TY - JOUR
T1 - Novel spherical lactose produced by solid state crystallisation as a carrier for aerosolised salbutamol sulphate, beclomethasone dipropionate and fluticasone propionate
AU - Abadelah, Mohamad
AU - Thevarajah, Ursula
AU - Ahmed, Mahmud
AU - Seton, Linda
AU - Supuk, Enes
AU - Conway, Barbara R.
AU - Larhrib, Hassan
N1 - Publisher Copyright:
© 2021 Elsevier B.V.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - The purpose of the present work was to engineer lactose carrier particles for inhalation using a solid-state crystallisation of amorphous spray dried lactose approach. A suspension of spray dried lactose was contacted with hot ethanol for 10 and 30 s to produce spherical particles (ESDL10) and (ESDL30) with different degrees of crystallinity, particle size, and controlled surface rugosity. Lactohale® (control) and engineered spray dried lactose (ESDL) particles were characterised by Scanning Electron Microscopy, X-ray Powder Diffraction and Tribo-electrification. Lactohale® and engineered lactose particles were mixed separately with salbutamol sulphate (SS), beclomethasone dipropionate (BDP) and fluticasone propionate (FP) and each formulation was assessed for drug content uniformity, drug segregation after tribo-electrification and drug deposition using Andersen Cascade Impactor (ACI). Lactohale® showed the highest but opposite affinity for electrical surface charges compared to engineered lactose. Lactohale® showed the greatest variation in drug content uniformity with SS but to a lesser extent with BDP and FP, whereas the ESDL carriers produced an acceptable uniform mix with all drugs. SS-Lactohale® formulation showed the highest segregation after tribo-electrification up to 119-fold in comparison to that observed with SS-engineered lactose. ESDL10 carrier promoted a better drug deposition for both BDP and FP and showed the least variation in both content uniformity and FPD with all three drugs. Therefore, production of crystalline spherical lactose carrier with controlled surface texture, size and crystallinity is achievable using solid state crystallisation for DPIs, whilst providing less variation in drug content uniformity and consistent fine particle dose to the lungs in-vitro for both hydrophilic and hydrophobic drugs.
AB - The purpose of the present work was to engineer lactose carrier particles for inhalation using a solid-state crystallisation of amorphous spray dried lactose approach. A suspension of spray dried lactose was contacted with hot ethanol for 10 and 30 s to produce spherical particles (ESDL10) and (ESDL30) with different degrees of crystallinity, particle size, and controlled surface rugosity. Lactohale® (control) and engineered spray dried lactose (ESDL) particles were characterised by Scanning Electron Microscopy, X-ray Powder Diffraction and Tribo-electrification. Lactohale® and engineered lactose particles were mixed separately with salbutamol sulphate (SS), beclomethasone dipropionate (BDP) and fluticasone propionate (FP) and each formulation was assessed for drug content uniformity, drug segregation after tribo-electrification and drug deposition using Andersen Cascade Impactor (ACI). Lactohale® showed the highest but opposite affinity for electrical surface charges compared to engineered lactose. Lactohale® showed the greatest variation in drug content uniformity with SS but to a lesser extent with BDP and FP, whereas the ESDL carriers produced an acceptable uniform mix with all drugs. SS-Lactohale® formulation showed the highest segregation after tribo-electrification up to 119-fold in comparison to that observed with SS-engineered lactose. ESDL10 carrier promoted a better drug deposition for both BDP and FP and showed the least variation in both content uniformity and FPD with all three drugs. Therefore, production of crystalline spherical lactose carrier with controlled surface texture, size and crystallinity is achievable using solid state crystallisation for DPIs, whilst providing less variation in drug content uniformity and consistent fine particle dose to the lungs in-vitro for both hydrophilic and hydrophobic drugs.
KW - Beclomethasone dipropionate
KW - Fluticasone propionate
KW - Salbutamol sulphate
KW - Solid state crystallisation
KW - Tribo-electrification
UR - http://www.scopus.com/inward/record.url?scp=85121878389&partnerID=8YFLogxK
U2 - 10.1016/j.jddst.2021.103040
DO - 10.1016/j.jddst.2021.103040
M3 - Article
AN - SCOPUS:85121878389
VL - 68
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
SN - 1773-2247
M1 - 103040
ER -