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Artikel: Chronic pulmonary aspergillosis in a tertiary tuberculosis institute: A common entity missed commonly.

Singhal, Ritu / Gupta, Amitesh / Singla, Neeta / Singla, Rupak / Jha, Ritika / Raina, Shweta / Choudhary, Madhumita Paul / Bhattacherjee, Nilotpal

The Indian journal of tuberculosis

2023 Band 70, Heft 3, Seite(n) 276–285

Abstract: The disease chronic pulmonary aspergillosis (CPA), which has 3 million cases globally, has a substantial impact on global health. The morbidity and mortality it cause are also rather severe. Patients with modest immune suppression or those with ... ...

Abstract	The disease chronic pulmonary aspergillosis (CPA), which has 3 million cases globally, has a substantial impact on global health. The morbidity and mortality it cause are also rather severe. Patients with modest immune suppression or those with underlying structural and chronic lung illnesses are more likely to develop this condition. CPA pose a diagnostic and management challenge to clinicians. The condition causes patients to have persistent respiratory difficulties, which lowers their quality of life, and the therapy is lengthy and offers few choices. Particularly in a nation like India, where tuberculosis (TB) is prevalent and patients exhibit identical signs and symptoms, a strong index of suspicion is required. Treated pulmonary TB patients, presenting with symptoms or chest x-ray abnormalities, especially those with presence of cavity are also more prone to develop CPA. The constellation of symptoms together with presence of microbiological criteria and suggestive radiology can help to reach at the diagnosis. The field of mycology has made major developments, but there is still much to understand about this illness and to establish timely diagnoses and make the best use of the existing treatment choices. The burden of CPA in patients with treated TB is highlighted in this article along with the most recent research and clinical guidelines.
Mesh-Begriff(e)	Humans ; Quality of Life ; Pulmonary Aspergillosis/complications ; Pulmonary Aspergillosis/diagnosis ; Lung ; Tuberculosis ; Tuberculosis, Pulmonary/complications ; Tuberculosis, Pulmonary/diagnosis ; Tuberculosis, Pulmonary/drug therapy ; Chronic Disease
Sprache	Englisch
Erscheinungsdatum	2023-04-01
Erscheinungsland	India
Dokumenttyp	Journal Article ; Review
ZDB-ID	603129-8
ISSN	0019-5707 ; 0019-5705
ISSN	0019-5707 ; 0019-5705
DOI	10.1016/j.ijtb.2023.03.014
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Crystallization from Supersaturated Solutions: Role of Lecithin and Composite Simulated Intestinal Fluid.

Indulkar, Anura S / Gao, Yi / Raina, Shweta A / Zhang, Geoff G Z / Taylor, Lynne S

Pharmaceutical research

2018 Band 35, Heft 8, Seite(n) 158

Abstract: Purpose: The overall purpose of this study was to understand the impact of different biorelevant media types on solubility and crystallization from supersaturated solutions of model compounds (atazanavir, ritonavir, tacrolimus and cilnidipine). The ... ...

Abstract	Purpose: The overall purpose of this study was to understand the impact of different biorelevant media types on solubility and crystallization from supersaturated solutions of model compounds (atazanavir, ritonavir, tacrolimus and cilnidipine). The first aim was to understand the influence of the lecithin content in FaSSIF. As the human intestinal fluids (HIFs) contain a variety of bile salts in addition to sodium taurocholate (STC), the second aim was to understand the role of these bile salts (in the presence of lecithin) on solubility and crystallization from supersaturated solutions, METHODS: To study the impact of lecithin, media with 3 mM STC concentration but varying lecithin concentration were prepared. To test the impact of different bile salts, a new biorelevant medium (Composite-SIF) with a composition simulating that found in the fasted HIF was prepared. The crystalline and amorphous solubility was determined in these media. Diffusive flux measurements were performed to determine the true supersaturation ratio at the amorphous solubility of the compounds in various media. Nucleation induction times from supersaturated solutions were measured at an initial concentration equal to the amorphous solubility (equivalent supersaturation) of the compound in the given medium. Results: It was observed that, with an increase in lecithin content at constant STC concentration (3 mM), the amorphous solubility of atazanavir increased and crystallization was accelerated. However, the crystalline solubility remained fairly constant. Solubility values were higher in FaSSIF compared to Composite-SIF. Longer nucleation induction times were observed for atazanavir, ritonavir and tacrolimus in Composite-SIF compared to FaSSIF at equivalent supersaturation ratios. Conclusions: This study shows that variations in the composition of SIF can lead to differences in the solubility and crystallization tendency of drug molecules, both of which are critical when evaluating supersaturating systems.
Mesh-Begriff(e)	Algorithms ; Atazanavir Sulfate/chemistry ; Calcium Channel Blockers/chemistry ; Crystallization ; Dihydropyridines/chemistry ; HIV Protease Inhibitors/chemistry ; Humans ; Immunosuppressive Agents/chemistry ; Intestinal Secretions/chemistry ; Lecithins/chemistry ; Pharmaceutical Preparations/chemistry ; Ritonavir/chemistry ; Solubility ; Solutions/chemistry ; Tacrolimus/chemistry
Chemische Substanzen	Calcium Channel Blockers ; Dihydropyridines ; HIV Protease Inhibitors ; Immunosuppressive Agents ; Lecithins ; Pharmaceutical Preparations ; Solutions ; Atazanavir Sulfate (4MT4VIE29P) ; cilnidipine (97T5AZ1JIP) ; Ritonavir (O3J8G9O825) ; Tacrolimus (WM0HAQ4WNM)
Sprache	Englisch
Erscheinungsdatum	2018-06-18
Erscheinungsland	United States
Dokumenttyp	Journal Article
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-018-2441-2
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Exploiting the Phenomenon of Liquid-Liquid Phase Separation for Enhanced and Sustained Membrane Transport of a Poorly Water-Soluble Drug.

