Preformed cyclodextrin-salbutamol complexes as a potential ingredient in dry powder inhalers

Preformed cyclodextrin-salbutamol complexes as a potential ingredient in dry powder inhalers

Teerapol Srichana, D. of Pharmaceutical Tech., F. of Pharmaceutical Sci., PSU.
Roongnapa Suedee, Asst. Prof., D. of Pharmaceutical Chemistry, F. of Pharmaceutical Sci., PSU
. Wantana Reanmongkol, Assoc. Prof., D. of Clinical Pharmacy, F. of Pharmaceutical Sci., PSU.
Corresponding e-mail : srteerap@ratree.psu.ac.th

Grant : Prince of Songkla University
Published : Research Report
Key words : cyclodextrin-salbutamol complexes, dry powder inhalers

At present dry powder formulation employed lactose as a carrier. Although the efficiency of drug delivery to the targeted organ was quite low at about 10% of the nominal dose. This research report seeks to develop a new carrier which enhance the drug delivery and release fast while it is safe. In this study two types of cyclodextrin were chosen; gamma cyclodextrin (GCD) and dimethyl-eta-cyclodextrin (DMCD), as a carrier in the preformed salbutamol-CD complex. The complex was freeze-dried before being characterised by FTIR, DSC and XRD. The freeze dried complexes were then micronised before use as an ingredient in dry powder inhaler. Lactose was used as a diluent. Twin Stage Impiner (TSI) was employed to evaluate dry powder formulation as divided delivery dose into two fractions; upper and lower stages deposition which were used to represent upper and lower airways, respectively. These studies were carried out to quantify both salbutamol and cyclodextrins deposition. The cyclodextrins found in the lower stage was used to investigate the toxicity in rat by monitoring blood urea nitrogen and creatinine over a period of one month after intraperitoneal injec-tion of cyclodextrins. The hemolysis was conducted by incubated various concentrations of cyclo-dextrins with human red blood cells. Also the release of salbutamol from dry powder formulations were studied over a period of time. The result revealed that salbutamol can form a complex with GCD and DMCD. DMCD increased solubility of salbutamol much better than that of GCD as confirmed by phase solubility profile. The interaction between salbutamol and cyclodextrin was confirmed by FTIR, DSC, XRD. When dry powder formulation containing cyclodextrins was tested delivery efficiency; it was found that GCD enhanced drug delivery in the formulation and the control for- mulation. GCD in safer than DMCD as the BUN and creatinine level found in rat after having been injected cyclodextrins were similar to those obtained in the control. The hemolysis of red blood cell incubated in DMCD was higher than that obtained in GCD. The drug release in both GCD and DMCD containing formulations was fast, over 70% was released in 5 min and nearly all drug was released within 30 min. These can be concluded that GCD is able to promote salbutamol delivery in dry powder inhaler and it is safe in rat whilst it releases fast. Therefore it is reasonable to be consider as an alternative carrier to lactose.

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