Inhalation Products

INHALATION PRODUCTS

Solid particles are employed in two types of inhalation product: the pressurized metered-dose inhaler (pMDI) and the dry powder inhaler (DPI). In both cases, the method of choice for manufacturing particles in an appropriate size range to deposit in the lungs (<5 μm) is attrition milling by air jet mill.

The pMDI product is prepared as a nonaqueous suspension in which surfactant is used to disperse the drug particles in high–vapor pressure pro-pellants. Once the particles are prepared, the product formulation depends only on the particle dispersion in suspension, their ease of redispersion, and their physical stability upon aerosolization. Figure 14.9 shows a typical filling line for pMDI product.

DPI formulations usually involve a combination of the micronized drug with a carrier, notably lactose. The carrier particles are usually larger than the drug particles and outside the range required for lung deposition (>30 mm). The purpose of these large particles is to help disperse the respirable drug particles carrying them into the inspiratory airflow where they are stripped from the surface as a function of the large shear forces. These formulations are prepared in capsules, blisters, or reservoir devices. The filling technology has been developed to accurately meter small doses into the unit-dose packaging.

Other methods of particle preparation have been evaluated, including spray drying and supercritical fluid manufacture. The capacity to manufacture particles with known and optimized particle size, shape, and surface charac-teristics is intriguing, and it seems likely that these methods will become more significant in the future and may even surpass micronization for aerosol delivery of drugs.

FIGURE 14.9 Metered-dose inhaler filling line.