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Article: Unexpected Stability of a Prodrug to Enzymatic Hydrolysis within a Hydrated HPMC Matrix Tablet.

Hanley, Sarah / Brown, Jonathan / Timmins, Peter / Davies, Catrin / Dennis, Andrew

2022 Volume 14, Issue 10

Abstract: The uptake of alkaline phosphate present in dissolution medium into a hydrating hydroxypropyl methylcellulose matrix tablet and that its activity was retained therein was demonstrated. This presents a risk to the stability of prodrugs that are substrates ...

Abstract	The uptake of alkaline phosphate present in dissolution medium into a hydrating hydroxypropyl methylcellulose matrix tablet and that its activity was retained therein was demonstrated. This presents a risk to the stability of prodrugs that are substrates of this enzyme such as phosphonooxymethyl derivative prodrugs. It was found that fostemsavir, a phosphonooxymethyl derivative prodrug being developed for the treatment of HIV-1 infection, was unexpectedly resistant to hydrolysis within a hydrated HPMC matrix when subjected to drug release testing in media containing alkaline phosphatase. Studies indicated that this was not due to microenvironmental pH effects, osmolality effects or effective phosphate concentration effects associated with the presence of the prodrug. That the prodrug and not its parent could affect enzyme activity in a concentration dependent manner, and that another phosphate ester prodrug fosphenytoin did not inhibit alkaline phosphatase activity within a hydrated HPMC matrix suggested that the unexpected stability of the HIV-1 therapy prodrug may be associated with the ability of the phosphate group-containing compound itself to inhibit the enzyme at the concentrations it exists at in the hydrated dosage form and so enables the development of the compound in this type of dosage form.
Language	English
Publishing date	2022-10-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14102222
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Taking a break: The effect of taking a vacation from Facebook and Instagram on subjective well-being.

Hanley, Sarah M / Watt, Susan E / Coventry, William

PloS one

2019 Volume 14, Issue 6, Page(s) e0217743

Abstract: Social Networking Sites (SNS) such as Facebook and Instagram have relocated a large portion of people's social lives online, but can be intrusive and create social disturbances. Many people therefore consider taking an "SNS vacation." We investigated the ...

Abstract	Social Networking Sites (SNS) such as Facebook and Instagram have relocated a large portion of people's social lives online, but can be intrusive and create social disturbances. Many people therefore consider taking an "SNS vacation." We investigated the effects of a one-week vacation from both Facebook and Instagram on subjective well-being, and whether this would vary for passive or active SNS users. Usage amount was measured objectively, using RescueTime software, to circumvent issues of self-report. Usage style was identified at pre-test, and SNS users with a more active or more passive usage style were assigned in equal numbers to the conditions of one-week SNS vacation (n = 40) or no SNS vacation (n = 38). Subjective well-being (life satisfaction, positive affect, and negative affect) was measured before and after the vacation period. At pre-test, more active SNS use was found to correlate positively with life satisfaction and positive affect, whereas more passive SNS use correlated positively with life satisfaction, but not positive affect. Surprisingly, at post-test the SNS vacation resulted in lower positive affect for active users and had no significant effects for passive users. This result is contrary to popular expectation, and indicates that SNS usage can be beneficial for active users. We suggest that SNS users should be educated in the benefits of an active usage style and that future research should consider the possibility of SNS addiction among more active users.
MeSH term(s)	Adolescent ; Adult ; Female ; Humans ; Male ; Mental Health ; Middle Aged ; Principal Component Analysis ; Regression Analysis ; Social Media ; Young Adult
Language	English
Publishing date	2019-06-06
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0217743
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Safety and effectiveness of a milk ladder for managing children with IgE-mediated milk allergy.

Ah Heng, Tessa / Cronin, Caoimhe / Flores, Laura / Meyer, Francois / O'Sullivan, Meg / McGinley, Anne Marie / Hanley, Sarah / McKiernan, Anne / D'Art, Yvonne / Hourihane, Jonathan O' B / Velasco, Roberto / Trujillo, Juan

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

2023 Volume 54, Issue 1, Page(s) 61–63

MeSH term(s)	Child ; Humans ; Infant ; Animals ; Milk Hypersensitivity/therapy ; Milk/adverse effects ; Immunoglobulin E ; Allergens ; Milk Proteins/adverse effects
Chemical Substances	Immunoglobulin E (37341-29-0) ; Allergens ; Milk Proteins
Language	English
Publishing date	2023-11-09
Publishing country	England
Document type	Journal Article
ZDB-ID	645204-8
ISSN	1365-2222 ; 0954-7894 ; 0960-2178
ISSN (online)	1365-2222
ISSN	0954-7894 ; 0960-2178
DOI	10.1111/cea.14419
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Zs.A 767: Show issues

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Article ; Online: Advances in mechanistic understanding of release rate control mechanisms of extended-release hydrophilic matrix tablets.

