Improved Stability and Efficacy of Drugs through Nanoformulation

By AZoNano

Table of Contents

Introduction

Nanoformulation enables the sheathing of drug particles with polymeric surfactants, which can then be layered onto a substrate for future delivery. Annually as much as $40 billion is invested in drug discovery. However, many of the resulting potential drugs display poor water solubility and an inability to deliver therapeutic agents in vivo. It has been estimated that just 40 to 50% of these chemical entities are water soluble, causing inefficiency in the R&D process. Because of the challenges of assessing efficacy in biological models for a poor bio-available compound these compounds are shelved with no further development activity even if they display promising therapeutic activity in cell culture. This problem can be addressed by nanoformulation, drastically enhancing bioavailability, water solubility, efficiency and effectiveness.

Unique Features of Nanocopoeia’s ElectroNanospray™ Process

Other nanoformulation techniques use top-down, multi-step methods like homogenization or wet milling to create nanoparticles. The issue with these is that both need secondary processing for creating a monodisperse range of particle size. The ElectroNanospray™ (ENS) process constantly creates bare or coated drug nanoparticles i.e shell nanoparticles in a single bottom up processing step. Furthermore ENS-produced drug formulations can produce coated nanoparticles in a single processing step.

Technique by Which ENS Collects Dosage Form of Nanoformulated Drug Compounds

Multiple techniques have been optimized by Nanocopoeia to accomplish this. One technique involves spraying the nanoparticles directly into a liquid. Another involves collecting them in a dry form on a substrate for suspending again in a liquid at a later point of time. A dry, convenient shelf-stable format ideal for sterile delivery into biological models is obtained by the second method. It has also resulted in considerably improved drug solubility or nano-suspendability.

The ElectroNanospray Process

The above approach has been used to improve solubility for three poorly water-soluble drugs:

• griseofulvin, an antifungal
• nifedipine, a calcium-channel blocker
• carbamazepine, an anticonvulsant.

All three are drugs that have been well-established in clinical practice, but have very low to non-detectible solubility in water, making them ideal model compounds for development using the ENS process.

The process is detailed below:

1. With the help of the coaxial 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, which is compatible with the drug material. This solvent can be a conventional solvent that would not be acceptable or usable in a biological system since the solvent flashes off as a result of the production process, leaving nanoparticles with no solvent component.
3. When the material stream disintegrates into nanoparticles by applying an electric current, each discrete particle has an enormous surface-area-to-volume characteristic. Due to 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 determined 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 mm pore size (1,000 nm) nylon filter, and a filtrate of this material was passed through a 0.2 mm (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 8 shows the improvement in solubility i.e suspendability over the raw drug powder.

Conclusion

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 specific benefit 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.

About Nanocopoeia

Built on a foundation of revolutionary intellectual property, Nanocopoeia has grown into a major nanotechnology player in just 10 years. With beginnings at the University of Minnesota dating back to 2001, the company formally began operations in late 2003 after obtaining worldwide exclusive rights to the patent portfolio developed by Drs. David Pui and Da-Ren Chen. The core patents obtained from the University of Minnesota cover the use of ElectroNanospray™ to create nanoparticles out of virtually any material that can be put into solution or suspension. That patent estate has undergone continual updating and enhancing to broaden Nanocopoeia's claims both through the University and by the company during its operation.

This information has been sourced, reviewed and adapted from materials provided by Nanocopoeia.

For more information on this source, please visit Nanocopoeia.