Carrier Based Systems

The majority of DPI products use the carrier-based formulation system. This approach has proved successful for a range of dosing regimes from high dose, that is, up to several hundred micron, for example, 400 ^g for albuterol sulphate to low dose, for example, <12 ^g for formoterol. In the 1970s, Hersey theorized that when small particles were mixed with larger particles (such as conventional carrier material) a so-called ordered mix was formed (16). Although these observations were deemed relevant to low dose tablet formulations, this theory was later expanded in the 1980s and 1990s by Staniforth (17), and has since become an underlying theory for carrier based DPI powder formulations. In general, this approach has been

Drug Designing Conventional Way
Figure 3 Conventional DPI formulation approaches

adopted by the pharmaceutical industry to produce many successful inhalation products, and, interestingly, as a way of preparing low dose blends for tableting applications. These simple DPI formulations are typically prepared by mixing micronized drug with larger lactose carrier particles. The drug adheres to the larger particles in such a way that results in good blend uniformity and flow. Additionally, and importantly, when the formulation is delivered to the patient via a device, the drug particles are liberated to provide a reliable efficacious dose to the patient. This technique has been proven to be versatile and has been used to develop products which contain low dose drugs products, for example, NovartisĀ® 12 ^g formoterol ForadilĀ® product, equivalent to a c.a. 0.05%w/w drug/ carrier blend. To put this achievement in powder blend and emitted dose uniformity into perspective, an image of a low dose Foradil blend is shown in Figure 4. As can be seen from Figure 4, the formulation consists of a mixture of larger carrier particles together with associated lactose fines and drug particulates. The relative surface distribution of drug particles to carrier material will be very low and yet the product provides good dose uniformity. The same is true for higher dose formulations which contain several hundred micrograms of drug which contain higher ratios of drug to carrier. However, the important point with drug loading in DPIs is that the drug will be associated with the surface of the carrier, making the surface ratios much higher than mass ratios. Obviously, for all DPI products, carriers and drugs with consistent physiochemical characteristics are required to maintain product performance. This dependency on material characteristics has implications for drug aerosolization (liberation) performance if variations in API adhesion exist throughout the carrier system.

Continue reading here: Agglomerated Systems

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