ABSTRACT
Powder formulations comprising inhalation grade lactose and a mimic drug (cholesterol) were prepared using a high shear blending process for which the total energy input could be quantified. The formulations were fluidised in a classic fluidised bed system, to determine whether blending-induced changes could be determined through either bulk fluidisation behaviour or the characteristics of elutriated fractions from the powder beds. The evolution of the fluidisation regime within the powder beds (Δ pressure vs. superficial gas velocity) and total mass of elutriated material were not sensitive measures to differentiate between blended and unblended samples. However, blended and unblended material could be distinguished by the size distributions of the elutriated fractions. The study also showed that there were no further changes in the size distribution of the elutriated fractions once a chemically homogenous mixture of lactose and drug had been produced. However, further blending beyond this 'point of homogeneity' continued to change the lactose particle size distribution of the bulk powder; this may have implications for blend end point determination for these types of formulation.
Subject(s)
Cholesterol/administration & dosage , Excipients/chemistry , Lactose/chemistry , Administration, Inhalation , Chemistry, Pharmaceutical/methods , Cholesterol/chemistry , Dry Powder Inhalers , Particle Size , Powders , Technology, Pharmaceutical/methodsABSTRACT
alpha-Lactose monohydrate is an important pharmaceutical excipient used extensively in dry powder inhaler (DPI) formulations. The ways in which a high shear blending process affect this material have been investigated and important process parameters have been identified. Total energy input (kJ/kg), blade design and the conditions in which lactose was stored prior to blending were found to have the most significant effect on the apparent particle size distribution of the processed material, which may subsequently affect the performance of DPI formulations. The power conditions used during blending, equipment temperature and humidity of the headspace above the powder were found to be less important in this respect. Additionally, it was found that high energy blending could induce changes in the water sorption characteristics of the material, although the formation of amorphous material could not be confirmed.
