Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel

Boyd, Peter; Fetherston, Susan; McCoy, Clare; Major, Ian; Murphy, Diarmaid J.; Kumar, Sandeep; Holt, Jonathan; Brimer, Andrew; Blanda, Wendy; Devlin, Bríd; Malcolm, R. Karl

doi:10.1016/j.ijpharm.2016.07.051

Cited by 42 publications

(54 citation statements)

References 54 publications

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“…Silicone elastomer matrix-type VRs (Fig. 1A) containing various loadings of ISMN (100, 500 and 1000 mg per ring) were manufactured on a laboratory-scale injection molding machine, according to well-established and previously reported manufacturing protocols (Boyd et al, 2016;Fetherston et al, 2013). Briefly, the required amounts of ISMN were added to both Parts A and B of the MED-4320 addition-cure silicone elastomer system contained in custom screw-cap polypropylene containers, and the contents of each container individually mixed using a Dual Asymmetric Centrifuge (DAC) mixer (SpeedMixerTM DAC 150 FVZ-K, Hauschild, Germany) for 30 s at 3000 rpm.…”

Section: Manufacture Of Vaginal Ringsmentioning

confidence: 99%

“…Silicone elastomer reservoir-type VRs (Fig. 1B) -comprising ISMN (7% w/w) or MP (0.2% w/w) in a central core, with the core encapsulated with a silicone elastomer sheath -were similarly manufactured by injection molding via a previously described three-step process (Boyd et al, 2016). Briefly, active silicone elastomer mixtures, prepared as described for the matrix-type rings, were injected into a core ring mold assembly ( Fig.…”

Section: Manufacture Of Vaginal Ringsmentioning

confidence: 99%

“…Thermal analysis of ISMN, MP and samples taken from the drug-loaded rings was performed using differential scanning calorimetry (DSC; TA Instruments Q100; 50 mL min -1 nitrogen flow; -70 o C to 150 o C at a rate of 10 o C min -1 ) to probe the nature of the drugs within the rings, following established methods (Boyd et al, 2016;Fetherston et al, 2013).…”

Section: Differential Scanning Calorimetrymentioning

confidence: 99%

“…Matrix-type rings contain the drug distributed uniformly throughout the entire volume of the ring (Fig. 1A), and typically exhibit declining release rates with time (Boyd et al, 2016;Fetherston et al, 2013;Malcolm et al, 2016). Reservoir rings contain a drug-loaded core and a non-medicated membrane (Fig.…”

Section: Design and Manufacture Of Ringsmentioning

confidence: 99%

See 3 more Smart Citations

Intravaginal rings for continuous low-dose administration of cervical ripening agents

Wang

Boyd

Hunter³

et al. 2018

International Journal of Pharmaceutics

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Intravaginal rings (VRs) have been widely reported for administration of pharmaceutical drugs - most notably estrogens, progestogens and antiretrovirals - to the vagina for clinical benefit. Here, for the first time, we describe the design, manufacture and preclinical testing of VRs for sustained/controlled release of the cervical ripening agents isosorbide mononitrate (ISMN) and misoprostol (MP), either singly or in combination. Matrix-type silicone elastomer VRs containing ISMN showed declining daily release rates, ranging from 31 to 168 mg (Day 1) to 3-25 mg (Day 11). Novel orifice-type rings, in which a MP-containing silicone elastomer core is partially exposed to the external environment by overmolding with a non-medicated silicone elastomer sheath containing orifices, provided relatively constant daily MP release rates over 14 days (∼20 or 60 μg/day depending on the formulation type). Combination VRs offered simultaneous release of both ISMN and MP over 14 days, with an almost constant MP release rate (60 μg/day) and steadily declining daily ISMN release (295 mg on Day 1 and 24 mg on Day 11). The VR design can be readily tailored to provide sustained or controlled release of ISMN and MP at rates potentially useful for cervical ripening.