Timmins, Peter / Desai, Divyakant / Chen, Wei / Wray, Patrick / Brown, Jonathan / Hanley, Sarah

Therapeutic delivery

2016 Volume 7, Issue 8, Page(s) 553–572

Abstract: Approaches to characterizing and developing understanding around the mechanisms that control the release of drugs from hydrophilic matrix tablets are reviewed. While historical context is provided and direct physical characterization methods are ... ...

Abstract	Approaches to characterizing and developing understanding around the mechanisms that control the release of drugs from hydrophilic matrix tablets are reviewed. While historical context is provided and direct physical characterization methods are described, recent advances including the role of percolation thresholds, the application on magnetic resonance and other spectroscopic imaging techniques are considered. The influence of polymer and dosage form characteristics are reviewed. The utility of mathematical modeling is described. Finally, how all the information derived from applying the developed mechanistic understanding from all of these tools can be brought together to develop a robust and reliable hydrophilic matrix extended-release tablet formulation is proposed.
Language	English
Publishing date	2016-08
Publishing country	England
Document type	Journal Article
ISSN	2041-6008
ISSN (online)	2041-6008
DOI	10.4155/tde-2016-0026
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Article ; Online: A novel co-processing method to manufacture an API for extended release formulation via formation of agglomerates of active ingredient and hydroxypropyl methylcellulose during crystallization.

Rosenbaum, Tamar / Erdemir, Deniz / Chang, Shih-Ying / Kientzler, Don / Wang, Steve / Chan, Steven H / Brown, Jonathan / Hanley, Sarah / Kiang, San

Drug development and industrial pharmacy

2018 Volume 44, Issue 10, Page(s) 1606–1612

Abstract: A novel process for generating agglomerates of active pharmaceutical ingredient (API) and polymer by swelling the polymer in a water/organic mixture has been developed to address formulation issues resulting from a water sensitive, high drug load API ... ...

Abstract	A novel process for generating agglomerates of active pharmaceutical ingredient (API) and polymer by swelling the polymer in a water/organic mixture has been developed to address formulation issues resulting from a water sensitive, high drug load API with poor powder properties. Initially, the API is dissolved in water, following which hydroxypropyl methylcellulose (HPMC) is added, resulting in the imbibing of water, along with the dissolved API, into the HPMC matrix. The addition of acetone and isopropyl acetate (anti-solvents) then causes the API to crystallize inside and on the surface of HPMC agglomerates. The process was scaled up to 20 kg scale. The agglomerates of API and HPMC generated by this process are ∼350 µm diameter, robust, and have significantly better flow than the API as measured by Erweka flow testing. These agglomerates exhibit improved bulk density, acceptable chemical stability, and high compressibility. The agglomerates process well through roller compaction and tableting, with no flow or sticking issues. This process is potentially adaptable to other APIs with similar attributes.
MeSH term(s)	Chemistry, Pharmaceutical/methods ; Crystallization ; Delayed-Action Preparations/chemical synthesis ; Delayed-Action Preparations/pharmacokinetics ; Drug Compounding ; Drug Liberation ; Hypromellose Derivatives/chemical synthesis ; Hypromellose Derivatives/pharmacokinetics
Chemical Substances	Delayed-Action Preparations ; Hypromellose Derivatives (3NXW29V3WO)
Language	English
Publishing date	2018-08-14
Publishing country	England
Document type	Journal Article
ZDB-ID	751874-2
ISSN	1520-5762 ; 0363-9045
ISSN (online)	1520-5762
ISSN	0363-9045
DOI	10.1080/03639045.2018.1483386
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Zs.A 1335: Show issues

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Article: Imaging of the Effect of Alcohol-Containing Media on the Performance of Hypromellose Hydrophilic Matrix Tablets: Comparison of Direct Compression and Regular Grades of Polymer.

