Factors influencing inhaled product development


Factors influencing inhaled product development - Image




The quality of an inhalable formulation is judged on three key properties:

- Emitted Dose (ED): the amount of formulation which leaves the inhaler/device
- Fine Particle Fraction (FPF): the percentage of drug which reaches and stays in the lung
- Bioavailability: the proportion of drug which reaches the bloodstream and has a medicinal effect

All three factors can be influenced by the properties of an API particle. For the ideal inhaled medicine, all of the API would leave the device (100 % ED), and each particle would be between 1 - 5 µm to achieve the highest FPF (too large and the drug will not reach the deep lung, too small and it will be exhaled). This in turn will result in the highest bioavailability possible (more API reaches the bloodstream relative to dosage size).

In conventional ‘top-down’ drug development, considerable effort is expended in making non-ideal API particles effectively respirable. From micronisation to reduce particle size and the addition of excipients to counter the negative effects of mechanical milling, the result is often product losses, errors, increased processing time and cost, as well as decreasing the relative amount of API in the final product.

Single step, ‘bottom-up’ processes such as Crystec’s mSAS® (modified Supercritical Anti-Solvent) platform, which generate powders directly from solution, can produce API particles with ideal properties for inhalation and offer huge advantages. Particles have smooth, low energy surfaces, creating free flowing powders with good aerodynamic properties, enabling a high ED. Particles can be tuned to the ideal particle size for inhaled delivery, enabling a high FPF. Pure inhalable API particles can be delivered to the lung (without the need for carriers e.g. lactose) efficiently, requiring simple inhaler devices, and in small, less frequent doses.

Below is an SEM image of an mSAS®-processed material, grown from solution in a single step, and its particle size distribution data.

ACI

Scanning Electron Microscope (SEM) image and Symatec particle size measurements of mSAS® inhalation product

To learn more about Crystec's inhaled product development, please see our case study detailing how mSAS®  can be applied to enable inhaled delivery of a previously orally administered drug. Our video also demonstrates the influence of aerodynamic performance on lung delivery. Alternatively, get in touch!