The influence of physical properties and morphology of crystallised lactose on delivery of salbutamol sulphate from dry powder inhalers

Abstract

The aim of this work was to investigate the mechanistic evaluation of physicochemical properties of new engineered lactose on aerosolisation performance of salbutamol sulphate (SS) delivered from dry powder inhaler (DPI). Different crystallised lactose particles were obtained from binary mixtures of butanol:acetone. The sieved fractions (63-90 μm) of crystallised lactose were characterised in terms of size, shape, flowability, true density and aerosolisation performance (using multiple twin stage impinger (MSLI), Aerolizer(®) inhaler device, and salbutamol sulphate as a model drug). Compared to commercial lactose, crystallised lactose particles were less elongated, covered with fine lactose particles, and had a rougher surface morphology. The crystallised lactose powders had a considerably lower bulk and tap density and poorer flow when compared to commercial lactose. Engineered carrier with better flow showed improved drug content homogeneity, reduced amounts of drug "deposited" on the inhaler device and throat, and a smaller drug aerodynamic diameter upon inhalation. Aerodynamic diameter of salbutamol sulphate increased as lactose aerodynamic diameter decreased (linear, R(2)=0.9191) and/or as fine particle lactose content increased (linear, R(2)=0.8653). Improved drug aerosolisation performance in the case of crystallised lactose particles was attributed to lower drug-carrier adhesion forces due to a rougher surface and higher fine particle content. In conclusion, this work proved that using binary combinations of solvents in crystallisation medium is vital in modification of the physicochemical and micromeritic properties of carriers to achieve a desirable aerosolisation performance from DPI formulations. Among all lactose samples, lactose particles crystallised from pure butanol generated the highest overall DPI formulations desirability.

The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices—The use of the USP III apparatus

“…Optical image analysis microscopy was employed to quantify shape of the HPMC E4M and K4M particles using several shape descriptors including roundness [21] and roughness [22].…”

Influence of Batch Cooling Crystallization on Mannitol Physical Properties and Drug Dispersion from Dry Powder Inhalers

“…For example, it has been shown that higher amounts of drug could be delivered to lower airway regions by decreasing the mean size of either drug particles 8 or carrier particles. 9,10 The presence of fine particles on the carrier surface has improved the inhalation performance of DPI formulations by decreasing the drug-carrier contact area and consequently reducing drugcarrier adhesion forces. 7,11 Surface morphology of carrier particles has been modified in order to obtain improved drug dispersion properties, where smoother surface 6,12 or higher specific surface area 12,13 produced a higher fine particle fraction of drug.…”

Preparation and In Vitro Aerosol Performance of Spray-Dried Shuang-Huang-Lian Corrugated Particles in Carrier-Based Dry Powder Inhalers

“…Liberation of particles from the carrier surfaces is dictated by the magnitude of drug-carrier adhesive forces, and excessive adhesive forces could prevent detachment of drug from the carrier surfaces, leading to poor detachment (18,(31)(32)(33)(34)(35)(36), therefore an increase in the surface roughness of SHL particles could be assumed to result in the reduction in the particle-carrier adhesive forces and subsequently leading to the improved detachment efficiency. In fact, such an assumption was supported by the findings from a previous study (15).…”