Studying the effect of drug-to-excipient ratio on drug release profile for drug coated balloons.

Drug-coated balloons (DCB) have emerged as the alternative procedure for restenosis because of their ability to treat a variety of occlusion types with a uniform dose of anti-proliferative drugs. DCB are balloons coated with antiproliferative drugs encapsulated in a polymer matrix. There are several types of coating matrices used to produce DCB. In this study, the relationship between coating composition and drug release under physiologically relevant conditions was examined to understand how differences in coating composition impacts the drug transfer from the balloon surface to the simulated body fluids. To conduct the experiments, the balloons were coated with different paclitaxel (drug)-to-iopromide (excipient) ratios (3:1, 3:2 and 1:2) using an in-house developed micro-pipetting method. Scanning electron microscopy (SEM) images showed that the 3:1 PTX:IOP ratio produced a more uniform, crystalline microstructure with a thinner coating throughout the balloon surface compared to the other drug-to-excipient ratios. The 1:2 PTX:IOP ratio showed the least crystalline microstructure among the three ratios evaluated in this study. Three different drug elution conditions were tested. The amount of drug released to the medium was quantified by high performance liquid chromatography (HPLC). Our soaking study and submerge & deploy study showed that ∼20% of the drug transferred to the target site under physiological conditions. A track and deploy method was performed using a "mock" artery, to simulate an in vitro environment. Coated balloons were passed through the mock artery to mimic tracking turns the balloon within the arteries during the angioplasty procedures. Seven elution samples were collected at different stages of the procedure. Drug release results suggest that the higher excipient ratio helps to deliver the lipophilic drug to the target site under simulated conditions but causes higher drug loss during the balloon transfer process.

Optimization of balloon coating process for paclitaxel coated balloons via micro-pipetting method.

Drug coated balloons (DCBs) have proven to be a suitable alternative for the treatment of cardiovascular diseases. They allow for uniform delivery of an antiproliferative drug to the stenotic site without permanent implantation of the device in the patient's body. There are, however, regulatory concerns regarding the lack of data associated with variable drug delivery to the target site, which can be related to the coating process. This study describes the process for an in-house micro-pipetting coating method that incorporates a laboratory-developed coating equation for determining optimal coating parameters. The coating solutions included a common drug of choice, paclitaxel, along with a hydrophilic excipient, such as iopromide. It was found that using a revolution rate of 240 rev/min, a flow rate of 25 µL/min and a translational speed of 0.033 cm/s resulted in visually uniform coatings. High performance liquid chromatography (HPLC) allowed for the determination of paclitaxel content on the balloon surface. Scanning electron microscopy (SEM) enabled analysis of coating thickness and texture at distal, middle, and proximal positions on the balloon; average thicknesses were determined to be 16.4 ±â€¯5.8, 14.8 ±â€¯1.4, and 18.1 ±â€¯3.9 µm, respectively. These optimized coating conditions have been confirmed by in vitro drug release kinetics studies. Overall this study generated a simple and reproducible micro-pipetting coating method for the sustained release of drugs from the drug coated balloons.

Evaluation of three influenza neuraminidase inhibition assays for use in a public health laboratory setting during the 2011-2012 influenza season.

OBJECTIVES: We evaluated the implementation of three commercially available neuraminidase inhibition assays in a public health laboratory (PHL) setting. We also described the drug susceptibility patterns of human influenza A and B circulating in Maryland during the 2011-2012 influenza season. METHODS: From January to May 2012, 169 influenza virus isolates were tested for phenotypic susceptibility to oseltamivir, zanamivir, and peramivir using NA-Fluor(TM), NA-Star®, and NA-XTD(TM) concurrently. A 50% neuraminidase inhibitory concentration (IC50) value was calculated to determine drug susceptibility. We used the standard deviation based on the median absolute deviation of the median analysis to determine the potential for reduced drug susceptibility. We evaluated each assay for the use of resources in high- and low-volume testing scenarios. RESULTS: One of the 25 2009 influenza A (H1N1) pandemic isolates tested was resistant to oseltamivir and peramivir, and sensitive to zanamivir, on all three platforms. Eighty-two influenza A (H3N2) and 62 B isolates were sensitive to all three drugs in all three assays. For a low-volume scenario, NA-Star and NA-XTD took 120 minutes to complete, while NA-Fluor required 300 minutes to complete. The lowest relative cost favored NA-Star. In a high-volume scenario, NA-Fluor had the highest throughput. Reagent use was most efficient when maximizing throughput. Cost efficiency from low- to high-volume testing improved the most for NA-Star. CONCLUSIONS: Our evaluation showed that both chemiluminescent and fluorescent neuraminidase inhibition assays can be successfully implemented in a PHL setting to screen circulating influenza strains for neuraminidase inhibitor resistance. For improved PHL influenza surveillance, it may be essential to develop guidelines for phenotypic drug-resistance testing that take into consideration a PHL's workload and available resources.