The blend was than tableted on a RoTab R&D tableting machine with gravimetric feed producing 9mm round tablets having used flat faced tooling. Blend sampling was performed with a plastic sampling thief from the jar, targeting 5 layers and four positions within the jar (20 samples). The remaining lactose was added and mixed for another 5 minutes, followed by a 2 minutes mixing step with 0.5%w/w Magnesium Stearate and filled into a plastic 2 liter jar.
This mixture was passed through a 500 micron sieve. The API was mixed with 60%w/w of the chosen lactose (SuperTab® 11SD a spray dried round grade of lactose and SuperTab® 21AN an anhydrous shard like lactose) in a Turbula mixer for 8 minutes (90rpm). The API was screened through a 500 micron sieve before use. Methods:Formulations with 0.5 to 0.005% w/w Salbutamol Sulfate (x50 = 18 micron, x90 = 42 micron) were produced on a 1 kilogram scale. In addition, some considerations regarding the API are discussed. This instead of the traditional wet granulation processes using for low dose formulations. The aim of the study is to show that by utilizing the morphology of DC lactoses a highly homogeneous blend and tablet can be achieved with a non-optimized mixing process. To achieve a desired API content uniformity, apart from the functional excipients used and mixing method the API size and size distribution is key (Rohrs, et al., 2006). For poorly flowing and cohesive drug substances this is difficult to achieve.
The small amounts of drug substances have to be distributed evenly (and without segregation) in a powder blend. Due to this trend the formulations for OSD will be in low doses, especially when the therapeutic window is narrow.
Introduction: There are an increasing number of highly potent and selective drugs being discovered (Bi, M et al., 2011). The study shows that utilizing the correct functional excipient – like SuperTab® 11SD – can in combination with the correct API size range and blending steps be an alternative for very low dose formulations. This study shows the advantage of spray dried lactose (Eg:SuperTab® 11SD) in a non-optimized mixing process. In terms of morphology, it is clear that spray dried lactose (Eg:SuperTab® 11SD) has the smoothest surface area to achieve good drug particle de-agglomeration and adherence. Purpose:It is known that Functional DC grades can be used in very low dose API formulations utilizing a simple mixing process.
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