Characterisation and deposition studies of engineered lactose crystals with potential for use as a carrier for aerosolised salbutamol sulfate from dry powder inhalers.
Lactose particles with different elongation ratio, roundness, polymorphic form and crystallinity were prepared by a one-step crystallisation process using varying ratios of acetone/water. The crystals were characterised using image analysis optical microscopy, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffraction. The elongation ratio was found to increase with increasing acetone ratio which therefore, appears to accelerate the growth in length rather than width and/or thickness. The crystallinity and polymorphic forms were also acetone-concentration dependent. For example, the crystals formed using 65-80% v/v acetone were almost all of the alpha-form whereas at 85% v/v a small amount of beta-form was precipitated, as detected by a peak at the reflection angle 2 theta=10.4 in the X-ray diffractogram. When 90% v/v acetone was incorporated a mixture of alpha- and beta-forms were produced in almost equal quantity, whereas, with 95% v/v acetone the beta-form predominated. At high acetone concentration (90 and 95% v/v), the crystallisation proceeded rapidly leading to the creation of some amorphous content. The 63-90-microm sieve cut of either commercial grade lactose (CL) or crystallised lactose was mixed with salbutamol sulfate and dispersibility was determined using the twin stage liquid impinger. All the formulations containing carrier particles generated by crystallization from solvent showed higher dispersibility and fine particle fraction (FPF) of the drug compared to the formulation made containing CL. The carrier that showed the highest elongation ratio (produced from an 85% acetone 15% water solution), when mixed with salbutamol sulfate produced the highest dispersibility (38.5%) and highest FPF (29.24%). These parameters were six times higher than the values obtained with the formulation containing CL.
Larhrib
Hassan
H
Department of Pharmacy, King's College London, 150 Franklin-Wilkins Building, Stamford Street, London SE1 9NN, UK.
Martin
Gary P
GP
Prime
David
D
Marriott
Christopher
C
D000096:Acetone; D000280:Administration, Inhalation; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D004337:Drug Carriers; D007785:Lactose / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D011208:Powders; D014961:X-Ray Diffraction
D000336:Aerosols; D004337:Drug Carriers; D011208:Powders; D000096:Acetone; D007785:Lactose; D000420:Albuterol