Investigation of the physical properties of spray-dried stabilised lysozyme particles.
The aim of this study was to investigate the effect of the composition of formulations on the physical properties, including glass-transition temperatures (Tg) and aerodynamic-related characteristics, of spray-dried lysozyme particles. The Tg, as determined by differential scanning calorimetry, of spray-dried lysozyme formulations was found to be dependent upon the type and amount of excipient(s) included in the formulation. In addition, the Tg of sucrose-containing particles appeared to be raised markedly by the inclusion of trehalose, but not by dextran. The surfaces of all spray-dried particles were shown by scanning electron microscopy to be smooth with some containing characteristic dimples, typical of spray-dried material, and the morphology appeared to be independent of variation in excipient composition. However, the volume median diameters (VMD) of spray-dried powders, as determined by laser diffraction, were found to depend upon the amounts of excipients. The fine particle fraction of enzyme delivered to the lower stage of a twin-stage impinger from lysozyme-trehalose 1:1 powders appeared to be greater than that from lysozyme-sucrose 1:1 particles (22.5% vs 15.9%) when dispersed via a Rotahaler although a similar dispersibility of the two formulations (39.6% vs 36.7%) was found from a glass inhaler. In general, spray-drying was demonstrated to be feasible to produce respirable particles of the stabilised model protein, with Tg of the formulations being > 30 degrees C higher than room temperature.
Liao
Yong-Hong
YH
MedPharm, Department of Pharmacy, King's College London, Franklin-Wilkins Building, London, UK.
Brown
Marc B
MB
Quader
Abdul
A
Martin
Gary P
GP
D003460:Crystallization; D003890:Desiccation / Q000379:methods; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D009113:Muramidase / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders; D013395:Sucrose / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D044366:Transition Temperature; D014199:Trehalose / Q000737:chemistry
D005079:Excipients; D011208:Powders; D013395:Sucrose; D014199:Trehalose; D009113:Muramidase