The combination of an aging global population and increased urban pollution levels has led to a significant increase in the prevalence of asthma. It has been estimated that 300 million people suffer from the conditional globally, and that poor disease control causes approximately 250,000 deaths per year. Given the impact the disease has, especially within poorer communities, the recent message from the Global Initiative for Asthma (GINA) on World Asthma Day suggested that it was ‘Time to control asthma’.

Time for controlOne of the barriers to asthma control identified by GINA is the high cost of medications. The complexity of inhaler devices and formulations, especially those based around dry powders, provides a significant barrier to generic competition and therefore keeps costs high. In response to this, the US FDA is sponsoring studies aimed at understanding the effectiveness of dry powder inhaler products, and has issued new product-specific bioequivalence guidance describing how bioequivalence may be established between a generic and Reference Listed Drug (RLD) product.

In developing a generic Dry Powder Inhaler (DPI) device, the following aspects of the product need to be considered:

  • DPI device design: the device should operate in a similar way to the RLD product, such that a patient can easy transfer to it. In addition, the device resistance to air flow should be similar, as this important in defining the energy input into the powder to achieve dispersion during patient use.
  • DPI formulation: the dose level, efficiency of device emptying and the degree of dispersion of the dose during inhalation by the patent should be the same as the RLD, as these define how much drug deposits with the target region of the patient’s airways.
  • Patient factors: this includes considering the flow rate a patient may be able to achieve through the device during inhalation, as this may affect drug dispersion.
Spraytec Inhaler and Nebulizer Accessory

Spraytec Inhaler and Nebulizer Accessory

The Malvern Spraytec laser diffraction particle sizing system can provide a significant aid to formulators in understanding the processes of powder entrainment, dispersion and delivery during the actuation of a dry powder inhaler. By measuring the powder size distribution in real time during device actuations, the system enables researchers can gain insight into how adjustments in a formulation can affect drug delivery . It is also possible to quickly screen how changes in the flow rate applied to a device changes the degree of dispersion achieved. This may help in comparing the performance of a generic product to the RLD or in understanding how a device may operate for different patient groups.

Although Spraytec can be used to understand the dispersion processes which occur during dry powder inhaler use, it does not provide specific data relating to the drug substance.  Obtaining component-specific data can aid the process of deformulation, especially when developing combination therapies containing more than one active. Here, the Morphologi G3-ID can be used in combination with traditional cascade impaction methods to obtain particle size and shape data for each formulation component. This enables more precise comparisons to be made of the degree of drug dispersion achieved when assessing bioequivalence. Used with Spraytec, this can deliver the knowledge required to achieve product control.

Resources

Download the Spraytec article: “Aerosolization Analysis – Unlocking the Secrets of the Dry Powder Inhaler Plume

Download the Morphologi G3-ID application note: “Component specific particle characterisation of dry powder inhaler formulations”.

Download the following article to learn how Spraytec and Morphologi G3 can be used together to understand DPI performance: “Laser diffraction and automated imaging: complementary techniques for dry-powder inhaler development.”

Previous Posts on Reverse Engineering:

“To BE or not to BE” – Bio-equivalence strategies for topical formulations

Viva la “sameness” – generic drugs and ensuring equivalence