Mawla, Nihad / Hanley, Sarah / Walton, Karl / Kaialy, Waseem / Hussain, Tariq / Ward, Adam / Brown, Jonathan / Conway, Barbara R / Timmins, Peter / Asare-Addo, Kofi

Pharmaceutics

2020 Volume 12, Issue 9

Abstract: As the ingestion of drug products with alcohol could have adverse effects on the release of drugs from dosage forms, it is important to understand the mechanisms underpinning the influence on drug release by evaluating the effect of alcohol-containing ... ...

Abstract	As the ingestion of drug products with alcohol could have adverse effects on the release of drugs from dosage forms, it is important to understand the mechanisms underpinning the influence on drug release by evaluating the effect of alcohol-containing media on the behaviour of pharmaceutical excipients. In this work, the effect of hydroalcoholic media containing up to 40%
Language	English
Publishing date	2020-09-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics12090889
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Article ; Online: Dissolution testing of modified release products with biorelevant media: An OrBiTo ring study using the USP apparatus III and IV.

European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V

2020 Volume 156, Page(s) 40–49

Abstract: During the OrBiTo project, our knowledge on the gastrointestinal environment has improved substantially and biorelevant media composition have been refined. The aim of this study was to propose optimized biorelevant testing conditions for modified ... ...

Abstract	During the OrBiTo project, our knowledge on the gastrointestinal environment has improved substantially and biorelevant media composition have been refined. The aim of this study was to propose optimized biorelevant testing conditions for modified release products, to evaluate the reproducibility of the optimized compendial apparatus III (USP apparatus III) and compendial apparatus IV (USP apparatus IV, open-loop mode) dissolution methods and to evaluate the usefulness of these methods to forecast the direction of food effects, if any, based on the results of two «ring» studies and by using two model modified release (MR) products, Ciproxin / Cipro XR and COREG CR. Six OrBiTo partners participated in each of the ring studies. All laboratories were provided with standard protocols, pure drug substance, and dose units. For the USP apparatus III, the dissolution methods applied to Ciproxin / Cipro XR, a monolithic MR product of an active pharmaceutical ingredient (API) with moderate aqueous solubility, were robust with low intra- and inter-laboratory data variability. Data from all partners were in line on a qualitative basis with food effect data in humans. For the USP apparatus IV, the dissolution methods applied to COREG CR, a multiparticulate, pH dependent, MR product of an API with low and pH dependent solubility led to high intra- and inter- laboratory data variability. Data from all partners were in line, on a qualitative basis, with the previously observed food effects in humans.
MeSH term(s)	Biological Availability ; Chemistry, Pharmaceutical/methods ; Ciprofloxacin/administration & dosage ; Ciprofloxacin/chemistry ; Ciprofloxacin/pharmacokinetics ; Drug Combinations ; Drug Liberation/physiology ; Food-Drug Interactions/physiology ; Gastrointestinal Tract/drug effects ; Gastrointestinal Tract/physiology ; Humans ; Hydrocortisone/chemistry ; Hydrocortisone/pharmacokinetics ; Solubility
Chemical Substances	Drug Combinations ; ciprofloxacin, hydrocortisone drug combination ; Ciprofloxacin (5E8K9I0O4U) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2020-08-31
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1065368-5
ISSN	1873-3441 ; 0939-6411
ISSN (online)	1873-3441
ISSN	0939-6411
DOI	10.1016/j.ejpb.2020.08.025
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Zs.B 1651: Show issues

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Article ; Online: Effect of hyperoxia on serine phosphorylation of apoptotic proteins in mitochondrial membranes of the cerebral cortex of newborn piglets.

Brutus, Nadege A / Hanley, Sarah / Ashraf, Qazi M / Mishra, Om P / Delivoria-Papadopoulos, Maria

Neurochemical research

2009 Volume 34, Issue 7, Page(s) 1219–1225

Abstract: Previous studies have shown that hyperoxia results in cerebral cortical neuronal apoptosis. Studies have also shown that phosphorylation of anti-apoptotic proteins Bcl-2 and Bcl-xl results in loss of their anti-apoptotic potential leading to alteration ... ...

