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

Steven Woolford; Mandy Tran; Coumbe Yoda; Berk Oktem; Agnes NguyenPho; Martin McDermott; Samanthi Wickramasekara

doi:10.1016/j.ijpharm.2022.121749

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

Int J Pharm. 2022 May 25:620:121749. doi: 10.1016/j.ijpharm.2022.121749. Epub 2022 Apr 12.

Authors

Steven Woolford¹, Mandy Tran², Coumbe Yoda¹, Berk Oktem¹, Agnes NguyenPho³, Martin McDermott¹, Samanthi Wickramasekara⁴

Affiliations

¹ Division of Biology, Chemistry, and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD 20993, United States.
² Division of Biology, Chemistry, and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD 20993, United States; Division of Quality Surveillance Assessment, Office of Surveillance, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, United States.
³ Division of Quality Surveillance Assessment, Office of Surveillance, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, United States.
⁴ Division of Biology, Chemistry, and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, MD 20993, United States. Electronic address: Samanthi.Wickramasekara@fda.hhs.gov.

PMID: 35427748
DOI: 10.1016/j.ijpharm.2022.121749

Abstract

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.

Keywords: Drug coated balloons; Excipient; Iopromide; Paclitaxel; Track and Deploy.

Published by Elsevier B.V.

MeSH terms

Antineoplastic Agents* / therapeutic use
Coated Materials, Biocompatible / chemistry
Drug Liberation
Excipients / chemistry
Humans
Paclitaxel / chemistry
Peripheral Arterial Disease* / drug therapy
Treatment Outcome

Substances

Antineoplastic Agents
Coated Materials, Biocompatible
Excipients
Paclitaxel