Effects of direct spiking of silicone oil into a model pMDI formulation

Abstract

Context: Silicone oil is used as a valve lubricant in pressurized metered dose inhalers (pMDIs). Its possible impact on drug delivery, through such effects as particle aggregation, has recently been discussed. Objective: To examine the effects of a range of directly spiked silicone oil amounts on pMDI performance. Materials and methods: pMDI canisters containing a corticosteroid medicinal compound, HFA134a and accurately measured amounts of silicone oil (0, 200, 400 and 550 mu g) were prepared. Samples were characterized for actuation weight, aerodynamic size (by Andersen cascade impaction, ACI), charge (by electrical low-pressure impaction, ELPI) and product appearance by visual imaging. Results and discussion: Actuation weights were unaffected by silicone oil. A small increase in aerodynamic size was observed in the presence of silicone oil as a shift from stage 5 to impactor throat. No significant change in medicinal compound recovery was seen (t-tests, p > 0.05). Fine particle fraction as a percentage of dose delivered (FPF) was unchanged, as was particle size distribution derived from charge measurements, with the addition of silicone oil (t-tests, p > 0.05). Canister opening did not indicate container interaction but that sedimentation occurred in the presence of silicone oil. Decanted suspensions containing silicone oil were more transparent. Possible interactions inside and outside the pMDI canister are described. Conclusion: As demonstrated previously with an alternative experimental design the study showed that silicone oil has little effect on product performance, when added to a model pMDI formulation at levels that could potentially be observed as a leachable from the metering valve