title: Investigation into the sorption of nitroglycerin and diazepam into PVC tubes and alternative tube materials during application.
abstract: Plastic bags and tubes are increasingly used for the storage and application of pharmaceutical formulations. The most common polymer material for drug application sets is plasticized poly(vinylchloride) (PVC). During application of pharmaceutical drug solution through PVC tubes, the polymer and the contact media interact which leads to leaching out of polymer additives or sorption of ingredients of the drug solution. Whereas the discussion of leaching of plasticizers is focussed on the toxicological properties of a drug packaging system, the sorption of drug formulation compounds has an influence on the dosage of the active pharmaceutical ingredient resulting in a reduced drug delivery to the patient. Therefore sorption has an influence on the effectiveness and success of the therapy. Within the study, the concentration profiles of nitroglycerin and diazepam solutions were determined after pumping the solutions through infusion administration sets. The study includes plasticized PVC tubes with different plasticizers (DEHP, DEHA, DEHT, TEHTM, DINCH, poly adipate), PVC (DEHP) tubes with different shore hardness as well as alternative polymer materials like EVA, TPE, PUR, silicone, LDPE and PP. From the experimental concentration curves it could be shown, that in the first minutes of the application of the drug solution the sorption of the active compound is at its maximum, resulting in the lowest concentration in the applied pharmaceutical solution. For a PVC tube with DEHP as plasticizer and a shore hardness of 80 only about 57% of the initial nitroglycerin concentration in the solution is applied to the patient in the first minutes of the application. For PVC tube (DEHP, shore 80) the experimental data were simulated using mathematical diffusion models. The concentration profiles during application could be well simulated using the partition coefficient K=50 (nitroglycerin) and K=300 (diazepam), respectively. However, the experimental results indicate, that the sorption of nitroglycerin into the PVC tube alters the diffusion behaviour of the polymer over flow time, which results in an increase of the diffusion coefficient during application. On the other hand, the other investigated alternative tube materials like PE or PP show a significantly lower sorption compared to PVC plasticizer systems. Due to the fact that the amount of sorption is varying over time, the concentration of the active pharmaceutical compound in the solution after passing the infusion administration set is not constant which makes the application of a constant concentration of a certain active ingredient to the patient very difficult. The simulated partition and diffusion coefficients for given PVC(DEHP) tubes were therefore used to simulate the initial concentrations profile of the feeding drug solution to assure a constant concentration flow profile after passing the administration set. The proposed methodology of this study represents a straight forward approach for the assessment of the drug sorption in dynamic flow systems based on experimental data as well as mathematical diffusion modelling. From the results a non-constant initial concentration profile for the active ingredient in a pharmaceutical drug solution can be established in order to compensate the loss of the pharmaceutical compound by sorption during infusion.
authors.affiliation: Fraunhofer Institute for Process Engineering and Packaging (IVV), Giggenhauser Strasse 35, 85354 Freising, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Treleano
authors.forename: Gerd
authors.initials: G
authors.lastname: Wolz
authors.forename: Rainer
authors.initials: R
authors.lastname: Brandsch
authors.forename: Frank
authors.initials: F
authors.lastname: Welle
mesh_terms: D000327:Adsorption; D003975:Diazepam / Q000008:administration & dosage / Q000737:chemistry*; D004051:Diethylhexyl Phthalate / Q000737:chemistry; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D007262:Infusions, Intravenous / Q000295:instrumentation; D008962:Models, Theoretical; D005996:Nitroglycerin / Q000008:administration & dosage / Q000737:chemistry*; D010968:Plasticizers / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011143:Polyvinyl Chloride / Q000737:chemistry*
chemical_list: D010968:Plasticizers; D011108:Polymers; D011143:Polyvinyl Chloride; D004051:Diethylhexyl Phthalate; D005996:Nitroglycerin; D003975:Diazepam