Dissolution enhancement of Deflazacort using hollow crystals prepared by antisolvent crystallization process

Paulino, Amarilis Scremin; Rauber, Gabriela Schneider; Campos, Carlos Eduardo Maduro de; Maurício, M. H. P.; Avillez, Roberto R. de; Capobianco, G.; Cardoso, Simone Gonçalves; Cuffini, Silvia Lucía

doi:10.1016/j.ejps.2013.03.014

Cited by 21 publications

(15 citation statements)

References 33 publications

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“…Salicylic acid (SA), the compound of focus in this study, was similarly reported in 2006 to crystallize with hollow voids in the center, which was also investigated by Seidel and Ulrich, 2015 and Tierney et al , 2017 . Many other examples are now known covering a wide spectrum of organic compounds, − which speaks to the generality of this intriguing morphology and the many potential applications in the pharmaceutical industry and elsewhere.…”

Section: Introductionmentioning

confidence: 52%

Formation of Macrotubular Crystals of Salicylic Acid through Ripening of Solid Solution Crystals Containing Impurity Gradients

Wang

Raikes

et al. 2021

Crystal Growth & Design

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We report a ripening mechanism in crystallization of an organic compound that is observable above 1 μm and is different from Ostwald ripening. Salicylic acid crystallized in methanol and water in the presence of simulated structurally similar impurities resulted in impurity entrapment via the formation of solid solutions. Impurities were retained in the solids to a higher degree in the early part of the crystallization and decreased rapidly toward the end. This uneven impurity entrapment resulted in impurity gradients in individual crystals, which were detected and confirmed by Raman imaging. The impurity entrapment impacted the physical properties of salicylic acid, including its solubility and melting properties. An intra-particle thermodynamic driving force was thus found to exist during the crystallization, which caused selective dissolution of the dirtier cores of the crystal and recrystallization on the cleaner edges. These concomitant but opposing mass transfer processes during the crystallization were responsible for the formation of hollow crystals of salicylic acid. The ripening phenomenon is demonstrated experimentally in the beginning and end of an isothermal anti-solvent crystallization as well as during an agitated filter dryer operation.

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Section: Introductionmentioning

confidence: 52%

Formation of Macrotubular Crystals of Salicylic Acid through Ripening of Solid Solution Crystals Containing Impurity Gradients

Wang

Raikes

et al. 2021

Crystal Growth & Design

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“…The higher frequency/uniformity of the hollowing effect, and the deeper indentations observed at higher supersaturation (Figure b), may be explained by an increase in supersaturation-induced crystal defects. Some examples of hollow crystals formed via dissolution–recrystallization, − melt/sublimation–recrystallization, , or variations of these mechanisms have been reported in the literature.…”

Section: Discussionmentioning

confidence: 99%

Size and Shape Control of Micron-Sized Salicylic Acid Crystals during Antisolvent Crystallization

Tierney

Rasmuson

Hudson

2017

Org. Process Res. Dev.

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During an antisolvent crystallization process, micron-sized crystals of salicylic acid in the particle size range 20 to 150 μm were prepared under specific sets of crystallization conditions, with a focus on drug concentration, temperature, and solvent composition. For each experiment, the size outcome was determined by a number of knock on (often competing) influencing factors, including supersaturation, mass available for deposition during crystallization, and influence of temperature and solvent composition on crystallization kinetics. A certain fraction of the crystals, especially at higher solute concentration, developed a spectacular hollow shape with an almost perfect rectangular outer cross-section. A mechanistic explanation for the formation of hollow crystals is proposed. The use of additives during crystallization introduced further control over the size and, perhaps more noticeably, over the shape of the salicylic acid crystals. The lengths of salicylic acid crystals decreased to as low as 6 μm with increasing concentration of HPMC. Both HPMC and CMC induced a change in the crystal habit from square prisms (for the pure system) to needles, due to the structural ability of these additives to selectively attach through hydrogen bonding to the dominating 110 faces of the crystals and slow down growth in that direction. SDS exhibited less of an influence on the size, but due to its attachment to the 001 faces, it prevented indentation of these faces from occurring and thus prevented the formation of hollow crystals.

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“…Poorly soluble molecules have been successfully formulated by employing a variety of techniques to modify the physico-chemical and biopharmaceutical properties of drugs [3,4] such as: (i) solubilization in surfactant solutions; (ii) use of co-solvents [5], salt formation [6], complexation with cyclodextrins [7], crystallization [8], amorphization [9], milling [10], etc.…”

Section: Introductionmentioning

confidence: 99%

The Effect of an Optimized Wet Milling Technology on the Crystallinity, Morphology and Dissolution Properties of Micro- and Nanonized Meloxicam

et al. 2016

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This article reports on the effects of a new combined wet milling technique on the physicochemical properties of meloxicam (MEL). The influence of milling time on the particle size, the crystallinity, the morphology and the dissolution rate of MEL has been studied in the presence and absence of polyvinyl alcohol (PVA) as a stabilizer agent. Micronized MEL particles were produced in aqueous medium which did not contain additive after milling for 10 min. For nanonization an additive and longer milling time were required. After particle size determination the structural and morphological characterization of the wet milled, dried products containing MEL were studied. X-ray powder diffractometry (XRPD) and differential scanning calorimetry (DSC) examinations revealed the change in the crystallinity of MEL. Scanning electron microscopy (SEM) images showed that aggregates of nanosized MEL particles were formed, regardless of the presence of PVA. The nanonized MEL crystals (D 50 = 126 nm) exhibited a regular shape and a smooth surface. The increased specific surface area resulted in a high dissolution rate and concentration of free MEL. According to the results, the produced samples could be applied as a basic material (micronized MEL) and intermediate product (micronized and nanonized MEL with PVA) for the design of dosage forms.

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Dissolution enhancement of Deflazacort using hollow crystals prepared by antisolvent crystallization process

Cited by 21 publications

References 33 publications

Formation of Macrotubular Crystals of Salicylic Acid through Ripening of Solid Solution Crystals Containing Impurity Gradients

Formation of Macrotubular Crystals of Salicylic Acid through Ripening of Solid Solution Crystals Containing Impurity Gradients

Size and Shape Control of Micron-Sized Salicylic Acid Crystals during Antisolvent Crystallization

The Effect of an Optimized Wet Milling Technology on the Crystallinity, Morphology and Dissolution Properties of Micro- and Nanonized Meloxicam

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