Dissolution Testing For Inhaled drugs - Pharmaceutical Technology

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Dissolution Testing For Inhaled drugs
Although there are no regulatory requirements or established pharmacopoeial techniques for the dissolution testing of inhaled drugs, such testing can potentially open up the opportunity to tailor formulation properties. The authors explain how a new technique using standard dissolution test equipment in combination with US Pharmacopeia methods for the dissolution testing of solid dosage forms can be used to differentiate the solubility of orally inhaled products.

Pharmaceutical Technology Europe
Volume 22, Issue 11

Assessing different dissolution media

Figure 5: Dissolution profiles for budesonide measured using different dissolution media: phosphate buffer, simulated lung fluid (SLF) and phosphate buffered saline (PBS).
In the first instance, dissolution profiles for BD were measured using three solvents: simulated lung fluid (SLF); 0.2M phosphate buffer (pH 7.4); and phosphate buffered saline (PBS) (Figure 5). There are currently no pharmacopoeial suggested components for artificial lung fluid and it is not feasible to exactly mimic conditions in the lung; rather, the aim during this phase of the study was to identify an appropriate, practical fluid that would simplify testing within the constraint of maintaining relevance.

The concept of SLF was introduced by Moss and the solution is described as being similar to actual lung fluid in terms of ionic composition and pH, the full composition can be found at the original reference.6 Unfortunately SLF has low pH buffering capacity and its pH varies significantly with time (over a 24 h period) unless carbon dioxide is continuously bubbled through. There was a possibility that a flow through system might theoretically help to alleviate the issue of low pH buffering capacity, but at the time of the experiments this speculation was wholly unproven. Therefore, the other dissolution media assessed were considered to be a more practical choice, especially for pH-sensitive or slowly dissolving formulations.

For the assessment of different dissolution media, the DPI was fired just once during each sample collection. The similarity factors for PBS and phosphate buffer are 63.4 and 56.1, respectively, compared with SLF suggesting that either is a suitable substitute.

Figure 6: Dissolution profiles for budesonide measured using surfactant-modified dissolution media. (DPPC is dipalmitoylphosphatidylcholine).
To address the issue of poor wettability with the hydrophobic BD, further trials were carried out, incorporating surfactant into the dissolution media. The results for two modified PBS solutions are shown in Figure 6: mPBS contains dipalmitoylphosphatidylcholine (DPPC), tPBS contains polysorbate 80. DPPC is one of the main components of lung surfactant and lowers surface tension at the air–water interface by forming a monolayer. Here, however, the results suggest that DPPC has little impact on dissolution behaviour, with polysorbate 80 proving much more effective. DPPC forms liposomal aggregates in aqueous media that have a larger particle size distribution than the membrane pore size.14 It is therefore likely that the DPPC has little effect because it cannot penetrate through the membrane to the sample.

Using polysorbate 80 at an appropriate concentration (0.2%), on the other hand, brings the dissolution profile obtained with a sample loading equating to five actuations close to that obtained with no surfactant, and just a single firing of the device. A single actuation produces a very thin drug layer with negligible resistance to wetting and dissolution. These results suggest that the use of tPBS eliminates the issue of wetting for this particular hydrophobic active.


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