Physical Stability of Salts of Weak Bases in the Solid-State

Stephenson, Gregory A.; Aburub, Aktham; Woods, Timothy A.

doi:10.1002/jps.22405

Cited by 141 publications

(88 citation statements)

References 16 publications

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“…Of special importance is the intrinsic solubility (S 0 ), i.e. the solubility of the drug when unionized 1,15 . The values of pK a and S 0 dictate the ease with which formulations are obtained for oral gavage and intravenous (i.v.)…”

Section: Research Articlementioning

confidence: 99%

“…Salt formation is one of the primary approaches used to modify the physical properties of a drug substance 1,15 . Here, in order to investigate alternatives to the free base, with the aim of finding a drug compound with optimal physicochemical properties (primarily higher melting point), a salt screen was performed.…”

Section: Solid-state Properties Of the Free Base Of Azd1305mentioning

confidence: 99%

“…The most widely used software is ACDLabs (Advanced Chemistry Development) 14 . As a minimum requirement during early formulation development, the solubility and pK a must be determined 1,15 . It is well known…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Preformulation evaluation of AZD1305, an oxabispidine intended for oral and intravenous treatment

Sigfridsson¹,

Lundqvist

Ohlson

2011

Drug Development and Industrial Pharmacy

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Section: Research Articlementioning

confidence: 99%

Section: Solid-state Properties Of the Free Base Of Azd1305mentioning

confidence: 99%

See 1 more Smart Citation

Preformulation evaluation of AZD1305, an oxabispidine intended for oral and intravenous treatment

Sigfridsson¹,

Lundqvist

Ohlson

2011

Drug Development and Industrial Pharmacy

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“…Although various salts of ABZ have been prepared and characterized in the past (Paulekuhn et al 2013), the relatively low pKa makes ABZ salts sensitive to disproportionation (e.g. Stephenson et al 2011). After considering various counter-ions, the sulfate salt of ABZ was selected to be used, based on its comparatively better crystallinity and stability characteristics.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System

Kourentas

Vertzoni

Khadra

et al. 2016

Journal of Pharmaceutical Sciences

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This version is available at https://strathprints.strath.ac.uk/58946/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Strathprints administrator: strathprints@strath.ac.ukThe Strathprints institutional repository (https://strathprints.strath.ac.uk) is a digital archive of University of Strathclyde research outputs. It has been developed to disseminate open access research outputs, expose data about those outputs, and enable the management and persistent access to Strathclyde's intellectual output. AbstractAn in vitro biorelevant transfer (BioGIT) system was assessed for its ability to mimic recently reported albendazole concentrations in human upper small intestine after administration of free base suspensions to fasted adults in absence and in presence of supersaturation promoting excipients (hydroxypropylmethylcellulose and lipidic self-emulsifying vehicles).The in vitro method was then used to evaluate the likely impact of using the sulfate salt on albendazole concentrations in upper small intestine. In addition, BioGIT data were compared with equilibrium solubility data of the salt and the free base in human aspirates and biorelevant media. The BioGIT system adequately mimicked the average albendazole gastrointestinal transfer process and in vivo concentrations in upper small intestine after administration of the free base suspensions to fasted adults. However, the degree of supersaturation seen initially in the duodenuum was greater in-vitro than in-vivo.Albendazole sulfate resulted in minimal increase of albendazole concentrations in the duodenal compartment of the BioGIT, despite improved equilibrium solubility observed in human aspirates and biorelevant media, indicating that the use of a salt is unlikely to lead to any significant oral absorption advantage for albendazole.3

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“…The incorporation of pH modifiers in the dosage form can alter the microenvironmental pH. Microenvironment is a term used to represent a microscopic layer surrounding a solid particle in which the solid forms a saturated solution of adsorbed water 37 . The microenvironmental pH would affect the performance of the solid dosage form, such as the chemical stability of the drug substance and the dissolution profile 38 .…”

Section: Cyclodextrin Complexationmentioning

confidence: 99%

Bioavailability and Bioequivalence Study in Correlation of Biopharmaceutics Classification System (Bcs) and Possible Modification

Kshirsagar¹,

Shikare²,

Shaikh³

2013

J Pharm Sci Innov.

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In the last decade, the regulatory bioequivalence (BE) requirements of drug products have undergone major changes. Now a day the bioavailability and bioequivalence study is emerging area in the generic world. Today, the discovery of drug substances with increasing lipophilicity and resultant poor aqueous solubility is a more and more common problem in the development of orally administered new formulations. The Biopharmaceutics Classification System (BCS) is the technique used to differentiate the drugs on the basis of their solubility and permeability is a guide for predicting the intestinal drug absorption. The knowledge of the BCS characteristics of a drug in a formulation can also be utilized by the formulation scientist to develop a more optimized dosage form based on fundamental mechanistic, rather than empirical, information. The possible changes in the class three and four drugs we increase the solubility and permeability and achieve great success in the field of generic market. Here in this review we compile the information on all four class drugs of BCS and their possible modification.

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Physical Stability of Salts of Weak Bases in the Solid-State

Cited by 141 publications

References 16 publications

Preformulation evaluation of AZD1305, an oxabispidine intended for oral and intravenous treatment

Preformulation evaluation of AZD1305, an oxabispidine intended for oral and intravenous treatment

Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System

Bioavailability and Bioequivalence Study in Correlation of Biopharmaceutics Classification System (Bcs) and Possible Modification

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