Delivered Dose Uniformity of Inhalation Powders. DPIs.

General information:

Dry Powder Inhalers (DPIs) are another type of inhalation drug delivery system, similar to Metered Dose Inhalers (MDIs). However, there are distinct differences in their operation and challenges in their testing:

1. Flow Resistance. DPIs offer varying degrees of resistance to flow. This means that different inhalers will require different levels of patient effort for inhalation. The inherent resistance in each DPI design stems from factors like device geometry, mouthpiece design, and powder properties. Therefore, the testing setup for DPIs should accommodate this variable resistance to mimic patient usage accurately.
2. Volume Setting. The integration of adjustable flow timings based on specific volumes, such as 2 or 4 litres, is crucial. This is because it helps simulate the inhalation volume of a typical patient. By setting the volume, testers can ensure the drug delivery during testing closely mimics the real-world usage of the DPI by patients.
3. Working airflow. For DPIs, the air flow rate is much higher than for MDIs (28,3; 60; 90
   L/min, ecc).
4. Sampling & Testing. Unless a specific monograph indicates otherwise, it’s standard to test the drug content from 10 separate units. This ensures consistency across multiple units of the same product. From each of these units, drug content determinations are made at two distinct stages: at the beginning of the unit’s lifespan and at the end. This ensures that the DPI provides a consistent dose throughout its entire life. As a result, from 10 separate units, a total of 20 determinations will be made (2 from each).

By conducting such rigorous testing on DPIs, manufacturers and regulatory bodies can ensure the consistency and efficacy of the drug delivery to the patient. DPIs’ unique challenges, like varying flow resistance, necessitate specialized testing protocols to ensure they meet the therapeutic needs they are designed for.

System:

There are important differences between Metered Dose Inhalers (MDIs) and Dry Powder Inhalers (DPIs), especially in how each device delivers the drug. DPIs rely on the patient’s inspiration, making it even more crucial to replicate real-world usage conditions during testing.
Just like with the MDIs, for DPIs, a timer-controlled, electrically operated two-way solenoid valve is essential. Positioned between the collection tube and the vacuum pump, this valve controls the airflow supplied to the inhaler during testing.
DPIs don’t use propellants and rely on the patient’s own inhalation to disperse the drug, it’s imperative to simulate this during testing accurately. This fundamental distinction mandates precise control over airflow in testing DPIs.
The manner in which DPIs aerosolize the drug is contingent upon the user’s inhalation strength and duration. A typical adult produces a pressure drop of approximately 4 kPa when inhaling, leading to the device’s flow resistance, combined with the patient’s inhalation, determines the flow rate. Once this typical flow rate is ascertained for a particular device, it’s used consistently across all tests for that device. The volume of air to be sampled during testing is set based on an average inhalation.
The Ph.Eur. considers a single inhalation to be about 4 litres, whereas the FDA and USP use 2 litres. Ensuring critical flow conditions is crucial for accurate testing. Sonic flow occurs when the
speed of the medium (in this case, air) passing through an orifice reaches the speed of sound, leading to specific, consistent flow dynamics. Maintaining these conditions during testing guarantees the results are replicable and consistent.
In essence, while MDIs and DPIs serve similar therapeutic purposes, their mechanisms of drug delivery are fundamentally different. This difference mandates unique testing conditions for each.

Dusa:

For DPIs, the key difference in the DUSA setup is the addition of a pressure tap.
DPIs function is based on the patient’s inhalation effort. This means the pressure drop caused by the patient’s inhalation, which in turn affects the dispersion of the drug, is a critical factor in its functioning. By introducing a pressure tap into the DUSA, this inhalation effort can be accurately simulated and measured during testing.
The pressure tap allows for the measurement of the pressure differential across the DPI. This provides insights into how the device will perform under actual usage conditions. As mentioned earlier, a typical adult produces a pressure drop of around 4 kPa when using a DPI.
The pressure tap can help in determining the flow rate across the device, which is a significant parameter when testing DPIs. This is because the drug’s aerosolization in DPIs is heavily dependent on the flow rate, which is dictated by the patient’s inhalation effort.

Procedure:

1. Flow Control Valve Adjustment. Adjust the flow-control valve to achieve a flow rate that causes a 4 kPa pressure drop across the DPI device being tested. This simulates the typical inhalation strength of an adult patient.
2. Volume Limitation. The volume of air sampled should not exceed 2.0 L, replicating a typical inhalation.
3. Test Flow Rate Determination. Set up the DDU sampling apparatus. Ensure an airtight seal between the product and the mouthpiece adapter. Monitor the pressure drop using a differential pressure transducer. Achieve and maintain a 4.0 kPa pressure drop across the product by adjusting the flow-control valve, ensuring critical (sonic) flow.
4. Flow Rate Measurement. After removing the DPI product, measure the flow rate drawn from the mouthpiece using a connected flowmeter. 
5. DPI Drug Release. Prepare the DPI according to its labeled instructions. With everything in place and the vacuum pump on, release the drug into the DDU apparatus. This is done by activating the timer-controlled solenoid valve which allows a 2.0 L volume of air to be drawn through the DPI at the pre-determined flow rate.
6. Assay & Analysis. After the drug has been released, detach the DPI from the DDU apparatus and disconnect the vacuum. Rinse the filter and the interior of the apparatus with a suitable solvent to ensure all of the drug is collected. Use a validated analytical method to determine the amount of drug released during the test and report the data both as the absolute amount delivered and as a percentage of the labeled claim.
   The filter and collection container/tube are designed to accommodate a larger 47-mm diameter filter.

The introduction of an integrated system by InPharmaTEC streamlines the testing process for inhalation products, such as MDIs and DPIs. By combining critical components—flowmeter, solenoid valve, timer, vacuum pump, differential pressure transducer, critical flow controller (for both, MDIs and DPIs), into one unit, the workflow is indeed simplified, reducing potential sources of error and enhancing efficiency.

Benefits:

1. Efficiency. By merging multiple components into a single unit, the setup and calibration time is likely reduced. This speeds up the entire testing process.
2. Accuracy. A single integrated unit reduces the potential for errors that might arise when connecting multiple separate devices.
3. Consistency. With an integrated system, every test is performed under identical conditions, ensuring consistent results.
4. Ease of Use. Operators only need to become familiar with one integrated device rather than multiple separate components, making training and daily use simpler.
   Space Saving. Combining multiple devices into one means a more compact footprint in the laboratory.

At TCR Tecora, InPharmaTEC, our dedication is unwavering towards our customers and patients with respiratory diseases. We recognize the unique challenges they face, and we’ve committed ourselves to deliver innovative and compassionate solutions that enhance their quality of life.
We have meticulously streamlined our processes to ensure that every moment counts, delivering efficient healthcare solutions that prioritize the well-being of those we serve.