionmentioning

confidence: 99%

Compression-Induced Polymorphic Transformation in Tablets: Role of Shear Stress and Development of Mitigation Strategies

Thakral

Stephenson

et al. 2019

Journal of Pharmaceutical Sciences

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a b s t r a c tOur goals were to evaluate the effects of (i) hydrostatic pressure alone and (ii) its combined effect with shear stress during compaction, on the polymorphic transformation (form C / A) of a model drug, chlorpropamide. The powder was either subjected to hydrostatic pressure in a pressure vessel or compressed in a tablet press, at pressures ranging from 25 to 150 MPa. The overall extent of phase transformation was determined by powder X-ray diffractometry, whereas 2D-X-ray diffractometry enabled quantification of the spatial distribution of phase composition in tablets. Irrespective of the pressure, the extent of transformation following compaction was higher than that because of hydrostatic pressure alone, the difference attributed to the contribution of shear stress experienced during compaction. At a compression pressure of 25 MPa, there was a pronounced gradient in the extent of phase transformation when monitored from radial tablet surface to core. This gradient decreased with increase in compression pressure. Four approaches were attempted to minimize the effect of compression-induced phase transformation: (a) site-specific lubrication, (b) use of a viscoelastic excipient, (c) ceramic-lined die, and (d) use of cavity tablet. The ceramic-lined die coupled with site-specific lubrication was most effective in minimizing the extent of compression-induced phase transformation.

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Section: Introductionmentioning

confidence: 99%

Compression-Induced Polymorphic Transformation in Tablets: Role of Shear Stress and Development of Mitigation Strategies

Thakral

Stephenson

et al. 2019

Journal of Pharmaceutical Sciences

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“…Applying mechanical forces, such as compression, may induce phase separation and nucleation and hence facilitate the recrystallization of the co-amorphous tablets, namely, “compression-induced crystallization” [ 36 ]. In order to investigate whether this phenomenon occurred in the current systems, a tablet from each formulation was gently crushed with a pestle.…”

Section: Resultsmentioning

confidence: 99%

Compaction Behavior of Co-Amorphous Systems

2023

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Co-amorphous systems have been shown to be a promising strategy to address the poor water solubility of many drug candidates. However, little is known about the effect of downstream processing-induced stress on these systems. The aim of this study is to investigate the compaction properties of co-amorphous materials and their solid-state stability upon compaction. Model systems of co-amorphous materials consisting of carvedilol and the two co-formers aspartic acid and tryptophan were produced via spray drying. The solid state of matter was characterized using XRPD, DSC, and SEM. Co-amorphous tablets were produced with a compaction simulator, using varying amounts of MCC in the range of 24 to 95.5% (w/w) as a filler, and showed high compressibility. Higher contents of co-amorphous material led to an increase in the disintegration time; however, the tensile strength remained rather constant at around 3.8 MPa. No indication of recrystallization of the co-amorphous systems was observed. This study found that co-amorphous systems are able to deform plastically under pressure and form mechanically stable tablets.

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“…In granulation of formulation, ∆H i is defined as quotient of the melting enthalpy of the sample determined by DSC analysis to the FXD content (%, w/w) of FXDexcipients formulation. In other words, the enthalpy ∆H i value has been normalized for the FXD content in formulation [18,19]. The quantification of Form I content % can be used to reflect the phase transformation of FXD during wet granulation process.…”

Section: Data Analysis Of the Degree Of Phase Transformation Of Fxdmentioning

confidence: 99%

Solid Form and Phase Transformation Properties of Fexofenadine Hydrochloride during Wet Granulation Process

Zhao

et al. 2021

Pharmaceutics

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The quality control of drug products during manufacturing processes is important, particularly the presence of different polymorphic forms in active pharmaceutical ingredients (APIs) during production, which could affect the performance of the formulated products. The objective of this study was to investigate the phase transformation of fexofenadine hydrochloride (FXD) and its influence on the quality and performance of the drug. Water addition was key controlling factor for the polymorphic conversion from Form I to Form II (hydrate) during the wet granulation process of FXD. Water-induced phase transformation of FXD was studied and quantified with XRD and thermal analysis. When FXD was mixed with water, it rapidly converted to Form II, while the conversion is retarded when FXD is formulated with excipients. In addition, the conversion was totally inhibited when the water content was <15% w/w. The relationship between phase transformation and water content was studied at the small scale, and it was also applicable for the scale-up during wet granulation. The effect of phase transition on the FXD tablet performance was investigated by evaluating granule characterization and dissolution behavior. It was shown that, during the transition, the dissolved FXD acted as a binder to improve the properties of granules, such as density and flowability. However, if the water was over added, it can lead to the incomplete release of the FXD during dissolution. In order to balance the quality attributes and the dissolution of granules, the phase transition of FXD and the water amount added should be controlled during wet granulation.

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Compression-Induced Crystallization in Sucrose-Polyvinylpyrrolidone Amorphous Solid Dispersions

Cited by 25 publications

References 26 publications

Compression-Induced Polymorphic Transformation in Tablets: Role of Shear Stress and Development of Mitigation Strategies

Compression-Induced Polymorphic Transformation in Tablets: Role of Shear Stress and Development of Mitigation Strategies

Compaction Behavior of Co-Amorphous Systems

Solid Form and Phase Transformation Properties of Fexofenadine Hydrochloride during Wet Granulation Process

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