Pharmacokinetics of Afatinib after Intravenous and Oral Administrations in Rats Using Validated UPLC MS/MS Assay.

Afatinib is designated as the first-line management therapy for patients with advanced non-small cell lung cancer, and metastatic head and neck cancer. LC coupled to MS/MS can be utilised in therapeutic drug monitoring to ensure optimal use of Afatinib with the reduction of its possible adverse reactions. The aim of this investigation was to determine the pharmacokinetics of Afatinib in rats after single IV (2 mg/kg) and oral (8 mg/kg) doses. Therefore, a selective, sensitive and precise UPLC MS/MS assay thru electrospray ionisation basis with positive ionisation approach was established to measure Afatinib concentrations in the rat. The precision and accuracy of the developed assay method in the concentration range of 10-1000 ng/ml show no significant difference among inter- and-intra-day analysis (P > 0.05). Linearity was detected over the studied range with correlation coefficient, r > 0.995 (n = 6/day). The pharmacokinetics of Afatinib in the rat after a single IV dose showed a mean terminal half-life of 4.6 ± 0.97 h, and a mean clearance 480 ± 80 ml/h/kg. After PO administration, a short absorption phase with a mean Tmax of 1.3 ± 0.6 h with the highest concentration of 513.9 ± 281.1 ng/ml, and the lowest concentration detected after 24 h was 18.8 ± 10.7 ng/ml.

Development of Inhalable Nanostructured Lipid Carriers for Ciprofloxacin for Noncystic Fibrosis Bronchiectasis Treatment.

PURPOSE: Ciprofloxacin (CIP) has poor lung targeting after oral inhalation. This study developed optimized inhalable nanostructured lipid carriers (NLCs) for CIP to enhance deposition and accumulation in deeper parts of the lungs for treatment of noncystic fibrosis bronchiectasis (NCFB). METHODS: NLC formulations based on stearic acid and oleic acid were successfully prepared by hot homogenization and in vitro-characterized. CIP-NLCs were formulated into nanocomposite micro particles (NCMPs) for administration in dry powder inhalation (DPI) formulations by spray-drying (SD) using different ratios of chitosan (CH) as a carrier. DPI formulations were evaluated for drug content and in vitro deposition, and their mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), fine particle dose (FPD), and emitted dose (ED) were determined. RESULTS: The CIP-NLCs were in the nanometric size range (102.3 ± 4.6 nm), had a low polydispersity index (0.267 ± 0.12), and efficient CIP encapsulation (98.75% ± 0.048%), in addition to a spherical and smooth shape with superior antibacterial activity. The in vitro drug release profile of CIP from CIP-NLCs showed 80% release in 10 h. SD of CIP-NLCs with different ratios of CH generated NCMPs with good yield (>65%). The NCMPs had a corrugated surface, but with increasing lipid:CH ratios, more spherical, smooth, and homogenous NCMPs were obtained. In addition, there was a significant change in the FPF with increasing lipid:CH ratios (P ˂ 0.05). NCMP-1 (lipid:CH = 1:0.5) had the highest FPD (45.0 µg) and FPF (49.2%), while NCMP-3 (lipid:CH = 1:1.5) had the lowest FPF (37.4%). All NCMP powders had an MMAD in the optimum size range of 3.9-5.1 µm. CONCLUSION: Novel inhalable CIP NCMP powders are a potential new approach to improved target ability and delivery of CIP for NCFB treatment.