Dose counting

Pulmonary drug delivery is considered the preferred route of delivery for a range of drugs for both local and systemic treatment. This is because local treatments remain the most effective for the management of respiratory diseases such as Asthma and COPD and the lungs provide a large surface area for deposition and drug absorption as well as a rapid onset of action. Moreover, the administration of drugs through the lungs allows the dispensing of small drug doses which are clinically effective and thus provide less systemic side effects. This route is also considered non-invasive when compared to injections; it is well tolerated and accepted by most patients, thus increasing patient compliance.

There are three main types of devices commonly to deliver drugs to the lungs:

• pressurized Metered Dose Inhalers (pMDIs)
• Dry Powder Inhalers (DPIs)
• Nebulizers

Pressurized Metered Dose Inhalers have been available for over 50 years and have come to be regarded as the preferred form of delivery for many drugs for treatment Asthma and COPD with nearly 500 million devices manufactured world-wide each year. pMDIs offer a unique combination of reliability, accurate dosing, convenience and low cost for delivering drugs to the lungs.

Despite all of these benefits, pMDIs still have a major disadvantage over other dosage forms-they offer no convenient way for patients to accurately track their doses.

In March 2003, the Food & Drug Administration issued guidance for the industry on the subject of integrating dose-counting mechanisms into pMDI drug products. This guidance specifically refers to orally inhaled pMDI drug products currently under development. The key points from this guidance can be summarised as follows:

• Dose counter means both mechanisms: numeric count or dose-indicating;
• Dose counter must be an integral part of the MDI canister and/or actuator and not an add-on;
• Dose counter must provide a clear indication when approaching and when reaching or exceeding the end;
• Counts downward ;
• Designed to specifically avoid undercounting;
• Reliable;
• Ergonomics, ruggedness, accuracy of the counter to be tested in clinical settings (including pediatrics, geriatrics);
• No lock-out (for bronchodilators).

In response to this industry trend, Valois has developed the Landmark technology, a p-MDI indicator designed to be integrated as part of the p-MDI actuator. The Landmark technology is based on a mechanical counting system triggered by the displacement of the metering valve. This system was engineered so that undercounting is very specifically avoided. Its robustness has been carefully evaluated through the performance of rigorous stress tests such as transportation simulation, inadvertent drop, temperature cycling, etc...

The counter itself is made out of 4 parts only and remains compact so that it can be easily integrated within standard MDI actuators of various sizes and shapes. It is positioned outside the actuator sleeve so that interference with the airflow inside the MDI actuator remains negligible. This feature is very important when a counter needs to be added to an existing product or to a product that is developed at an advanced stage. A significant modification of the airflow path in a metered dose inhaler could lead to altered pharmaceutical performance (e.g. content uniformity or aerodynamic particle size distribution). This could therefore lead to having to conduct additional in vitro or in vivo studies to demonstrate equivalence.

Landmark offers a combination of numeric and colour high visibility display so that the amount of product left in the canister can be visualized easily and quickly by patients. This display was evaluated during a specifically designed user test involving patients and healthcare professionals. The overall feedback from this test was very positive.