Addressing the Drug Solubility Issue

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Addressing the Drug Solubility Issue

Aesica LogoIncreasingly, we see poorly soluble compounds coming to us from customers, notes Aesica, a company at the forefront of the development and commercialization of new technologies and techniques.

In fact, says the company, it’s been a point of competitive differentiation to mark ourselves out from our competitors; we literally treat every new challenge with a bespoke solution. We’ve always taken a reversed engineered approach and begin by asking ourselves whether a solution or an approach is going to be commercially viable for our customers. The other aspect we focus on with all customers is how quickly we can undertake the development work; we want to enable them to reach their key milestones.

On a practical level, this means that we examine the science and chemistry of each candidate as a starting point. The experienced team at Aesica will first look at a compound’s properties and chemistry, such as whether it is hydrophobic or lipophilic, and examine whether we can find an excipient that might be able to help improve the API’s availability when formulated. For example, cyclodextrin, which works with all hydrophobic compounds and can be used with longer chain molecules, lipidic excipients for lipophilic APIs (such as Maisine 35-1

[Oily Vehicle] or Gelucire 44/14 are two prime examples) and solvents such as Transcutol are powerful solubilizers.

Once we have established our ingredients as a base, Aesica then has a range of specialist technologies available that can be used to help to increase the surface area of compounds or alter their priorities to increase stability. The key point to stress here is that when we work with customers, we also use scalable technologies; we initially start on a very small scale to preserve as much as possible of the customer’s valuable APIs, helping to reduce costs.

Scalable Solutions
With such growth across this market, being able to provide scalable solutions and work with the customer to develop a viable formulation helps us to achieve strategic partnership status and bring products to market that other CMOs can’t. One of our key technologies across our portfolio includes spray drying, which produces a dry powder from a liquid/slurry, thus increasing solubility. Wet bead milling is also another established technique for the production of submicron and nanosuspensions (nanomilling) and is used as a convenient and cost-effective method of enhancing bioavailability.

A fast growing technology, which we are developing, is hot melt extrusion, a technology that has actually been around for decades in other forms of engineering, but is still under used in pharmaceuticals. This process increases solubility by melting polymers and drugs together, and we are heading towards commercialization with one partner already. But the crucial benefit of this technology is that it is a largely continuous process — which means, again, that it uses only minimal API, but also removes the batch validations required during scale-up, meaning we can help expedite time to market.

Technologies and Trends
In fact, the hot melt extrusion process is a really good example of how we have looked at the trends in the market and sought out new technologies. We have working partnerships with local institutions that have early formulation expertise, where we can provide the know-how to upscale the product for clinical manufacture. As a business, we are constantly searching out new technologies — presuming that they are going to be commercially viable — and we currently have several more very promising technologies in the pipeline. This is a crucial point as a CDMO and the ability to implement these types of solutions moving forward is really going to be a major differentiator. It is something we have invested heavily in and are now starting to reap the rewards from, as we see such a rise in customers with these types of problems.

The reason that so many new innovative compounds tend to be poorly soluble is, quite simply, because most of the easier formulations have already been created. Less than 10% of new candidates have high solubility and permeability. Secondly, we are actually now seeing a lot of companies revisiting existing compounds from 5, 10 or even 15 years ago. The belief is that with new technologies and approaches on offer, these compounds are now viable for commercialization.

We are really well set in the market within this area and are quite comfortable with customers bringing new challenges forward. And we would actively seek out and invest in new technologies for a customer with a prospective product that they have so far been unable to solve.