Indulkar, Anura S / Gao, Yi / Raina, Shweta A / Zhang, Geoff G Z / Taylor, Lynne S

Molecular pharmaceutics

2016 Band 13, Heft 6, Seite(n) 2059–2069

Abstract: Recent studies on aqueous supersaturated lipophilic drug solutions prepared by methods including antisolvent addition, pH swing, or dissolution of amorphous solid dispersions (ASDs) have demonstrated that when crystallization is slow, these systems ... ...

Abstract	Recent studies on aqueous supersaturated lipophilic drug solutions prepared by methods including antisolvent addition, pH swing, or dissolution of amorphous solid dispersions (ASDs) have demonstrated that when crystallization is slow, these systems undergo liquid-liquid phase separation (LLPS) when the concentration of the drug in the medium exceeds its amorphous solubility. Following LLPS, a metastable equilibrium is formed where the concentration of drug in the continuous phase corresponds to the amorphous solubility while the dispersed phase is composed of a nanosized drug-rich phase. It has been reasoned that the drug-rich phase may act as a reservoir, enabling the rate of passive transport of the drug across a membrane to be maintained at the maximum value for an extended period of time. Herein, using clotrimazole as a model drug, and a flow-through diffusion cell, the reservoir effect is demonstrated. Supersaturated clotrimazole solutions at concentrations below the amorphous solubility show a linear relationship between the maximum flux and the initial concentration. Once the concentration exceeds the amorphous solubility, the maximum flux achieved reaches a plateau. However, the duration for which the high flux persists was found to be highly dependent on the number of drug-rich nanodroplets present in the donor compartment. Macroscopic amorphous particles of clotrimazole did not lead to the same reservoir effect observed with the nanodroplets formed through the process of LLPS. A first-principles mathematical model was developed which was able to fit the experimental receiver concentration-time profiles for concentration regimes both below and above amorphous solubility, providing support for the contention that the nanodroplet phase does not directly diffuse across the membrane but, instead, rapidly replenishes the drug in the aqueous phase that has been removed by transport across the membrane. This study provides important insight into the properties of supersaturated solutions and how these might in turn impact oral absorption through effects on passive membrane transport rates.
Mesh-Begriff(e)	Biological Transport/physiology ; Chemistry, Pharmaceutical/methods ; Crystallization/methods ; Delayed-Action Preparations/chemistry ; Diffusion ; Membranes/metabolism ; Nanoparticles/chemistry ; Pharmaceutical Preparations/chemistry ; Solubility ; Solutions/chemistry ; Water/chemistry
Chemische Substanzen	Delayed-Action Preparations ; Pharmaceutical Preparations ; Solutions ; Water (059QF0KO0R)
Sprache	Englisch
Erscheinungsdatum	2016--06
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/acs.molpharmaceut.6b00202
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Using Environment-Sensitive Fluorescent Probes to Characterize Liquid-Liquid Phase Separation in Supersaturated Solutions of Poorly Water Soluble Compounds.

