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Improving Bioavailability & Solubility: Chemical & Physical Modification vs. Formulation Development

Pharmaceutical scientists are always looking for ways to solve bioavailability and solubility issues related to delivering therapeutic payloads on target, on dose, and on schedule. Within the bounds of oral-solid dose forms, bioavailability and solubility issues are still resolved through a tried and tested set of formulation tools.

“However, although oral delivery for a broad range of APIs is well anticipated by popular non-proprietary methodologies, standard off-the-shelf solutions may not be enough for more challenging APIs,” says Robert Lee, PhD, President, Particle Sciences. “Without exploring alternative, more specialized formulation techniques, these actives may not progress through the development pipeline.”

Finding an effective method to dose more complex molecules may be less straightforward, but techniques do exist to successfully incorporate these actives into viable drug products. It is important to assess a range of technologies, ideally orthogonal, to address the molecule-specific challenges that become apparent during pre-formulation. Armed with the proper knowledge and tools, formulation scientists can narrow down the potential approaches to find a strategy that may maximize the delivery of poorly soluble drugs, and at the same time, achieve other drug product critical quality attributes, says Dr. Lee.

For example, Particle Sciences’ LyoCell® in-licensed technology combines a lipid-based approach with nanoparticles while leveraging reverse cubic-phase matrix. “This assures that the hydrophobic and hydrophilic domains in these nanoparticles are never more than a few nanometers apart and may lead to unique solubilization properties,” he says. LyoCell Technology uses GRAS ingredients and is intended for a range of applications and every route of administration.

In some cases, formulation and delivery methods alone may not be enough and it may be appropriate to modify the API. “For example, make it into a prodrug that could then be hydrolyzed into the corresponding active that delivers the desired biologic performance,” he explains. “This approach can create a defensible basis for intellectual property that may provide a drug developer a suitably viable and less risky approach.”

In the vast majority of cases, formulation and delivery technologies do provide an effective means to the therapeutic ends that Particle Sciences’ customers are seeking. “But it doesn’t work in every case,” Dr. Lee admits. “You have to have an open mind and do what the molecule requires to be formulated; be it formulation or chemical modification to successfully deliver the molecule and achieve the desired target product profile.”

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