Mechanical testing methods for drug-releasing vaginal rings

McCoy, Clare; Millar, Bronagh; Murphy, Diarmaid J.; Blanda, Wendy; Hansraj, Bashir; Devlin, Bríd; Malcolm, R. Karl; Boyd, Peter

doi:10.1016/j.ijpharm.2019.01.026

Cited by 25 publications

(23 citation statements)

References 29 publications

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“…Batches of rings were manufactured and their mechanical properties evaluated using a range of custom mechanical tests [45]. The force required to compress ring devices by 5 mm was measured using a Texture Analyser (TA-XTPlus, Stable Microsystems, UK), fitted with a 30 kg load cell and Texture Exponent (TEE32) 32 software, and using a custom ring holder.…”

Section: Methodsmentioning

confidence: 99%

Vaginal rings with exposed cores for sustained delivery of the HIV CCR5 inhibitor 5P12-RANTES

McBride

Boyd

Dias

et al. 2019

Journal of Controlled Release

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Antiretroviral-releasing vaginal rings are at the forefront of ongoing efforts to develop microbicide-based strategies for prevention of heterosexual transmission of the human immunodeficiency virus (HIV). However, traditional ring designs are generally only useful for vaginal administration of relatively potent, lipophilic, and small molecular weight drug molecules that have sufficient permeability in the non-biodegradable silicone elastomer or thermoplastic polymers. Here, we report a novel, easy-to-manufacture ‘exposed-core’ vaginal ring that provides sustained release of the protein microbicide candidate 5P12-RANTES, an experimental chemokine analogue that potently blocks the HIV CCR5 coreceptor. In vitro release, mechanical, and stability testing demonstrated the utility and practicality of this novel ring design. In a sheep pharmacokinetic model, a ring containing two ¼-length excipient-modified silicone elastomer cores – each containing lyophilised 5P12-RANTES and exposed to the external environment by two large windows – provided sustained concentrations of 5P12-RANTES in vaginal fluid and vaginal tissue between 10 and 10,000 ng/g over 28days, at least 50 and up to 50,000 times the reported in vitro IC50 value.

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Section: Methodsmentioning

confidence: 99%

Vaginal rings with exposed cores for sustained delivery of the HIV CCR5 inhibitor 5P12-RANTES

McBride

Boyd

Dias

et al. 2019

Journal of Controlled Release

Self Cite

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“…[7,8]. Mechanical testing is also considered an important product quality test for drug-releasing vaginal rings [9,10]. By comparison, performance tests for drug products invariably involve assessment of in vitro drug release.…”

Section: Introductionmentioning

confidence: 99%

In vitro release testing methods for drug-releasing vaginal rings

Boyd

Variano

Spence

et al. 2019

Journal of Controlled Release

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Drug-releasing vaginal rings are torus-shaped devices, generally fabricated from thermoplastics or silicone elastomers, used to administer pharmaceutical drugs to the human vagina for periods typically ranging from three weeks to twelve months. One of the most important product performance tests for vaginal rings is the in vitro release test. Although it has been fifty years since the a vaginal ring device was first described in the scientific literature, and despite seven drug-releasing vaginal rings having been approved for market, there is no universally accepted method for testing in vitro drug release, and only one non-compendial shaking incubator method (for the estradiol-releasing ring Estring ®) is described in the US Food and Drug Administration's Dissolution Methods Database. Here, for the first time, we critically review the diverse range of test methods that have been described in the scientific literature for testing in vitro release of drugreleasing vaginal rings. Issues around in vitro-in vivo correlation and modelling of in vitro release data are also discussed.

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“…Certain properties and physical processes which occur when manufacturing IVRs are limiting factors which influence the rate of drug release. Flexibility and transparency are important physical attributes that need to be considered when designing intravaginal rings [32]. Polymer materials are selected to manufacture IVRs because of their flexibility; their use depends on the grade and composition of the polymer [33].…”

Section: Selection Of Materialsmentioning

confidence: 99%

Development of Hormonal Intravaginal Rings: Technology and Challenges

Rafiei

Tabesh

Farzad

et al. 2021

Geburtshilfe Frauenheilkd

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Intravaginal rings (IVRs) are minimally invasive polymeric devices specifically designed to be used for the sustained and prolonged release of various type of drugs such as hormones. One of the benefits of using topical drug delivery systems (e.g., IVRs) is the fact that systemic drug delivery may cause drug resistance due to elevated drug levels. Topical drug delivery also provides higher concentrations of the drug to the target site and has fewer side effects. In addition, when a drug is administered vaginally, the hepatic first-pass effect is avoided, resulting in higher absorption. Contraception and treatments for specific diseases such as endometriosis and hormone deficiencies can be improved by the administration of hormones via an IVR. This article aims to classify and compare various designs of commercially available and non-commercial hormonal IVRs and to analyze their performance. Current challenges affecting the development of IVRs are investigated, and proposed solutions are discussed. A comprehensive search of publications in MEDLINE/PubMed and of commercial product data of IVRs was performed, and the materials, designs, performance, and applications (e.g., contraception, endometriosis, estrogen deficiency and urogenital atrophy) of hormonal IVRs were thoroughly evaluated. Most hormonal IVRs administer female sex hormones, i.e., estrogen and progestogens. In terms of material, IVRs are divided into 3 main groups: silicone, polyurethane, and polyethylene-co-vinyl acetate IVRs. As regards their design, there are 4 major designs for IVRs which strongly affect their performance and the timing and rate of hormone release. Important challenges include reducing the burst release and maintaining the bioavailability of hormones at their site of action over a prolonged period of administration as well as lowering production costs. Hormonal IVRs are a promising method which could be used to facilitate combination therapies by administering multiple drugs in a single IVR while eliminating the side effects of conventional drug administration methods. IVRs could considerably improve womenʼs quality of life all over the world within a short period of time.

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Mechanical testing methods for drug-releasing vaginal rings

Cited by 25 publications

References 29 publications

Vaginal rings with exposed cores for sustained delivery of the HIV CCR5 inhibitor 5P12-RANTES

Vaginal rings with exposed cores for sustained delivery of the HIV CCR5 inhibitor 5P12-RANTES

In vitro release testing methods for drug-releasing vaginal rings

Development of Hormonal Intravaginal Rings: Technology and Challenges

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