Raina, Shweta A / Alonzo, David E / Zhang, Geoff G Z / Gao, Yi / Taylor, Lynne S

Pharmaceutical research

2015 Band 32, Heft 11, Seite(n) 3660–3673

Abstract: Purpose: Highly supersaturated aqueous solutions of poorly soluble compounds can undergo liquid-liquid phase separation (LLPS) when the concentration exceeds the "amorphous solubility". This phenomenon has been widely observed during high throughput ... ...

Abstract	Purpose: Highly supersaturated aqueous solutions of poorly soluble compounds can undergo liquid-liquid phase separation (LLPS) when the concentration exceeds the "amorphous solubility". This phenomenon has been widely observed during high throughput screening of new molecular entities as well as during the dissolution of amorphous solid dispersions. In this study, we have evaluated the use of environment-sensitive fluorescence probes to investigate the formation and properties of the non-crystalline drug-rich aggregates formed in aqueous solutions as a result of LLPS. Methods: Six different environment-sensitive fluorophores were employed to study LLPS in highly supersaturated solutions of several model compounds, all dihydropyridine derivatives. Results: Each fluoroprobe exhibited a large hypsochromic shift with decreasing environment polarity. Upon drug aggregate formation, the probes partitioned into the drug-rich phase and exhibited changes in emission wavelength and intensity consistent with sensing a lower polarity environment. The LLPS onset concentrations determined using the fluorescence measurements were in good agreement with light scattering measurements as well as theoretically estimated amorphous solubility values. Conclusions: Environment-sensitive fluorescence probes are useful to help understand the phase behavior of highly supersaturated aqueous solutions, which in turn is important in the context of developing enabling formulations for poorly soluble compounds.
Mesh-Begriff(e)	Chemistry, Pharmaceutical/methods ; Crystallization ; Dihydropyridines/chemistry ; Fluorescent Dyes/chemistry ; High-Throughput Screening Assays ; Molecular Structure ; Pharmaceutical Preparations/chemistry ; Pharmaceutical Solutions/chemistry ; Phase Transition ; Solubility ; Water/chemistry
Chemische Substanzen	Dihydropyridines ; Fluorescent Dyes ; Pharmaceutical Preparations ; Pharmaceutical Solutions ; Water (059QF0KO0R)
Sprache	Englisch
Erscheinungsdatum	2015-11
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-015-1725-z
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Origin of Nanodroplet Formation Upon Dissolution of an Amorphous Solid Dispersion: A Mechanistic Isotope Scrambling Study.

Indulkar, Anura S / Waters, Jan E / Mo, Huaping / Gao, Yi / Raina, Shweta A / Zhang, Geoff G Z / Taylor, Lynne S

Journal of pharmaceutical sciences

2017 Band 106, Heft 8, Seite(n) 1998–2008

Abstract: It has been observed that certain amorphous solid dispersions (ASDs), upon dissolution, generate drug-rich amorphous nanodroplets. These nanodroplets, present as a dispersed phase, can potentially enhance oral bioavailability of poorly soluble drugs by ... ...

Abstract	It has been observed that certain amorphous solid dispersions (ASDs), upon dissolution, generate drug-rich amorphous nanodroplets. These nanodroplets, present as a dispersed phase, can potentially enhance oral bioavailability of poorly soluble drugs by serving as a drug reservoir that efficiently feeds the continuous aqueous solution phase following absorption of drug. The purpose of this study is to probe the formation mechanism of the nanodroplets. The model system studied was nifedipine (NFD) formulated as an ASD with hydroxypropyl methylcellulose E5 Premium LV or polyvinylpyrrolidone/vinyl acetate. Dissolution of ASDs prepared with proteated nifedipine (H-NFD) was carried out in a medium saturated with deuterated nifedipine (D-NFD) at the amorphous solubility. Upon dissolution, the H/D composition of NFD aqueous solution was determined using nuclear magnetic resonance spectroscopy. The results suggested that isotopic scrambling (equilibrium in the distribution of deuterated and proteated form of the drug) had occurred. Thus, as the H-NFD was brought into the aqueous solution via ASD dissolution, the drug concentration in solution exceeded the amorphous solubility. Subsequent precipitation of the drug, a process which does not differentiate H-NFD from D-NFD, generated NFD nanodroplets and resulted in redistribution of the isotopes. Thus, nanodroplets of NFD are formed due to dissolution of these homogenous ASDs followed by precipitation of the drug from aqueous solutions.
Mesh-Begriff(e)	Calcium Channel Blockers/chemistry ; Crystallization ; Drug Compounding ; Excipients/chemistry ; Hypromellose Derivatives/chemistry ; Magnetic Resonance Spectroscopy ; Nanostructures/chemistry ; Nifedipine/chemistry ; Povidone/chemistry ; Solubility ; Vinyl Compounds/chemistry
Chemische Substanzen	Calcium Channel Blockers ; Excipients ; Vinyl Compounds ; Hypromellose Derivatives (3NXW29V3WO) ; Povidone (FZ989GH94E) ; Nifedipine (I9ZF7L6G2L) ; vinyl acetate (L9MK238N77)
Sprache	Englisch
Erscheinungsdatum	2017-04-19
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3151-3
ISSN	1520-6017 ; 0022-3549
ISSN (online)	1520-6017
ISSN	0022-3549
DOI	10.1016/j.xphs.2017.04.015
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Impact of Micellar Surfactant on Supersaturation and Insight into Solubilization Mechanisms in Supersaturated Solutions of Atazanavir.

