Pulmonary delivery of scutellarin solution and mucoadhesive particles in rats

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 70; no. 3; pp. 845 - 852
• Main Authors: Liu, Xiao-Bin, Ye, Jun-Xiao, Quan, Li-Hui, Liu, Chun-Yu, Deng, Xu-Liang, Yang, Ming, Liao, Yong-Hong
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.11.2008; Elsevier
• Subjects: Adhesiveness; Administration, Inhalation; Administration, Oral; Aerosols; Animals; Apigenin - administration & dosage; Apigenin - chemistry; Apigenin - pharmacokinetics; Apigenin - toxicity; Biological and medical sciences; Biological Availability; Bufonidae; Cell Line; Cell Survival - drug effects; Chemistry, Pharmaceutical; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - chemistry; Drugs, Chinese Herbal - pharmacokinetics; Drugs, Chinese Herbal - toxicity; Excipients - chemistry; Excipients - toxicity; Feasibility Studies; Flavonoids; General pharmacology; Glucuronates - administration & dosage; Glucuronates - chemistry; Glucuronates - pharmacokinetics; Glucuronates - toxicity; Humans; Hyaluronan; Hyaluronic Acid - chemistry; Injections, Intravenous; Intratracheal spray; Intravenous delivery; Male; Materials Testing; Medical sciences; Mucociliary Clearance; Mucociliary transport; Particle Size; Permeability; Peroral delivery; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyvinyl Alcohol - chemistry; Povidone - chemistry; Pulmonary delivery; Rats; Rats, Wistar; Respiratory Mucosa - metabolism; Scutellarin; Surface Properties; Scutellarin; Hyaluronan; Flavonoids; Peroral delivery; Intravenous delivery; Pulmonary delivery; Intratracheal spray; Mucociliary transport; Intravenous administration; Rat; Mucosa; Vehicle(excipient); Flavonoid; Particle; Polyphenol; Healing agent; Antirheumatic agent; Bioadhesive system; Solution; Pharmaceutical technology; Controlled release form; Rodentia; Intrapulmonary administration; Bioavailability; Inhalation; Vertebrata; Mammalia; Drug vehicle interaction; Animal; Sodium hyaluronate; Dosage form; Phenols; Hyaluronic acid; Pharmacokinetics; Transport
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2008.07.004

The objectives of this study were to investigate the effects of mucoadhesive excipients on systemic bioavailability of an inhaled drug and to evaluate the feasibility of using the pulmonary route for non-invasive systemic delivery of scutellarin, a poorly orally absorbed flavonoid glucuronide. Following intratracheal spray of the scutellarin solution, the bioavailability was found to be approximately 77% in rats, which was >30-fold higher than that via the peroral route. In addition, the pulmonary absorption of scutellarin appeared to avoid the intestinal first-pass metabolism accompanied by peroral administration. Spray-dried scutellarin particles with the presence of mucoadhesive excipients were found to affect the corresponding mucociliary transport rate (MTR) as evaluated by a frog palate model. The pharmacokinetic results indicated that the magnitude of AUC 0–480 of intrapulmonary delivered drug particles was not correlated to the fine particle fraction (FPF) but inversely related to the MTR. Incorporating mucoadhesive polymeric mixtures into the scutellarin particles, the MTR decreased by sixfold, and the absolute bioavailability of the drug was found to increase from 70.1% to 97.9% despite a decrease in the FPF. Moreover, in vitro results evaluated using Calu-3 and A549 cell lines showed that scutellarin and spray-dried particles with or without the presence of mucoadhesives exhibited no local cell cytotoxic effects in the tested concentration range. In conclusion, the conducting airway is well permeable to scutellarin, and scutellarin may be effectively delivered systemically through inhalation of respirable droplets or particles.