A Classification System to Assess the Crystallization Tendency of Organic Molecules from Undercooled Melts

Baird, Jared A.; Eerdenbrugh, Bernard Van; Taylor, Lynne S.

doi:10.1002/jps.22197

Cited by 571 publications

(733 citation statements)

References 70 publications

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“…Similar x-ray experiments on pure Probucol, Clofoctol, and Ketoprofen measured one week after laser heated containerless processing resulted in partial vitrification for levitated samples compared to the formation of fully crystalline forms cooled in containers. The melting and glass transition temperatures for the drugs melted in the levitator have been reported by Baird et al [15]. We note that in the cases of Ketoprofen, Clofoctol, Cinnazirine, and Miconazole Nitrate the glass transition temperature is less than room temperature and the samples were recovered and stored as supercooled liquids for a few days before x-ray characterization.…”

Section: B Vitrification By Laser Meltingsupporting

confidence: 67%

“…Similar containerless amorphization behavior is found here for Clotrimazole, Dibucaine, and Clofoctol. All of these molecules crystallize from ethanol solutions in containers but can form glasses by rapid quenching from the melt [15]. In at least two of the cases in this study, namely, Probucol and Ibuprofen, amorphous forms of the drugs have previously been produced by spray drying and mixing with a stabilizing agent.…”

Section: Fig 2 Insertmentioning

confidence: 99%

“…Of these drugs, Carbamazepine has been the most widely studied and differential scanning calorimetry measurements have reported difficulty in producing a purely amorphous form, even upon rapid quenching of the melt [15]. This is despite the fact that Carbamazepine has four crystalline polymorphs, all with similar molecular conformations and stabilities, and identical hydrogen bonding patterns [31].…”

Section: B Vitrification By Laser Meltingmentioning

confidence: 99%

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Amorphization of Molecular Liquids of Pharmaceutical Drugs by Acoustic Levitation

Benmore

Weber

2011

Phys. Rev. X

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It is demonstrated that acoustic levitation is able to produce amorphous forms from a variety of organic molecular compounds with different glass forming abilities. This can lead to enhanced solubility for pharmaceutical applications. High-energy x-ray experiments show that several viscous gels form from saturated pharmaceutical drug solutions after 10-20 min of levitation at room temperature, most of which can be frozen in solid form. Laser heating of ultrasonically levitated drugs can also result in the vitrification of molecular liquids, which is not attainable using conventional amorphization methods.

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Section: B Vitrification By Laser Meltingsupporting

confidence: 67%

Section: Fig 2 Insertmentioning

confidence: 99%

Section: B Vitrification By Laser Meltingmentioning

confidence: 99%

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Amorphization of Molecular Liquids of Pharmaceutical Drugs by Acoustic Levitation

Benmore

Weber

2011

Phys. Rev. X

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“…Melting of crystalline Td, which starts at 302.3 °C, indicates that the exotherm refers to sample crystallization. The occurrence of crystallization during heating of the amorphous sample places Td in the group II of the glass-forming drugs [2]. It is a requirement for the successful application of the current solubility method that a solid dispersion undergoes crystallization when annealed at a pre-set temperature.…”

Section: Physicochemical Analysis Of Tadalafil Solid Dispersionsmentioning

confidence: 99%

Physical stability of solid dispersions with respect to thermodynamic solubility of tadalafil in PVP-VA

Wlodarski

Sawicki

Kozyra

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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The aim of this paper was to evaluate physical stability of solid dispersions in respect to the drug, tadalafil (Td), in vinylpyrrolidone and vinyl acetate block copolymer (PVP-VA). Nine solid dispersions of Td in PVP-VA (Td/PVP-VA) varied in terms of quantitative composition (1:9-9:1, w/w) were successfully produced by spray-drying. Their amorphous nature, supersaturated character and molecular level of mixing (a solid solution structure) were subsequently confirmed using DSC, PXRD, SEM and calculation of Hansen total solubility parameters. Due to thermal degradation of both components before the melting point of Td