Indulkar, Anura S / Mo, Huaping / Gao, Yi / Raina, Shweta A / Zhang, Geoff G Z / Taylor, Lynne S

Pharmaceutical research

2017 Band 34, Heft 6, Seite(n) 1276–1295

Abstract: Purpose: The goals of this study were to determine: 1) the impact of surfactants on the "amorphous solubility"; 2) the thermodynamic supersaturation in the presence of surfactant micelles; 3) the mechanism of solute solubilization by surfactant micelles ...

Abstract	Purpose: The goals of this study were to determine: 1) the impact of surfactants on the "amorphous solubility"; 2) the thermodynamic supersaturation in the presence of surfactant micelles; 3) the mechanism of solute solubilization by surfactant micelles in supersaturated solutions. Methods: The crystalline and amorphous solubility of atazanavir was determined in the presence of varying concentrations of micellar sodium dodecyl sulfate (SDS). Flux measurements, using a side-by-side diffusion cell, were employed to determine the free and micellar-bound drug concentrations. The solubilization mechanism as a function of atazanavir concentration was probed using fluorescence spectroscopy. Pulsed gradient spin-echo proton nuclear magnetic resonance (PGSE-NMR) spectroscopy was used to determine the change in micelle size with a change in drug concentration. Results: Changes in the micelle/water partition coefficient, K Conclusions: Micellar solubilization of atazanavir is complex, with the solubilization mechanism changing with differences in the degree of (super)saturation. This can result in erroneous predictions of the amorphous solubility and thermodynamic supersaturation in the presence of solubilizing additives. This in turn hinders understanding of the driving force for phase transformations and membrane transport, which is essential to better understand supersaturating dosage forms.
Mesh-Begriff(e)	Atazanavir Sulfate/chemistry ; Kinetics ; Micelles ; Nanoparticles/chemistry ; Particle Size ; Sodium Dodecyl Sulfate/chemistry ; Solubility ; Solutions ; Spectrometry, Fluorescence ; Surface Properties ; Surface-Active Agents/chemistry ; Thermodynamics
Chemische Substanzen	Micelles ; Solutions ; Surface-Active Agents ; Sodium Dodecyl Sulfate (368GB5141J) ; Atazanavir Sulfate (4MT4VIE29P)
Sprache	Englisch
Erscheinungsdatum	2017-03-28
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-017-2144-0
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: FRET-based localization of fluorescent protein insertions within the ryanodine receptor type 1.

Raina, Shweta A / Tsai, Jeffrey / Samsó, Montserrat / Fessenden, James D

PloS one

2012 Band 7, Heft 6, Seite(n) e38594

Abstract: Fluorescent protein (FP) insertions have often been used to localize primary structure elements in mid-resolution 3D cryo electron microscopic (EM) maps of large protein complexes. However, little is known as to the precise spatial relationship between ... ...

