(005) Can Novel SDS-089 Nasal Vardenafil Spray Solution Achieve Satisfactory Drug Plasma Level Similar to Oral Vardenafil Formulation? A Bioanalysis Study Comparing Vardenafil Nasal vs Oral Formulations Using Liquid Chromatography Tandem Mass Spectrometry

Abstract

Abstract Introduction The nasal drug delivery system offers many advantages when compared with oral administration, such as a faster onset of action, easily accessible, less drug degradation, and a high rate of absorption. The SDS-089 nasal Vardenafil (VDF) solution is a unique drug formulation designed to be delivered as a spray formulation. Objective To assess the bioavailability of SDS-089 nasal Vardenafil solution in human plasma levels using Liquid Chromatography Tandem Mass Spectrometry analysis. Methods The SDS-089 Vardenafil HCl formulation was prepared with the active pharmaceutical ingredient to the United States Pharmacopeia (USP) standard (batch 1704002361). The SDS-089 nasal spray solution was filtered (0.22 μm filter) and fitted with a nasal spray device to deliver 100 μL per spray which is equivalent to 2 mg Vardenafil HCl alcoholic solution per spray. This study received approval from the Institutional Review Board and Biosafety Committee (FB18/IRB/099). Blood samples from participants were collected at time 0 (pre-dose) and across different time intervals up to 10 hours and analyzed using Liquid Chromatography Tandem Mass Spectrometry (LC/MS) to quantify the level of Vardenafil and the internal standard. This protocol allows for the preparation and analysis of human samples, quality controls (QC), standard curve preparation, and instrumental analysis. During the validation experiments, each calibration standard and QC sample was prepared by spiking a specified amount of Vardenafil in human plasma with oral Vardenafil drug served as the internal standard for comparison. The concentration of analytes in each standard was quantified using LC/MS and detected using multiple-reaction monitoring for each of the respective analytes. The lower limit of quantitation (LLOQ) was defined as the lowest concentration that could be quantified with accuracy and precision within 20%, as calculated from chromatograms for the independent samples. Intra- and inter-run accuracy and precision were calculated for the three QC samples, and independent triplicate measurements with best-fit lines were selected using a linear regression model with a 1/x2 weighting factor in the calibration curves. Results The SDS-089 nasal Vardenafil solution showed excellent accuracy (mean 100, Standard Deviation, SD 4.1, % Relative Standard Deviation, RSD of 4%) and good precision (mean 50.1, SD 2.1, %RSD of 4%) on high (50ng/ml) QC assay tests. Similarly, the stability of QC on high (50ng/ml) plasma assay tests showed excellent accuracy (mean 100.8, SD 3.7, %RSD of 4%) and good precision (mean 50.4, SD 1.8, %RSD of 4%) on high (50ng/ml). Comparison between pharmacokinetic parameters of Vardenafil SDS-089 nasal spray (4mg) and oral tablet (10mg) showed T1/2 (2.52±0.99 vs 2.46±0.73 hour), Tmax (0.17±0.54 vs 0.97±0.35 hour), Cmax (time concentrations) (9.21±4.11 vs 11.24±7.83 ng/mL) and AUC0-inf (area under the curve from zero to infinity) (21.03±12.54 vs 37.25±41.51 ng/mL*h) (see Table 1: Pharmacokinetic parameters of Vardenafil HCI as SDS-089 nasal spray vs. oral tablet using non-compartmental analysis WinNonlin software). Conclusions SDS-089 nasal formulation appeared to deliver a high plasma concentration level of Vardenafil drug based on pharmacokinetic LC/MS data analysis with robust accuracy and precision. Disclosure Yes, this is sponsored by industry/sponsor: LTR Pharma Clarification: Industry funding only - investigator initiated and executed study