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“…Absence of the peaks in other heat-melt sugars and sugar alcohols indicated maintenance of the amorphous states. The crystallization profiles were categorized into three groups following a study by Baird et al 21) Class (I)-crystallized during cooling of the heat-melt, class (II)-crystallized during reheating of the heat-melt, and class (III)-no apparent crystallization in either during cooling or reheating scans. mesoErythritol and myo-inositol are categorized as Classes I and II since they showed crystallization peaks both during cooling of the heat-melt and reheating.…”

Section: Resultsmentioning

confidence: 99%

Physical Characterization of <i>meso</i>-Erythritol as a Crystalline Bulking Agent for Freeze-Dried Formulations

Fujii

Izutsu²,

Kume

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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The purpose of this study was to identify and characterize new crystalline bulking agents applicable to freeze-dried pharmaceuticals. Thermal analysis of heat-melt sugar and sugar alcohol solids as well as their frozen aqueous solutions showed high crystallization propensity of meso-erythritol and D-mannitol. Experimental freeze-drying of the aqueous meso-erythritol solutions after their cooling by two different methods (shelf-ramp cooling and immersion of vials into liquid nitrogen) resulted in cylindrical crystalline solids that varied in appearance and microscopic structure. Powder X-ray diffraction and thermal analysis indicated different crystallization processes of meso-erythritol depending on the extent of cooling. Cooling of the frozen meso-erythritol solutions at temperatures lower than their T g ′ (glass transition temperature of maximally freeze-concentrated phase, 59.7°C) induced a greater number of nuclei in the highly concentrated solute phase. Growth of multiple meso-erythritol anhydride crystals at around 40°C explains the powder-like fine surface texture of the solids dried after their immersion in liquid nitrogen. Contrarily, shelf-ramp cooling of the frozen solution down to 40°C induced an extensive growth of the solute crystal from a small number of nuclei, leading to scale-like patterns in the dried solids. An early transition of the freezing step into primary drying induced collapse of the non-crystalline region in the cakes. Appropriate process control should enable the use of meso-erythritol as an alternative crystalline bulking agent in freeze-dried formulations.Key words meso-erythritol; crystallization; freeze-drying; sugar alcohol; thermal analysis Freeze-drying is a popular method for formulating various therapeutic proteins, liposomes, and antibiotics that are not sufficiently stable during storage in aqueous solutions or during drying at high temperatures.1,2) The process is also used to prepare amorphous solid formulations that foster better dissolution rates and bioavailability of poorly soluble pharmaceuticals. Various active pharmaceutical ingredients (APIs) and excipients composing the freeze-dried solids are either in their amorphous or crystalline states.3) The component crystallinity is determined by various factors including their intrinsic properties, co-solute compositions, and thermal history of the process. 4)Many freeze-dried formulations contain amorphous or crystalline bulking agents to prevent loss of the APIs during handling and/or provide better appearance. Some disaccharides (e.g., sucrose and trehalose) form glass-state amorphous dried solids that protect the conformation of embedded proteins and supramolecular assembly of liposomes from dehydration-induced irreversible conformational changes during the process and from their chemical degradation during storage.5,6) Some excipients (e.g., D-mannitol and glycine) are used to obtain superior appearance of stable crystalline solids, although they do not show protein-stabilizing effects. 7) They crystallize mainly ...

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A Classification System to Assess the Crystallization Tendency of Organic Molecules from Undercooled Melts

Cited by 571 publications

References 70 publications

Amorphization of Molecular Liquids of Pharmaceutical Drugs by Acoustic Levitation

Amorphization of Molecular Liquids of Pharmaceutical Drugs by Acoustic Levitation

Physical stability of solid dispersions with respect to thermodynamic solubility of tadalafil in PVP-VA

Physical Characterization of <i>meso</i>-Erythritol as a Crystalline Bulking Agent for Freeze-Dried Formulations

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