Controlled drug release from polymeric delivery devices III: In vitro-in vivo correlation for intravaginal release of ethynodiol diacetate from silicone devices in rabbits

Chien, Yie W.; Mares, Stanley E.; Berg, John C.; Huber, Susan; Lambert, Howard J.; King, Kenneth F.

doi:10.1002/jps.2600641108

Cited by 32 publications

(5 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With some incubators, the shaking distance can also be adjusted. Changing any of these three variables will modify both the dynamics of fluid flow around the ring device and, in turn, the thickness of the diffusion boundary layer (the relatively static layer of fluid immediately adjacent to the ring surface)[59,[108][109][110]. In general, increasing the shaking speed or distance leads to increased rate of drug release, although there is very limited data reported in the literature on this topic[111].…”

mentioning

confidence: 99%

In vitro release testing methods for drug-releasing vaginal rings

Boyd

Variano

Spence

et al. 2019

Journal of Controlled Release

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 99%

In vitro release testing methods for drug-releasing vaginal rings

Boyd

Variano

Spence

et al. 2019

Journal of Controlled Release

View full text Add to dashboard Cite

show abstract

“…However, the measurement of vaginal levels in rabbits following microbicide gel application is routine, and may be useful in establishing ballpark levels for ring devices in the same model. Previous work by Chien et al presents historical precedence for using rabbits in evaluating sustained drug release from silicone intravaginal devices for both in vivo release determination and plasma PK [22]. Quantitation of drug levels in rabbit vaginal tissues, vaginal fluids, and plasma is considered essential for early preclinical evaluation of microbicide IVRs or IVR segments [24].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, an animal model that is relatively simple to use would enhance the ability to assess the performance of IVRs designed to release poorly water-soluble drugs such as UC781. A rabbit model has previously been reported to assess the in vivo release of steroid hormones from linear silicone devices [22].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of UC781-loaded intravaginal ring segments in rabbits: a comparison of polymer matrices

Clark

Kiser

Loxley

et al. 2011

Drug Deliv. and Transl. Res.

View full text Add to dashboard Cite

UC781 is a potent and poorly water-soluble nonnucleoside reverse transcriptase inhibitor being investigated as a potential microbicide for preventing sexual transmission of HIV-1. This study was designed to evaluate the in vivo release and pharmacokinetics of UC781 delivered from matrix-type intravaginal ring segments in rabbits. Three polymer matrices (polyurethane, ethylene vinyl acetate copolymer, and silicone elastomer) and two drug loadings (5 and 15 mg/segment) were evaluated in at least one of two independent studies for up to 28 days in vivo. Inter-study comparison of in vivo release, vaginal tissue, and plasma concentrations for similar formulations demonstrated good reproducibility of the animal model. Mean estimates for a 28-day in vivo release ranged from 0.35 to 3.17 mg UC781 per segment. Mean proximal vaginal tissue levels (adjacent to the IVR segment) were 8-410 ng/g and did not change significantly with time for most formulations. Distal vaginal tissue levels of UC781 were 6- to 49-fold lower than proximal tissue levels. Mean UC781 plasma levels were low for all formulations, at 0.09-0.58 ng/mL. All formulations resulted in similar UC781 concentrations in vaginal tissue and plasma, except the low loading polyurethane group which provided significantly lower levels. Loading dependent release and pharmacokinetics were only clearly observed for the polyurethane matrix. Based on these results, intravaginal ring segments loaded with UC781 led to vaginal tissue concentrations ranging from below to approximately two orders of magnitude higher than UC781's EC50 under in vitro conditions (2.8 ng/mL), with little influence by polymer matrix or UC781 loading. Moreover, these findings support the use of rabbit vaginal pharmacokinetic studies in preclinical testing of microbicide intravaginal rings.

show abstract

“…However, care need be taken that the carrier liquid itself does not diffuse out of the membrane along with the active agent. Chien et al (1975) observed that the release rate of ethynodiol diacetate from silicone matrices was strongly dependent on the agitation rate ( Fig. 2.26, in which is displayed the release rate of a series of devices loaded with different amounts of estriol (Baker et aI., 1979).…”

Section: Factors Influencing Diffusional Releasementioning

confidence: 99%

Controlled Release

Fan

Singh

1989

View full text Add to dashboard Cite

Controlled drug release from polymeric delivery devices III: In vitro-in vivo correlation for intravaginal release of ethynodiol diacetate from silicone devices in rabbits

Cited by 32 publications

References 5 publications

In vitro release testing methods for drug-releasing vaginal rings

In vitro release testing methods for drug-releasing vaginal rings

Pharmacokinetics of UC781-loaded intravaginal ring segments in rabbits: a comparison of polymer matrices

Controlled Release

Contact Info

Product

Resources

About