Abstract	Fluorescent protein (FP) insertions have often been used to localize primary structure elements in mid-resolution 3D cryo electron microscopic (EM) maps of large protein complexes. However, little is known as to the precise spatial relationship between the location of the fused FP and its insertion site within a larger protein. To gain insights into these structural considerations, Förster resonance energy transfer (FRET) measurements were used to localize green fluorescent protein (GFP) insertions within the ryanodine receptor type 1 (RyR1), a large intracellular Ca(2+) release channel that plays a key role in skeletal muscle excitation contraction coupling. A series of full-length His-tagged GFP-RyR1 fusion constructs were created, expressed in human embryonic kidney (HEK)-293T cells and then complexed with Cy3NTA, a His-tag specific FRET acceptor. FRET efficiency values measured from each GFP donor to Cy3NTA bound to each His tag acceptor site were converted into intermolecular distances and the positions of each inserted GFP were then triangulated relative to a previously published X-ray crystal structure of a 559 amino acid RyR1 fragment. We observed that the chromophoric centers of fluorescent proteins inserted into RyR1 can be located as far as 45 Å from their insertion sites and that the fused proteins can also be located in internal cavities within RyR1. These findings should prove useful in interpreting structural results obtained in cryo EM maps using fusions of small fluorescent proteins. More accurate point-to-point distance information may be obtained using complementary orthogonal labeling systems that rely on fluorescent probes that bind directly to amino acid side chains.
Mesh-Begriff(e)	Calibration ; Cryoelectron Microscopy ; DNA, Complementary ; Fluorescence Resonance Energy Transfer ; Green Fluorescent Proteins/genetics ; HEK293 Cells ; Humans ; Models, Molecular ; Ryanodine Receptor Calcium Release Channel/chemistry ; Ryanodine Receptor Calcium Release Channel/genetics ; Ryanodine Receptor Calcium Release Channel/metabolism
Chemische Substanzen	DNA, Complementary ; Ryanodine Receptor Calcium Release Channel ; Green Fluorescent Proteins (147336-22-9)
Sprache	Englisch
Erscheinungsdatum	2012-06-13
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0038594
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Impact of polymers on the crystallization and phase transition kinetics of amorphous nifedipine during dissolution in aqueous media.

Raina, Shweta A / Alonzo, David E / Zhang, Geoff G Z / Gao, Yi / Taylor, Lynne S

Molecular pharmaceutics

2014 Band 11, Heft 10, Seite(n) 3565–3576

Abstract: The commercial and clinical success of amorphous solid dispersions (ASD) in overcoming the low bioavailability of poorly soluble molecules has generated momentum among pharmaceutical scientists to advance the fundamental understanding of these complex ... ...

Abstract	The commercial and clinical success of amorphous solid dispersions (ASD) in overcoming the low bioavailability of poorly soluble molecules has generated momentum among pharmaceutical scientists to advance the fundamental understanding of these complex systems. A major limitation of these formulations stems from the propensity of amorphous solids to crystallize upon exposure to aqueous media. This study was specifically focused on developing analytical techniques to evaluate the impact of polymers on the crystallization behavior during dissolution, which is critical in designing effective amorphous formulations. In the study, the crystallization and polymorphic conversions of a model compound, nifedipine, were explored in the absence and presence of polyvinylpyrrolidone (PVP), hydroxypropylmethyl cellulose (HPMC), and HPMC-acetate succinate (HPMC-AS). A combination of analytical approaches including Raman spectroscopy, polarized light microscopy, and chemometric techniques such as multivariate curve resolution (MCR) were used to evaluate the kinetics of crystallization and polymorphic transitions as well as to identify the primary route of crystallization, i.e., whether crystallization took place in the dissolving solid matrix or from the supersaturated solutions generated during dissolution. Pure amorphous nifedipine, when exposed to aqueous media, was found to crystallize rapidly from the amorphous matrix, even when polymers were present in the dissolution medium. Matrix crystallization was avoided when amorphous solid dispersions were prepared, however, crystallization from the solution phase was rapid. MCR was found to be an excellent data processing technique to deconvolute the complex phase transition behavior of nifedipine.
Mesh-Begriff(e)	Crystallization ; Hypromellose Derivatives/chemistry ; Kinetics ; Nifedipine/chemistry ; Phase Transition ; Polymers/chemistry ; Povidone/analogs & derivatives ; Povidone/chemistry ; Solubility ; Spectrum Analysis, Raman
Chemische Substanzen	Polymers ; polyvinylpolypyrrolidone (25249-54-1) ; Hypromellose Derivatives (3NXW29V3WO) ; Povidone (FZ989GH94E) ; Nifedipine (I9ZF7L6G2L)
Sprache	Englisch
Erscheinungsdatum	2014-10-06
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/mp500333v
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Classification of the crystallization behavior of amorphous active pharmaceutical ingredients in aqueous environments.

Van Eerdenbrugh, Bernard / Raina, Shweta / Hsieh, Yi-Ling / Augustijns, Patrick / Taylor, Lynne S

Pharmaceutical research

2013 Band 31, Heft 4, Seite(n) 969–982

Abstract: Purpose: To classify the crystallization behavior of amorphous active pharmaceutical ingredients (API) exposed to aqueous environments.: Methods: A set of approximately 50 chemically and physically diverse active pharmaceutical ingredients (APIs) was ...

