Improved aerosolization performance of salbutamol sulfate formulated with lactose crystallized from binary mixtures of ethanol-acetone.
It has been shown that dry powder inhaler (DPI) formulations typically achieve low fine particle fractions (poor performance). A commonly held theory is that this is due, at least in part, to low levels of detachment of drug from lactose during aerosolization as a result of strong adhesion of drug particles to the carrier surfaces. Therefore, the purpose of the present study is to overcome poor aerosolization performance of DPI formulation by modification of lactose particles. Lactose particles were crystallized by adding solution in water to different ratios of binary mixtures of ethanol-acetone. The results showed that modified lactose particles had exceptional aerosolization performance that makes them superior to commercial lactose particles. Morphology assessment showed that crystallized lactose particles were less elongated, more irregular in shape, and composed of smaller primary lactose particles compared with commercial lactose. Solid-state characterization showed that commercial lactose particles were α-lactose monohydrate, whereas crystallized lactose particles were a mixture of α-lactose monohydrate and β-lactose according to the ratio of ethanol-acetone used during crystallization process. The enhanced performance could be mainly due to rougher surface and/or higher amounts of fines compared with the lactose crystallized from pure ethanol or commercial lactose.
Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, Chatham, Kent ME4 4TB, United Kingdom.
Waseem
W
Kaialy
Martyn D
MD
Ticehurst
John
J
Murphy
Ali
A
Nokhodchi
D000096:Acetone / Q000737:chemistry*; D000268:Adhesiveness; D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000737:chemistry*; D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004337:Drug Carriers; D004339:Drug Compounding; D058995:Dry Powder Inhalers; D000431:Ethanol / Q000737:chemistry*; D007785:Lactose / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D012212:Rheology; D012997:Solvents / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods
D058666:Adrenergic beta-2 Receptor Agonists; D000336:Aerosols; D001993:Bronchodilator Agents; D004337:Drug Carriers; D011208:Powders; D012997:Solvents; D000096:Acetone; D000431:Ethanol; D007785:Lactose; D000420:Albuterol