Abstract	Previous studies have shown that hyperoxia results in cerebral cortical neuronal apoptosis. Studies have also shown that phosphorylation of anti-apoptotic proteins Bcl-2 and Bcl-xl results in loss of their anti-apoptotic potential leading to alteration in mitochondrial membrane permeability and the release of apoptogenic proteins in the neuronal cell of the newborn piglets. The present study tests the hypothesis that cerebral hyperoxia will result in increased serine phosphorylation of apoptotic proteins Bcl-2, Bcl-xl, Bax, and Bad in the mitochondrial membranes of the cerebral cortex of newborn piglets. Twelve newborn piglets were divided into normoxic (Nx, n = 6) exposed to an FiO(2) of 0.21 for 1 h and hyperoxic (Hyx, n = 6) exposed to FiO(2) of 1.0 for 1 h. In the Hyx group, PaO(2) was maintained above 400 mmHg while the Nx group was kept at 80-100 mmHg. Cerebral cortical tissue was harvested and mitochondrial fractions were isolated. Mitochondrial membrane proteins were separated using 12% SDS-PAGE, and probed with anti-serine phosphorylated Bcl-2, Bcl-xl, Bax, and Bad antibodies. Protein bands were detected, analyzed by imaging densitometry and density expressed as absorbance (OD x mm(2)). Phosphorylated Bcl-2 (p-Bcl-2) protein density (OD x mm(2)) was 81.81 +/- 9.24 in Nx and 158.34 +/- 10.66 in Hyx (P < 0.05). Phosphorylated Bcl-xl (p-Bcl-xl) protein density was 52.98 +/- 3.59 in Nx and 99.62 +/- 18.22 in Hyx (P < 0.05). Phosphorylated Bax (p-Bax) protein was 161.13 +/- 6.27 in Nx and 174.21 +/- 15.95 in Hyx (P = NS). Phosphorylated Bad (p-Bad) protein was 166.24 +/- 9.47 in Nx 155.38 +/- 12.32 in Hyx (P = NS). The data show that there is a significant increase in serine phosphorylation of Bcl-2 and Bcl-xl proteins while phosphorylation of Bad and Bax proteins were not altered during hyperoxia in the mitochondrial fraction of the cerebral cortex of newborn piglets. We conclude that hyperoxia results in differential post-translational modification of anti-apoptotic proteins Bcl-2 and Bcl-xl as compared to pro-apoptotic proteins Bax and Bad in mitochondria. We speculate that phosphorylation of Bcl-2 and Bcl-xl will result in loss of their anti-apoptotic potential by preventing their dimerization with Bax leading to activation of the caspase cascade of neuronal death.
MeSH term(s)	Animals ; Animals, Newborn ; Apoptosis/drug effects ; Apoptosis/physiology ; Cerebral Cortex/drug effects ; Cerebral Cortex/metabolism ; Cerebral Cortex/ultrastructure ; Hyperoxia/physiopathology ; Mitochondrial Membranes/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Serine/metabolism ; Swine ; bcl-2-Associated X Protein/metabolism ; bcl-Associated Death Protein/metabolism ; bcl-X Protein/metabolism
Chemical Substances	Proto-Oncogene Proteins c-bcl-2 ; bcl-2-Associated X Protein ; bcl-Associated Death Protein ; bcl-X Protein ; Serine (452VLY9402)
Language	English
Publishing date	2009-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	199335-5
ISSN	1573-6903 ; 0364-3190
ISSN (online)	1573-6903
ISSN	0364-3190
DOI	10.1007/s11064-008-9898-z
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 1368: Show issues

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Book: The "Lit de justice" of the kings of France

Hanley, Sarah

constitutional ideology in legend, ritual, and discourse

(Studies presented to the International Commission for the History of Representative and Parliamentary Institutions ; 65)

1983

Author's details	Sarah Hanley
Series title	Studies presented to the International Commission for the History of Representative and Parliamentary Institutions ; 65
Keywords	Constitutional history ; Lit de justice/History ; Rites and ceremonies/History
Language	English
Size	XIII, 388 S., Ill., graph. Darst.
Publisher	Princeton Univ. Pr
Publishing place	Princeton, NJ
Document type	Book
Note	Bibliography: p. [355]-371
ISBN	0691053820 ; 9780691053820
Database	Former special subject collection: coastal and deep sea fishing

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