Abstract	Purpose: To classify the crystallization behavior of amorphous active pharmaceutical ingredients (API) exposed to aqueous environments. Methods: A set of approximately 50 chemically and physically diverse active pharmaceutical ingredients (APIs) was selected for this study. Two experimental setups were employed to characterize the crystallization behavior of the amorphous API in an aqueous environment. For the first approach, precipitation, as evidenced by the development of turbidity, was induced using the solvent shift method, by mixing concentrated API solutions in DMSO with an aqueous buffer in a capillary. Subsequently, crystallization was monitored in situ over time using synchrotron radiation (simultaneous SAXS/WAXS beamline 12-ID-B at the Advanced Photon Source, Argonne National Laboratories, Argonne, IL). In the second approach, amorphous films were prepared by melt quenching; after adding buffer, crystallization was monitored with time using polarized light microscopy. Results: In general, the crystallization behavior of a given compound was similar irrespective of the experimental method employed. However, the crystallization behavior among different compounds varied significantly, ranging from immediate and complete crystallization to no observable crystallization over biorelevant time scales. Comparison of the observed behavior with previous studies of crystallization tendency in non-aqueous environments revealed that the crystallization tendency of individual APIs was somewhat similar regardless of the crystallization environment. Conclusions: API properties, rather than the method by which amorphous materials are generated, tend to dictate crystallization behavior in aqueous media.
Mesh-Begriff(e)	Crystallization ; Pharmaceutical Preparations/chemistry ; Pharmaceutical Preparations/classification ; Pharmaceutical Solutions/chemistry ; Pharmaceutical Solutions/classification ; Water/chemistry ; X-Ray Diffraction/methods
Chemische Substanzen	Pharmaceutical Preparations ; Pharmaceutical Solutions ; Water (059QF0KO0R)
Sprache	Englisch
Erscheinungsdatum	2013-11-23
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-013-1216-z
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Trends in the precipitation and crystallization behavior of supersaturated aqueous solutions of poorly water-soluble drugs assessed using synchrotron radiation.

Raina, Shweta A / Van Eerdenbrugh, Bernard / Alonzo, David E / Mo, Huaping / Zhang, Geoff G Z / Gao, Yi / Taylor, Lynne S

Journal of pharmaceutical sciences

2015 Band 104, Heft 6, Seite(n) 1981–1992

Abstract: Amorphous materials are high-energy solids that can potentially enhance the bioavailability of poorly soluble compounds. A major impediment to their widespread use as a formulation platform is the tendency of amorphous materials to crystallize. The aim ... ...

Abstract	Amorphous materials are high-energy solids that can potentially enhance the bioavailability of poorly soluble compounds. A major impediment to their widespread use as a formulation platform is the tendency of amorphous materials to crystallize. The aim of this study was to evaluate the relative crystallization tendency of six structural analogues belonging to the dihydropyridine class, in an aqueous environment in the absence and presence of polymers, using wide-angle X-ray scattering synchrotron radiation and polarized light microscopy. The crystallization behavior of precipitates generated from supersaturated solutions of the active pharmaceutical ingredients was found to be highly variable ranging from immediate to several hours in the absence of polymers. Polymers with intermediate hydrophilicity/hydrophobicity were found to substantially delay crystallization, whereas strongly hydrophilic or hydrophobic polymers were largely ineffective. Nuclear magnetic resonance spectroscopy experiments supported the supposition that polymers need to have affinity for both the drug-rich precipitate and the aqueous phase in order to be effective crystallization inhibitors. This study highlights the variability in the crystallization tendency of different compounds and provides insight into the mechanism of inhibition by polymeric additives.
Mesh-Begriff(e)	Calcium Channel Blockers/chemistry ; Chemical Precipitation ; Crystallization ; Dihydropyridines/chemistry ; Hydrophobic and Hydrophilic Interactions ; Polymers/chemistry ; Solubility ; Solutions/chemistry ; Synchrotrons ; Water/chemistry ; X-Ray Diffraction
Chemische Substanzen	Calcium Channel Blockers ; Dihydropyridines ; Polymers ; Solutions ; Water (059QF0KO0R) ; 1,4-dihydropyridine (7M8K3P6I89)
Sprache	Englisch
Erscheinungsdatum	2015-06
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3151-3
ISSN	1520-6017 ; 0022-3549
ISSN (online)	1520-6017
ISSN	0022-3549
DOI	10.1002/jps.24423
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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