Effects of Solvents, Emulsions, Cosolvents, and Complexions on Ex Vivo Mouse Myometrial Contractility

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Abstract

A great need exists to develop tocolytic and uterotonic drugs that combat poor, labor-related maternal and fetal outcomes. A widely utilized method to assess novel compounds for their tocolytic and uterotonic efficacy is the isometric organ bath contractility assay. Unfortunately, water-insoluble compounds can be difficult to test using the physiological, buffer-based, organ bath assay. Common methods for overcoming solubility issues include solvent variation, cosolvency, surfactant or complexion use, and emulsification. However, these options for drug delivery or formulation can impact tissue function. Therefore, the goal of this study was to evaluate the ability of common solvents, surfactants, cosolvents, and emulsions to adequately solubilize compounds in the organ bath assay without affecting mouse myometrial contractility. We found that acetone, acetonitrile, and ethanol had the least effect, while dimethylacetamide, ethyl acetate, and isopropanol displayed the greatest inhibition of myometrial contractility based on area under the contractile curve analyses. The minimum concentration of surfactants, cosolvents, and human serum albumin required to solubilize nifedipine, a current tocolytic drug, resulted in extensive bubbling in the organ bath assay, precluding their use. Finally, we report that an oil-in-water base emulsion containing no drug has no statistical effect beyond the control (water), while the drug emulsion yielded the same potency and efficacy as the freely solubilized drug.

Supplementary Information

The online version contains supplementary material available at 10.1007/s43032-021-00576-5.

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Sandeep Kalepu, Vijaykumar Nekkanti (2015)

The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve efficacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical companies. This review covers the recent advances in the field of insoluble drug delivery and business prospects.

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Author and article information

Contributors

Jennifer Herington:

ORCID: http://orcid.org/0000-0001-7084-184X

Jennifer.l.herington@vumc.org

Journal

Journal ID (nlm-ta): Reprod Sci

Journal ID (iso-abbrev): Reprod Sci

Title: Reproductive Sciences

Publisher: Springer International Publishing (Cham )

ISSN (Print): 1933-7191

ISSN (Electronic): 1933-7205

Publication date (Electronic): 14 April 2021

Publication date PMC-release: 14 April 2021

Publication date Collection: February 2022

Volume: 29

Issue: 2

Pages: 586-595

Affiliations

[1 ]GRID grid.412807.8, ISNI 0000 0004 1936 9916, Department of Pediatrics, Division of Neonatology, , Vanderbilt University Medical Center, ; 2215B Garland Ave, 1125 Light Hall, Nashville, TN 37232 USA

[2 ]GRID grid.152326.1, ISNI 0000 0001 2264 7217, Department of Pharmacology, , Vanderbilt University, ; Nashville, TN USA

Author information

Jennifer Herington http://orcid.org/0000-0001-7084-184X

Article

Publisher ID: 576

DOI: 10.1007/s43032-021-00576-5

PMC ID: 8782813

PubMed ID: 33852137

SO-VID: fd1e6467-a61f-459b-85e8-7f980c2efe22

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 16 February 2021

Date accepted : 2 April 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100009633, Eunice Kennedy Shriver National Institute of Child Health and Human Development;

Award ID: HD088830

Award ID: HD098213

Award Recipient : Jennifer Herington

Custom metadata

Keywords: emulsion,isometric contractility,uterus,solvents,tissue bath,tocolytic

Data availability:

Keywords: emulsion, isometric contractility, uterus, solvents, tissue bath, tocolytic

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