The use of different grades of lactose as a carrier for aerosolised salbutamol sulphate

Five different grades of lactose namely, anhydrous lactose, medium lactose, regular lactose, lactose crystals and foremost lactose were fractionated u nder similar conditions to obtain a size range of 63-90 mu m and were chara cterised using laser diffraction and time-of-flight particle sizing techniq ues, scanning electron microscopy, optical microscopy image analysis, therm al gravimetric analysis and differential scanning calorimetry. Each of thes e lactose fractions were then blended separately with micronised salbutamol sulphate in a ratio of 67.5:1 (w/w). The mixing uniformity and percentage recovery of salbutamol sulphate in the powder blends were analysed using a validated HPLC method. The deposition profiles of the drug were determined using a 5-stage liquid impinger after aerosolisation at 60 l min(-1) via a Rotahaler. Despite the identical processing conditions, the lactose fractio ns were shown to differ in particle size, size distribution and concentrati ons of fine particles. The particles from each fraction also exhibited diff erent surface textures and dissimilar DSC thermograms. However, all the ble nds of the lactose with salbutamol sulphate were found to have a relatively high uniformity of salbutamol sulphate content, as suggested by a coeffici ent of variation of less than 3.2%. Anhydrous and medium lactose produced a more efficient delivery of salbutamol sulphate when aerosolised from the R otahaler in comparison to other grades of lactose. For example, the fine pa rticle fraction (FPF) and fine particle dose (FPD) of drug fi-om formulatio ns containing anhydrous lactose were 13.4 +/- 4.2% and 57.3 +/- 17.6 mu g, respectively, which were approximately two times higher than the respective values of the formulation containing regular lactose. Medium lactose resul ted in drug FPF (7.9 +/- 2.7%) and FPD (32.4 +/- 11.8 mu g), which were sig nificantly (ANOVA P < 0.05) higher than the same parameters obtained using lactose crystals, foremost lactose and regular lactose. More efficient drug delivery from anhydrous lactose may be partly attributed to the relatively higher concentration of fine lactose in this grade of carrier, although it showed a rougher surface than the other grades of lactose. However, the re latively high FPF of the drug from medium lactose may have been due to the relatively small mean particle size and smooth surface of the particles. Th erefore, the source and grade of lactose may have a substantial effect on d rug delivery from dry powder inhaler formulations and care should be taken in establishing appropriate quality control parameters when selecting an ap propriate grade of carrier. (C) 1999 Elsevier Science B.V. All rights reser ved.