Researchers from France have reported a combined approach to study the adsorption of pharmaceutical ingredients onto soft PVC materials. Their results were published in the journal ACS Applied Polymer Materials.
To learn: Drug interactions with flexible PVCs. Credit: Toa55/Shutterstock.com
Medical uses of PVC: overview and problems
PVC possesses several beneficial properties that make it a commonly used material in industries such as construction, apparel, automotive, toy manufacturing and biomedicine. PVC is lightweight, has low manufacturing costs, is soft and recyclable. It is typically combined with up to 40% plasticizers to produce commercially viable materials with enhanced mechanical properties.
While this material has shown promise for medical device applications, its widespread medical use is hampered by plasticizers such as DEHP and phthalates. These plasticizers have potential carcinogenic, mutagenic, endocrine disrupting and reproductive toxicity problems. Because of this risk, the EU has restricted the use of DEHP in medical devices made from PVC, recommending alternative plasticizers.
Due to their small molecular size, plasticizers can interact with both the polymer matrix of medical devices and drug solutions. In addition, leaching and sorption can occur, resulting in adverse patient effects. Leaching can cause safety issues due to the potential toxicity or deterioration of the drug’s properties.
Sorption can compromise drug stability and potency through the loss of active pharmaceutical ingredients, resulting in decreased drug responses and difficulties in controlling the concentration of drug released. Drug-polymer interactions are a major issue in the delivery of drugs such as insulin and require further research in the pharmaceutical industry.
Gibbs free energy profiles calculated during the adsorption of paracetamol on a polyethylene surface. 5 Five independent calculations were performed to estimate the statistical standard fluctuations, which are of the order of 2–3 kJ mol−1. Photo credit: Sahnoune, M et al., ACS Applied Polymer Materials
understand sorption behavior
Studies have identified several factors affecting sorption in these materials. The chemical nature and properties of the polymer itself are an important contributing factor, along with the amount and type of plasticizers used. In addition, the physicochemical properties of the drug such as concentration, steric hindrance and lipophilicity play a role.
Other factors that determine sorption in medical devices using polymeric materials include excipient concentration and the infusion process. In recent years, several experimental methods have been developed to determine drug concentrations before and after passage through the medical device.
Recent advances in molecular modeling have improved the rationalization of experimental observations. Along with other advances in analytical methods, this has helped realize a bottom-up approach to linking chemical structures to desired material properties that limit sorption, additive loss, and drug degradation, which has so far proved a thorny endeavor.
A thorough understanding of drug sorption onto polymeric materials is crucial for designing more effective and safer drug delivery systems, combining experimental observations and advanced molecular modeling approaches. This helps researchers to understand adsorption phenomena at both macroscopic and microscopic levels.
Gibbs free energy profiles calculated during the adsorption of paracetamol on a polyethylene surface using the e-ABF and US methods. Photo credit: Sahnoune, M et al., ACS Applied Polymer Materials
The study
Based on the authors’ previous work, the study has proposed a combined and complementary approach to understand the sorption behavior of drugs on soft PVC materials in order to design better medical devices.
The authors have focused on two commonly used drugs: paracetamol and diazepam. First, the team designed high-performance liquid chromatography experiments to study the influence of the plasticizer on the adsorption of these drugs onto PVC tubing. The second step involved calculating the Gibbs free energy of the process in order to interpret the experimental results.
The research used advanced molecular simulations to correlate the sorption loss in the experiments with the Gibbs free energy of the process. Gibbs free energy calculations showed the strength of the interactions between the PVC surface and the drugs. A third step involved studying the interfacial region and drug mobility at the atomic level.
The study examined three plasticizers whose effect is comparable to that of PVC without additives: DEHT, TOTM and DINCH. The partition coefficient of paracetamol and diazepam was used to assess the quality of the molecular potentials.
The authors found that the octanol-water partition coefficient is a key property for elucidating drug-drug interaction information, and the reproduction of this property provides important evidence for the quality of the atomistic model.
Thermodynamic cycle with different free energy contributions a) free drug in water, b) adsorbed drug on water surface, c) free drug in cavity, d) adsorbed drug in cavity, where W, D and S refer to the water molecules, drug and .surface atoms. Photo credit: Sahnoune, M et al., ACS Applied Polymer Materials
study results
High performance liquid chromatography experiments showed that diazepam strongly adsorbs to soft PVC tubing but not to pristine PVC tubing. No discernible difference was observed for paracetamol. Simulations showed that adsorption is thermodynamically favored, with strong van der Waals interactions between drug and PVC material.
A threshold of -30 KJ mol-1 was confirmed by comparing experimental observations and simulations. Above this threshold, no significant drug loss by sorption was detected. The authors noted that simulations could energetically characterize sorption processes and help interpret the experimental results.
Atomistic descriptions of interface regions have been studied using molecular simulations. These descriptions are not possible through experimentation alone. The authors concluded that the simulations did not confirm absorption, only adsorption, as evidenced by a simulation time of hundreds of nanoseconds. PVC chain, plasticizer and water density profiles confirmed adsorption of the drug consistent with negative free energy of adsorption values.
The strongest free energy of the adsorption values corresponded to a slight slowdown in the mobility of the drug in both the direction perpendicular to the surface and in the plane parallel to the surface.
In summary, research has shown that this complementary approach can be used to characterize and interpret the adsorption behavior of drugs on soft PVC surfaces. The authors have stated that they hope this approach could be used in the future to develop improved PVC-based medical devices with reduced drug sorption.
Further reading
Sahnoune, M. et al. (2022) Drug interactions with flexible PVCs ACS Applied Polymer Materials [online] pubs.acs.org. Available at: https://pubs.acs.org/doi/10.1021/acsapm.2c00532
