Effect of temperature and moisture on the miscibility of amorphous dispersions of felodipine and poly(vinyl pyrrolidone)

Marsac, Patrick J.; Rumondor, Alfred C. F.; Nivens, David E.; Kestur, Umesh S.; Stanciu, Lia; Taylor, Lynne S.

doi:10.1002/jps.21809

Cited by 176 publications

(201 citation statements)

References 47 publications

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“…9). However, similar to other model APIs with NH-type hydrogen-bond donors (5,7), this system exhibits moisture-induced amorphous-amorphous phase separation with PVP at all drug-polymer ratios investigated. These observations highlight the complexity of this phenomenon and the need to consider not only drug and polymer properties, but also the relative proportions of each component.…”

Section: Discussionsupporting

confidence: 66%

“…One factor in particular, the absorption of moisture, has been shown to accelerate crystallization of amorphous APIs in pure form as well as when mixed with other ingredients (2)(3)(4). For binary systems, it has been demonstrated that the absorption of moisture can lead to the formation of regions with different API-polymer concentrations from the corresponding one-phase amorphous system (where the API and the polymer were originally mixed at the molecular level) (5). Here, the absorption of moisture induces amorphous-amorphous phase separation.…”

Section: Introductionmentioning

confidence: 99%

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Understanding the Tendency of Amorphous Solid Dispersions to Undergo Amorphous–Amorphous Phase Separation in the Presence of Absorbed Moisture

et al. 2011

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Abstract. Formulation of an amorphous solid dispersion (ASD) is one of the methods commonly considered to increase the bioavailability of a poorly water-soluble small-molecule active pharmaceutical ingredient (API). However, many factors have to be considered in designing an API-polymer system, including any potential changes to the physical stability of the API. In this study, the tendency of ASD systems containing a poorly water-soluble API and a polymer to undergo amorphous-amorphous phase separation was evaluated following exposure to moisture at increasing relative humidity. Infrared spectroscopy was used as the primary method to investigate the phase behavior of the systems. In general, it was observed that stronger drug-polymer interactions, low-ASD hygroscopicity, and a less hydrophobic API led to the formation of systems resistant to moisture-induced amorphous-amorphous phase separation. Orthogonal partial least squares analysis provided further insight into the systems, confirming the importance of the aforementioned properties. In order to design a more physically stable ASD that is resistant to moisture-induced amorphous-amorphous phase separation, it is important to consider the interplay between these properties.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Understanding the Tendency of Amorphous Solid Dispersions to Undergo Amorphous–Amorphous Phase Separation in the Presence of Absorbed Moisture

et al. 2011

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“…The crystallization process appeared to occur during vapor absorption in the RH range of 55-60% RH, as evident by the sharp decrease in water vapor uptake over a narrow RH range followed by the plateau in vapor uptake. It is generally recognized that temperature and RH are two important factors on the phase transition behavior and stability on amorphous phases (39,40). As expected for crystalline hydrate powders, raw trehalose dihydrate did not absorb any significant amounts of water vapor over the entire range of RH, as it is in its thermodynamically stable state.…”

Section: Discussionmentioning

confidence: 63%

Physicochemical Characterization and Water Vapor Sorption of Organic Solution Advanced Spray-Dried Inhalable Trehalose Microparticles and Nanoparticles for Targeted Dry Powder Pulmonary Inhalation Delivery

Mansour

2011

AAPS PharmSciTech

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Abstract. Novel advanced spray-dried inhalable trehalose microparticulate/nanoparticulate powders with low water content were successfully produced by organic solution advanced spray drying from dilute solution under various spray-drying conditions. Laser diffraction was used to determine the volumetric particle size and size distribution. Particle morphology and surface morphology was imaged and examined by scanning electron microscopy. Hot-stage microscopy was used to visualize the presence/absence of birefringency before and following particle engineering design pharmaceutical processing, as well as phase transition behavior upon heating. Water content in the solid state was quantified by Karl Fisher (KF) coulometric titration. Solidstate phase transitions and degree of molecular order were examined by differential scanning calorimetry (DSC) and powder X-ray diffraction, respectively. Scanning electron microscopy showed a correlation between particle morphology, surface morphology, and spray drying pump rate. All advanced spray-dried microparticulate/nanoparticulate trehalose powders were in the respirable size range and exhibited a unimodal distribution. All spray-dried powders had very low water content, as quantified by KF. The absence of crystallinity in spray-dried particles was reflected in the powder X-ray diffractograms and confirmed by thermal analysis. DSC thermal analysis indicated that the novel advanced spray-dried inhalable trehalose microparticles and nanoparticles exhibited a clear glass transition (T g ). This is consistent with the formation of the amorphous glassy state. Spray-dried amorphous glassy trehalose inhalable microparticles and nanoparticles exhibited vapor-induced (lyotropic) phase transitions with varying levels of relative humidity as measured by gravimetric vapor sorption at 25°C and 37°C.

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“…(7) What is the effect of moisture on the stability of amorphous drugs and formulations? (15) We will focus this review on crystal growth in organic glasses. We do so because of recent progress in this area and because crystal growth in organic glasses has properties unknown for (and thus unpredictable from the behaviors of) other materials.…”

Section: Introductionmentioning

confidence: 99%

Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives

Sun

Zhu

et al. 2012

AAPS J

136

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Abstract. We review recent progress toward understanding and enhancing the stability of amorphous pharmaceutical solids against crystallization. As organic liquids are cooled to become glasses, fast modes of crystal growth can emerge. One such growth mode, the glass-to-crystal or GC mode, occurs in the bulk, and another exists at the free surface, both leading to crystal growth much faster than predicted by theories that assume diffusion defines the kinetic barrier of crystallization. These phenomena have received different explanations, and we propose that GC growth is a solid-state transformation enabled by local mobility in glasses and that fast surface crystal growth is facilitated by surface molecular mobility. In the second part, we review recent findings concerning the effect of polymer additives on crystallization in organic glasses. Low-concentration polymer additives can strongly inhibit crystal growth in the bulk of organic glasses, while having weaker effect on surface crystal growth. Ultra-thin polymer coatings can inhibit surface crystallization. Recent work has shown the importance of molecular weight for crystallization inhibitors of organic glasses, besides "direct intermolecular interactions" such as hydrogen bonding. Relative to polyvinylpyrrolidone, the VP dimer is far less effective in inhibiting crystal growth in amorphous nifedipine. Further work is suggested for better understanding of crystallization of amorphous organic solids and the prediction of their stability.

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Effect of temperature and moisture on the miscibility of amorphous dispersions of felodipine and poly(vinyl pyrrolidone)

Cited by 176 publications

References 47 publications

Understanding the Tendency of Amorphous Solid Dispersions to Undergo Amorphous–Amorphous Phase Separation in the Presence of Absorbed Moisture

Understanding the Tendency of Amorphous Solid Dispersions to Undergo Amorphous–Amorphous Phase Separation in the Presence of Absorbed Moisture

Physicochemical Characterization and Water Vapor Sorption of Organic Solution Advanced Spray-Dried Inhalable Trehalose Microparticles and Nanoparticles for Targeted Dry Powder Pulmonary Inhalation Delivery

Stability of Amorphous Pharmaceutical Solids: Crystal Growth Mechanisms and Effect of Polymer Additives

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