Customer study for Bespak's AFT system

A recent AFT study was to identify the most suitable formulation and container closure system to carry through to early phase development.

A customer required that the product should deliver consistent doses through life and also that the system should eliminate the need for repriming. Repriming is required when a pMDI valve is left for a period of time and the metering chamber empties back into the can. The user of the pMDI will then experience an incomplete dose when they operate the pMDI and this is part of the reason why many inhaleable medicines require two or three puffs to deliver a complete dose.

Several possible formulations and container closure system options were identified. The formulation options were prepared and a physicochemical study was performed, figures 1-4.

The study identified two formulations that were suitable to perform the container closure compatibility study on. These were then manufactured by pressure filling into a standard aluminium can with a Bespak BK357 valve and a Bespak Easifill valve. With both valves two elastomer variants were tested.

The compatibility study demonstrated that all of the Container Closure System (CCS) options gave acceptable degradation profiles and so it was recommended that both formulations were taken through to the next stage with both the BK357 and Easifill valve variants using both elastomers.

During the next stage of the AFT study the formulation/ CCS options were subjected to through-life dose content uniformity testing, content assay and loss of prime testing. The data demonstrated that the Easifill valve design using two elastomers gave the most consistent dose content uniformity through life and that it eliminated the need for repriming, figure 5.

It was recommended that this option be carried through into short term stability testing using both elastomers. The stability study was conducted at initial and one month time points at 25°C/ 60% Relative Humidity (RH) upright and 40°C/ 75% RH inverted. The following tests were performed:

• through-life dose content uniformity;

• content assay; and

• loss of prime.

The short term stability testing showed that at accelerated conditions the pharmaceutical performance of both the CCS options was satisfactory, figure 6. The study concluded that one option was most suited to carry through to the next stage of the development with the Easifill valve and either of the two elastomer options.