Increase control, reduce costs with DissolvIt

  • 5 december, 2013
  • 15:52

DissolvIt – Inhalation Sciences’ in vitro simulation module – has been continuously enhanced over years of close collaboration with, amongst others, Astra Zeneca and GSK. Today it includes many unique features delivering major benefits to early-stage aerosol drug developers. Product development and in vitro studies manager Maria Börjel (Med Lic) takes us inside DissolvIt.

In a world of rapid technology and marketing hyperbole, the word ‘unique’ is often overused. But the benefits and features of DissolvIt, the in vitro simulation module of Inhalation Sciences’ PreciseInhale system, really are unique.

Since the first prototype in 2008 Inhalation Sciences’ founder and inventor Dr Per Gerde has transformed common preclinical R&D challenges into a range of unique new features, all delivering significant benefits to early stage inhalation drug developers. Developed through ongoing research projects with big pharma companies the new features include a single use cell, refined optical microscopy and a fully customized, flexible Fraction Collector.

The care, craft and attention to detail that has gone into developing these new features has produced a responsive, mature, world-class technology.

Milligrams not grams, rank and eliminate drug candidates early on
DissolvIt delivers reliable, highly cost-effective data on both the absorption and dissolution of inhaled materials using extremely small amounts – milligrams not grams – of test substance.
It allows pre-clinical inhalation drug developers to eliminate drug candidates early on in the research process, and rank drug candidates.

“Every single part of DissolvIt has been developed, piece by piece, in response to real challenges we faced with clients in the lab. The module has been optimized and improved in so many ways. It’s been my baby,” says Inhalation Sciences’ product development and in vitro studies manger Maria Börjel, who has been involved with DissolvIt since the beginning. So what are the other unique benefits of DissolvIt?

Increased range, reduced does: Up to nine cover slips
With a highly customizable computer interface steering it, the PreciseInhale aerosol generator can carry out simultaneous exposures of up to 9 cover slips, or glasses, using extremely low amounts of test substance (typically <50 mg.) This makes DissolvIt extremely cost-effective. Delivering accurate results with low standard deviation for up to nine doses helps researchers eliminate non-viable drug candidates early on in the development process. Optical microscopy and absorption: Early indications and results you can really see
Optical microscopy is another unique DissolvIt feature enabling the elimination of nonviable candidates early on. Optical measurement provides an effective early indication of the absorption/dissolution process that can then be verified and explored with the full data.
Maria Börjel: “DissolvIt monitors absorption as well as dissolution of the test substance. The optical tool monitors absorption. With DissolvIt the particles are brought into contact with the artificial air blood barrier and studied from the ‘luminal’ side through optical microscopy. The optical display means you can actually see the particles, and measure the spread of them and how quickly they are absorbed by the artificial lung lining. We take pictures of the substances absorbing into the simulated lung mucus, reproduced using lipids and polyethylene oxide.”

Single use cell: More reliable simulation of dissolution
DissolvIt has been refined and optimized by Dr Gerde and the team over the years, with the core of the module, the single use cell, perfected in 2010. “It makes the system much more reliable and easier for the operator to handle,” says Maria Börjel.

The blood in this artificial air-blood barrier is simulated with a phosphate buffer including albumin, with a pH level of 7.4, the natural pH level of blood. In this way the dissolution of the powder into the blood is mimicked. Together with lipids in the gel and albumin in the buffer, the realism of the dissolution is ensured.

“DissolvIt mimics the results of organic aerosol tests really well,” says Börjel. “For Astra Zeneca, for example, the substances were able to distinguish from each other, and the dissolution profiles reflected the characteristics of the substances well. For early research this is an effective simulation – you can see if it is a fast or slow dissolution, and the system allows you to rank and eliminate substances early on.”

Fully programmable and customizable Fraction Collector
Finally the perfusate is collected into another unique feature for DissolvIt, the module’s fully customizable Fraction Collector. A major limitation for existing fraction collectors is their inflexibility. Inhalations Sciences’ Fraction Collector collects 96 well plates and is fully customizable and programmable.
Maria Börjel: “The custom-made and programmable Fraction Collector is a brilliant development. A big limitation for fraction collectors is you can’t program them – with ours you can choose to collect fractions over different time periods with drain periods of different lengths in between. You can program and design your own program for the fraction collector. For clients the added flexibility, like so much about DissolvIt, means more detailed, specific data.”

Responsive, resourceful, multi-disciplinary: The Inhalations Sciences Team
So what kind of team is it that has so ingeniously and responsively customized and created new features from their clinic and client experience? Maria Börjel emphasizes the receptiveness, profound communication skills and sheer ingenuity of Inhalation Sciences’ founder and technological inventor, Dr Per Gerde, plus the strong multi-disciplinary range of a small team with broad reach and great knowledge.
“All three scientists in the Inhalation Sciences’ team really appreciate Per as an inventor. He is a problem-solver of tremendous resourcefulness. It is so good to have him to speak to in the lab. Communication is so easy with him – we find things out and realize things that need to be developed, he listens, and then he comes up with the technical know-how, I don’t know how he does it, he just knows how to solve these problems.”
For a team developing highly sophisticated medtech equipment of this type, says Börjel, state-of-the-art engineering, as well as chemical, medical, pharmacological and pharmacokinetic skills are all essential. Börjel stresses that the team at Inhalation Sciences’ is truly multi-disciplinary, with each member bringing a strong skill-set to the group.
“My background is as a civil engineer in biotechnology; my thesis was in cancer research and signaling pathways in cell cultures. Fernando is a chemist and Ewa, our IPL expert is a medical doctor. Together we cover all the skills, we learn from each other all the time. This is a small company that works closely and cooperatively and that pools a huge amount of expertise. Inhalation Sciences is a multi-skilled company that can respond to and understand the needs of any aerosol research team they work with. We are stronger and more coherent because of our diversity. We learn and work together. The skills and experiences of these four scientists really enrich the company.”