New device may stop HIV infections in women

A new medical device that works inside a woman's body to release an anti-retroviral drug already taken by 3.5 million HIV-infected patients worldwide has shown to be 100 percent successful in stopping the transmission of the simian immunodeficiency virus in primates.

A new trial will begin on human females in hopes of finding a relatively easy solution to the scourge of HIV/AIDS. The new ring is easily inserted and stays in place for 30 days. And because it is delivered at the site of transmission, the ring – known as a TDF-IVR (tenofovir disoproxil fumarate intravaginal ring) – utilises a smaller dose than pills.

What's the Big Idea?
The vaginal route of administration offers a promising option for local and systemic delivery of drugs. Vaginal ring devices (also known as Intravaginal Rings and V rings) are already commonly used for contraception and hormone replacement therapy but the potential for exploiting vaginal ring technology for the prolonged delivery of HIV microbicides.

Because current pill regimes of anti-retroviral therapies must be taken in large quantities several times per day, compliance rates are not what doctors would wish. The same goes for anti-retroviral gels to be applied before sexual contact. But the ring's strength stems from its unique polymer construction: its elastomer swells in the presence of fluid, delivering up to 1,000 times more of the drug than current intravaginal ring technology. Other drugs could potentially be integrated into the ring, such as contraceptives or antiviral drugs to prevent other sexually transmitted infections – a feature that could increase user rates. 

The development of an effective HIV microbicide could play an important role in preventing women becoming infected with the virus by preventing or decreasing the likelihood of viral transmission and subsequent infection.  In turn, a microbicidal vaginal ring would essentially replace conventional poorly retentive semi-solid formulations and place a woman in greater control of her own sexual health which would have a significant impact on HIV transmission rates amongst the poorest women in the developing world.

What’s the testing solution? 
There is the possibility that inclusion of excipients into Intravaginal Ring formulations may adversely influence their mechanical properties. The mechanical properties of an IVR must ensure optimal vaginal compatibility and user acceptability.

If the mechanical strength is too low, the ring could either be expelled from the vagina or be prone to rupture. If the mechanical strength is too high, the inflexibility of the device could cause irritation/ulceration of the vaginal tissue.

It is therefore necessary to assess the mechanical characteristics of the rings before and after release, since both incorporation of such excipients into the rings and the subsequent release/uptake of drug/excipients/release medium are likely to influence their mechanical characteristics. 

The compressional strength of each formulation can be evaluated on a Texture Analyser.  Compressional force required to depress the vaginal rings through a specified distance is measured. The ring is placed vertically in a holder and subjected to a compression cycle to a distance of 5mm, at a rate of 2mm/s for 5 cycle counts using an aluminium probe. The rings are tested before and after the 4-week dissolution period. Any further physical modifications to the ring design, such as core length or sheath thickness, would also need to be assessed to investigate any potential compromise on the mechanical properties.

Published paper

'Intravaginal ring delivery of the reverse transcriptase inhibitor TMC 120 as an HIV microbicide' is a paper published (International Journal of Pharmaceutics 325 (2006), 82-89) by researchers at Queen’s University, Belfast, where this delivery means was first considered and researched. 

Other medical device breakthroughs at Queen’s

'A proposed model membrane and test method for microneedle insertion studies' has been published by researchers at Queen's University, Belfast.

Microneedle (MN) devices are composed of an array of micron-size needles. These systems are currently attracting great interest in transdermal drug delivery research. MN has the ability to pierce the outermost layer of the skin, the stratum corneum, and create micro-conduits that can deliver drugs to the deeper layers of the skin, from where they can be absorbed directly into the systemic circulation. Several key physical factors affect MN performance: type of material, needle height, tip-radius, base diameter, needle geometry and needle density. The penetration depth and the fracture force of MN are determined by all these factors.

Clearly, effective penetration of MN arrays into the skin is the primary pre-requisite for effective drug delivery. However, when developing and testing MN systems, it is apparent that there are limited techniques to evaluate this aspect. This paper uses humans and the TA.XTplus texture analyser for insertion of microneedles and, in doing so, proposes an insertion test that can be easily implemented as a routine method to compare MN formulations and to control the quality of MN arrays. This can be of value in scaled-up MN production processes.

The test proposed in this study can be used to complement existing techniques for the physical characterisation of MN arrays. The key aspects are the identification of PF as a suitable skin simulant for MN insertion and the development of a facile, rapid and reliable insertion test, with potential for use as a QC test method, or for comparative formulation studies: http://bit.ly/1kJZhP5

---

We can design and manufacture probes or fixtures for the TA.XTplus texture analyser that are bespoke to your sample and its specific measurement.

Once your measurement is performed, our expertise in its graphical interpretation is unparalleled. Not only can we develop the most suitable and accurate method for the testing of your sample, but we can also prepare analysis procedures that obtain the desired parameters from your curve and drop them into a spreadsheet or report designed around your requirements.

For more information on how to measure texture, please visit the Texture Analysis Properties section on our website.

The TA.XTplus texture analyser is part of a family of texture analysis instruments and equipment from Stable Micro Systems. An extensive portfolio of specialist attachments is available to measure and analyse the textural properties of a huge range of food products. Our technical experts can also custom design instrument fixtures according to individual specifications.

No-one understands texture analysis like we do!

To discuss your specific test requirements click here...