Benefits of polidocanol endovenous microfoam (Varithena®) compared with physician-compounded foams

Abstract

Objective: To compare foam bubble size and bubble size distribution, stability, and degradation rate of commercially available polidocanol endovenous microfoam (Varithena®) and physician-compounded foams using a number of laboratory tests.

Methods: Foam properties of polidocanol endovenous microfoam and physician-compounded foams were measured and compared using a glass-plate method and a Sympatec QICPIC image analysis method to measure bubble size and bubble size distribution, Turbiscan™ LAB for foam half time and drainage and a novel biomimetic vein model to measure foam stability. Physician-compounded foams composed of polidocanol and room air, CO2, or mixtures of oxygen and carbon dioxide (O2:CO2) were generated by different methods.

Results: Polidocanol endovenous microfoam was found to have a narrow bubble size distribution with no large (>500 µm) bubbles. Physician-compounded foams made with the Tessari method had broader bubble size distribution and large bubbles, which have an impact on foam stability. Polidocanol endovenous microfoam had a lower degradation rate than any physician-compounded foams, including foams made using room air (p < 0.035). The same result was obtained at different liquid to gas ratios (1:4 and 1:7) for physician-compounded foams. In all tests performed, CO2 foams were the least stable and different O2:CO2 mixtures had intermediate performance. In the biomimetic vein model, polidocanol endovenous microfoam had the slowest degradation rate and longest calculated dwell time, which represents the length of time the foam is in contact with the vein, almost twice that of physician-compounded foams using room air and eight times better than physician-compounded foams prepared using equivalent gas mixes.

Conclusion: Bubble size, bubble size distribution and stability of various sclerosing foam formulations show that polidocanol endovenous microfoam results in better overall performance compared with physician-compounded foams. Polidocanol endovenous microfoam offers better stability and cohesive properties in a biomimetic vein model compared to physician-compounded foams. Polidocanol endovenous microfoam, which is indicated in the United States for treatment of great saphenous vein system incompetence, provides clinicians with a consistent product with enhanced handling properties.

Keywords: Foam drainage times; biomimetic analysis method; bubble size; bubble size distribution; foam half time; physician-compounded foams; polidocanol endovenous microfoam; polidocanol injectable foam; sclerotherapy; varicose veins.

Figure 1.

Methods for producing PCFs and PEM. In the DSS method, syringes are connected by a Combidyn® adapter (a), while in the Tessari method, they are connected by a three-way valve (b). In both techniques, the foam was produced by passing the polidocanol solution (liquid phase) from one syringe, 10 times into and out of the other syringe initially containing the gas or gas mixture (gaseous phase). Foam was produced at room temperature (20℃–22℃). The proprietary canister system for generating PEM (Varithena®) is shown in (c).

Figure 2.

Methods for measuring bubble size distribution. Sympatec QICPIC image analysis sensor (a) and Turbiscan™ LAB apparatus (b).

Figure 3.

Schematic of the biomimetic vein model set-up (a). Foam is injected into the tube over time t₁ to form a column of length x (mm) (b). On completion of the injection at x = L₁, the foam degrades over time t₂ to a length of x = L₂, whereby the DR and DT may be attained (c). CFAS: computational foam analysis system.

Figure 4.

Comparison of glass plate and Sympatec method analyses of polidocanol endovenous microfoam. (a) Image of PEM from the optical image analysis method and (b) bubble size distribution measured for this foam; compared to (c) a single frame image of the same sample of PEM captured from the Sympatec dynamic image capture method and (d) the bubble size distribution measured by this method (over a 15 s period, corresponding to 375 image frames). Note how the Sympatec over-reports the true bubble size.

Figure 5.

Size distributions of physician-compounded foams (DSS vs. Tessari) with liquid:gas ratio 1:7, obtained using the Sympatec method. Bubble size distribution curves for PCFs using different gas formulations (a + d RA; b + e: O₂:CO₂ of 35:65; c + f 100% CO₂) for both the DSS and Tessari methods 40 s and 115 s after foam preparation. Arrows highlight existence of larger bubbles in the PCF (n = 5). RA: room air.

Figure 6.

Comparison of bubble size distributions at 40 s and 115 s for PEM (a) compared to PCF O₂:CO₂ (65:35) made by DSS (b) and Tessari (c) methods. Arrows highlight existence of large bubbles in the foam (n = 5).

Figure 7.

Example foam drainage time curves used to measure FDT (a); FDT for DSS versus Tessari, and compared with PEM (b); FDT for different PCFs made using the DSS method at 1:4 and 1:7 liquid to gas ratios, and compared with PEM (c). Standard deviation ranged from 0.37% to 5.58% of the mean (n = 4). RA: room air; PEM: polidocanol endovenous microfoam; FDT: foam drainage time.

Figure 8.

Comparison of the foam half time (Turbiscan™) for various PCF formulations made using DSS and Tessari methods (1:7 liquid:gas ratio) and foam half time for PEM. PEM displayed a longer FHT than CO₂-containing PCFs (n = 5). FHT: foam half time; RA: room air; PEM: polidocanol endovenous microfoam.

Figure 9.

PEM had the longest calculated DT, almost twice that of PCFs using RA and approximately eight times better than PCFs prepared using equivalent gas mixtures in a biomimetic model (n = 4). RA: room air; PEM: polidocanol endovenous microfoam.