Drug Formulations

Nanoformulation allows drug particles to be sheathed with polymeric surfactants, then layered onto a substrate for future delivery.

Improving Effectiveness, Extending Shelf Life

How does nanoformulation address today's drug formulation challenges?

In a word: bioavailability. As much as $40 billion is invested annually in drug discovery. Unfortunately, many of the drug leads that result exhibit poor water solubility and an inability to deliver therapeutic agents in vivo. In fact, it's estimated that 40-50 percent of these new chemical entities are poorly water soluble.

The result is inefficiency in the R&D process. Due to the challenges of evaluating efficacy in biologic models for a poorly bioavailable compound, these compounds are often shelved with no further development activity—even if they show promising therapeutic activity in cell culture. Nanoformulation addresses this problem by increasing surface area—dramatically improving water solubility, bioavailability, effectiveness and efficiency.

How does Nanocopoeia's ENS differ from other nanoformulation processes on the market?

Other nanoformulation processes use multi-step, "top-down" methods like wet milling or homogenization to create nanoparticles. The problem with these techniques is that both require secondary processing to create a monodisperse range of particle size. Nanocopoeia's ENS process consistently creates either bare drug nanoparticles or coated, core:shell nanoparticles in a single, "bottom up" processing step. In addition, ENS-produced drug formulations can produce coated nanoparticles in that single processing step.

How does the ENS process collect a dosage form of the nanoformulated drug compounds?

Nanocopoeia has optimized multiple techniques to accomplish this. One example is to spray the nanoparticles directly into a liquid. Another is to collect them in dry form on a substrate for re-suspension in liquid at a later time. The second method produces a convenient, dry, shelf-stable format ideal for sterile delivery into biological models. It has also resulted in significantly improved drug solubility (nano-suspendability).


How does the ENS process work in practice?

The above approach has been used to enhance solubility for three poorly water-soluble drugs: griseofulvin, an antifungal; nifedipine, a calcium-channel blocker; and carbamazepine, an anticonvulsant. All three are well-established drugs in clinical practice, but have very low to non-detectible solubility in water, making them ideal model compounds for development using the ENS process. Here's how it worked:

  1. Using the  spray nozzle, a solution of each drug in the relevant solvent system (e.g. alcohol, acetone, tetrahydrofuran) was co-sprayed with solvent and various surfactant materials, including those listed above. The substrate was a thin film of polyvinyl alcohol or stainless steel.
  2. The drug compound input for the ENS process is dissolved into a solvent system compatible with the drug material. This solvent can be a traditional solvent that would not be acceptable or usable in a biological system because the solvent flashes off as a result of the production process, leaving nanoparticles with no solvent component.
  3. When the electric field causes the material stream to break into nanoparticles, each discrete particle has an enormous surface-area-to-volume characteristic. Because of this surface area, rapid solvent evaporation occurs, enabling the drug and surfactant materials to be deposited in dry form onto the substrate.
  4. Concentration of drug in phosphate-buffered saline was measured in three ways: In the "neat" suspension made when the dry film was placed into buffer, a filtrate of this material was passed through a 1 µm pore size (1,000 nm) nylon filter, and a filtrate of this material was passed through a 0.2 µm (200 nm) nylon filter typically used for performing sterile filtration of culture medium.
  5. Evaluation using two different measurement systems (of spray stream and in liquid) yielded particle sizes of approximately 60 nm. Figure 5 shows the improvement in solubility (suspendability) over the raw drug powder.

Water solubility for catalogue sourced drug powder versus nanoformulated drug prepared using ENS process

This approach has proven to be robust, with similar results obtained for other single and combination surfactant systems. The dissolvable film substrate is convenient, but not essential to obtain the improvements. A particular advantage of the ElectroNanospray process is the ability to work with very small quantities of expensive research-grade materials that the compounding pharmacists can make of these materials.

How can I work with Nanocopoeia?

Nanocopoeia is targeting commercial activity in drug discovery and development as a formulation resource for industry and academic researchers. We can work with you to create an efficient and effective way to leverage existing libraries of compounds with known solubility issues but with great commercial potential. Our particle design and rapid nanoformulation prototyping services are unique in the industry.