Process optimization of spray-dried fanhuncaoin powder for pulmonary drug delivery and its pharmacokinetic evaluation in rats

Abstract

The optimization of process parameters of spray-dried powder containing fanhuncaoin, a newly discovered anti-inflammatorily active phenolic acid isolated from Chinese herb, was conducted using response surface methodology (RSM). The experimental results were fitted into partial cubic polynomial model to describe and predict the response quality in terms of the final angle of repose, aerodynamic diameter, respirable fraction (RF), and yield. The recommended optimum spray-drying parameters for the development of fanhuncaoin powder with optimum quality were 110 °C inlet temperature, 0.50 m³/min aspiration speed, and 7.95 ml/min feed flow rate. The obtained optimum process parameters were employed for the production of spray-dried fanhuncaoin powder and to check the validity of the partial cubic model. Small and insignificant deviations were found between the predicted values and the experimental ones, showing the efficiency of the model in predicting the quality attributes of fanhuncaoin powder. The optimized powder was further examined for its pharmacokinetic properties in rats. A UPLC/MS assay was used to determine plasma fanhuncaoin concentration. Statistical analysis demonstrated that there was no significant difference in the t_1/2 and dose-normalized C_max and AUC as well as other pharmacokinetic parameters between the groups dosed differently following intratracheal administration (p > .05), indicating that fanhuncaoin followed linear kinetics. The pharmacokinetic parameters of fanhuncaoin after intratracheal administration differed significantly from the ones observed after intravenous administration (p < .05). The lower values of C_max and AUC_(0-∞) obtained following intratracheal administration may lead to effective drug concentrations at the target site with minimal systemic bioavailability and side effects.

Keywords:

• Response surface methodology
• optimization
• spray-drying
• fanhuncaoin
• inhalation

Disclosure statement

The authors confirm that this article content has no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant no. [81502992] and the Ministry of Science and Technology under Grant no. [2009ZXJ09002-019]. The authors would like to acknowledge Prof. Guozhu Han for the language check.