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Section: Manufacture Of Vaginal Ringsmentioning

confidence: 99%

Section: Manufacture Of Vaginal Ringsmentioning

confidence: 99%

Section: Differential Scanning Calorimetrymentioning

confidence: 99%

Section: Design and Manufacture Of Ringsmentioning

confidence: 99%

See 2 more Smart Citations

Intravaginal rings for continuous low-dose administration of cervical ripening agents

Wang

Boyd

Hunter³

et al. 2018

International Journal of Pharmaceutics

Self Cite

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“…[274,275] In addition to localized drug delivery for antifungal or contraceptive purpose, the vaginal route is suitable for systemic administration of drugs due to its dense vasculature and avoidance of first-pass metabolism and enzymatic degradation of drugs associated with the oral route. [277,278] Compared to common intravaginal drug formulations such as tablets, gels, creams, and suppositories, vaginal rings allow sustained and long-term delivery of pharmaceutical substances, which can be controlled by the user and does not interfere with any sexual experiences. [277,278] Compared to common intravaginal drug formulations such as tablets, gels, creams, and suppositories, vaginal rings allow sustained and long-term delivery of pharmaceutical substances, which can be controlled by the user and does not interfere with any sexual experiences.…”

Section: Vaginal/intrauterine Deliverymentioning

confidence: 99%

Microfabricated Drug Delivery Devices: Design, Fabrication, and Applications

Zhang

Jackson

Chiao

2017

Adv Funct Materials

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Microfabrication technology has enabled the development of novel controlled-release devices that possess an integration of structural, mechanical, and perhaps electronic features, which may address challenges associated with conventional delivery systems. In this feature article, microfabricated devices are described in terms of materials, mechanical design, working principles, and fabrication methods, all of which are key features for production of multifunctional, highly effective drug delivery systems. In addition, the current status and future prospects of different types of microfabricated devices for controlled drug delivery are summarized and analyzed with an emphasis on various routes of administration including ocular, oral, transdermal, and implantable systems. It is likely that microfabrication technology will continue to offer new, alternative solutions to design advanced and sophisticated drug delivery devices that promise to significantly improve medical care.

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Pharmaceutical Approaches to HIV Treatment and Prevention

Yavuz

Morgan

Showalter

et al. 2018

Advanced Therapeutics

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Human immunodeficiency virus (HIV) infection continues to pose a major infectious disease threat worldwide. It is characterized by the depletion of CD4 + T cells, persistent immune activation, and increased susceptibility to secondary infections. Advances in the development of antiretroviral drugs and combination antiretroviral therapy have resulted in a remarkable reduction in HIV-associated morbidity and mortality. Antiretroviral therapy (ART) leads to effective suppression of HIV replication with partial recovery of host immune system and has successfully transformed HIV infection from a fatal disease to a chronic condition. Additionally, antiretroviral drugs have shown promise for prevention in HIV pre-exposure prophylaxis and treatment as prevention. However, ART is unable to cure HIV. Other limitations include drug-drug interactions, drug resistance, cytotoxic side effects, cost, and adherence. Alternative treatment options are being investigated to overcome these challenges including discovery of new molecules with increased anti-viral activity and development of easily administrable drug formulations. In light of the difficulties associated with current HIV treatment measures, and in the continuing absence of a cure, the prevention of new infections has also arisen as a prominent goal among efforts to curtail the worldwide HIV pandemic. In this review, the authors summarize currently available anti-HIV drugs and their combinations for treatment, new molecules under clinical development and prevention methods, and discuss drug delivery formats as well as associated challenges and alternative approaches for the future.

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Matrix and reservoir-type multipurpose vaginal rings for controlled release of dapivirine and levonorgestrel

Abstract: 19A matrix-type silicone elastomer vaginal ring providing 28-day continuous release of dapivirine

Cited by 42 publications

References 54 publications

Intravaginal rings for continuous low-dose administration of cervical ripening agents

Intravaginal rings for continuous low-dose administration of cervical ripening agents

Microfabricated Drug Delivery Devices: Design, Fabrication, and Applications

Pharmaceutical Approaches to HIV Treatment and Prevention

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