The dissolution profile of inhaled drugs underpins therapeutic efficacy and is an area of increasing regulatory scrutiny, particularly for the demonstration of bioequivalence in a generic. The new IDDC works efficiently with standard inhaler test equipment to reproducibly capture a representative sample for dissolution testing by US Pharmacopoeia (USP) Method 2, an apparatus routinely used for tablets.
Following deposition, inhaled drug particles must dissolve and permeate into the lung tissue to reach their site of action. Dissolution testing elucidates this behaviour and is particularly important for modified release or low solubility compounds, or when establishing parity between a test (generic) and reference (innovator) product. Currently published dissolution methods offer limited flexibility with respect to the particle size ranges analysed, tend to suffer from poor reproducibility and have low discriminating power. Inconsistent sample collection is a common problem.
The new IDDC accommodates a range of inlet components routinely used to measure the aerodynamic particle size distribution (APSD) of OIPs by cascade impaction including the standard USP induction port, the Next Generation Impactor pre-separator, the Fast Screening Impactor housing/insert and the Albert Idealised Throat. Choice of inlet component determines the particle size range captured for dissolution testing. This can be the Impactor Sized Mass (ISM - the mass that would penetrate the first stage of the impactor), the ex-throat dose or the Fine Particle Dose (FPD); the fraction of the dose defined as respirable on the basis of size. The dose is collected on a detachable insert, positioned inside a removable filter holder, at a test flow rate in the range 30 to 100 L/min, depending on the MDI or DPI under test. This insert can be directly transferred to a USP Method 2 apparatus for dissolution testing, similar to the established Paddle over Disc method (USP Method 5).
Because particles collect evenly across the surface of the IDDC insert, dissolution results are reproducible and independent of loading. Once a test is complete the insert is simply replaced for the next test. All wetted parts are manufactured from stainless steel ensuring durable compatibility with the widest range of dissolution media/simulated lung fluids. Without an inlet component fitted the unit has a diameter of 200mm and a height of 270 mm, occupying minimal lab space. In combination these features make the IDDC a practical and efficient tool for those looking to apply dissolution testing in the development of new and generic OIPs.