Cyclodextrin as a potential drug carrier in salbutamol dry powder aerosols: the in-vitro deposition and toxicity studies of the complexes.
This research was carried out to develop a new carrier in dry powder aerosols. Two types of cyclodextrin were chosen; gamma cyclodextrin (GCD) and dimethyl-beta-cyclodextrin (DMCD) as carriers in dry powder formulations. Salbutamol was used as a model drug and a control formulation containing lactose and the drug was included. A twin-stage impinger (TSI) was used to evaluate in delivery efficiency of those dry powder formulations. The toxicity of cyclodextrin complexes was investigated in the rat by monitoring blood urea nitrogen (BUN) and urinary creatinine, as well as determining haemolysis of human red blood cells. The release of salbutamol from dry powder formulations was also studied over a period of time. From the results obtained, it was found that the formulation containing GCD-enhanced drug delivery to the lower stage of the TSI (deposition = 65%) much greater than that of both formulations containing DMCD (50%) and the control formulation (40%) (P<0.05). After injecting the GCD complex BUN and creatinine levels in rats were similar to those obtained in the control while those receiving DMCD complex had higher BUN and creatinine. The haemolysis of red blood cells incubated with the DMCD complex was higher than that obtained in the GCD complex. The drug release in both formulations containing GCD and DMCD was fast (over 70% was released in 5 min) and nearly all the drug was released within 30 min. It can be concluded that GCD and DMCD are able to promote salbutamol delivery in dry powder inhaler compared to a formulation containing lactose. In addition, GCD is relatively safe in the rat if the amount of GCD in the formulation is similar to this experiment.
Srichana
T
T
Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkhla University, Hat-Yai, Thailand.
Suedee
R
R
Reanmongkol
W
W
D000336:Aerosols; D000420:Albuterol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000704:Analysis of Variance; D000818:Animals; D001806:Blood Urea Nitrogen; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000652:urine; D003505:Cyclodextrins / Q000494:pharmacology*; D004337:Drug Carriers; D004353:Drug Evaluation, Preclinical; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D000336:Aerosols; D003505:Cyclodextrins; D004337:Drug Carriers; D003404:Creatinine; D000420:Albuterol