Drug compatibility with a new generation of visiv polyolefin infustion solution containers

Drug Compatibility with a New Generation of VISIV
Polyolefin Infusion Solution Containers
Vasileios Aloumanis, MSFS
ABSTRACT
Michel Ben, MS
A new generation of VISIV polyolefin intravenous solution containers,
Thomas C. Kupiec, PhD
made of a new and different proprietary polymer, were evaluated for sorp-
tion and leaching potential with a cadre of drugs known to exhibit those
phenomena with polyvinylchloride containers. Sorption potential was
evaluated for amiodarone hydrochloride, carmustine, regular human in-
Lawrence A. Trissel, BS, RPh,
sulin, lorazepam, nitroglycerin, sufentanil citrate, and thiopental sodium.
Leaching potential was evaluated for tacrolimus and teniposide as well as
the vehicles of docetaxel and paclitaxel. Representative concentrations of
the drugs in infusion solutions or undiluted were placed into the new gen-
eration of VISIV containers and left in contact for up to 24 hours at room
temperature. High performance liquid chromatography was used to deter-
ACKNOWLEDGMENT
mine drug concentrations and the presence of plasticizer or other plastic
components, if any. Only regular human insulin exhibited any substantial
from Hospira, Inc., Lake Forest, Illinois. loss of concentration in the polyolefin containers that could be attributed
to sorption. Other drugs’ concentrations were consistent with their stabili-
ties over the test periods. No evidence of leaching of plasticizer or other
INTRODUCTION
plastic components was observed.
adsorption onto surfaces or absorption into polymer matrices, or leaching of plasticizer from plastic containers and tubing has been Materials
drug-free vehicles representing docetaxel, drugs making them incompatible with these paclitaxel, tacrolimus, and teniposide drug- plastic containers and administration sets.1 free vehicles were evaluated for leaching of A new generation of VISIV (Hospira, Inc., (Lot 54-063-JT; Hospira, Inc.) injections plastic components (Table 1). Acetonitrile, Lake Forest, Illinois) polyolefin infusion mercially. For the sorption portion of the nents were suitable for high-performance released using a new and improved propri- etary polymer from the original version. Although a previous study2 documented the compatibility of the earlier VISIV contain- ers, the compatibility of drugs that have regular human insulin (Lot SZF0177; Novo polyolefin plastic containers made of the to sorption or to leaching must also be de- Nordisk, Princeton, New Jersey), lorazepam new proprietary polymer for evaluation in termined for the new generation of VISIV (Lot 3922000; Hospira, Inc.), nitroglycerin this study were provided by Hospira, Inc.
containers manufactured from this new and (Lot 5116; American Regent Laboratories, Inc.), sufentanil citrate (Lot 101276; Akorn, Sample Preparation and Handling
The objective of this study was to deter- Inc., Buffalo Grove, Illinois), and thio- Sample solutions of each test admixture described in Tables 2 and 3 were prepared polyolefin infusion solution containers that Inc.) were obtained commercially. For the and were transferred into three of the new were made from the new and different pro- leaching portion of the study, diethylhexyl prietary polymer with seven drugs that have new polymer through the access port along with a control solution in a glass container. (PVC) containers and sets and an additional four drugs that have exhibited leaching of plasticizer or other polymer matrix compo- leaching plasticizer is associated with the exposed to fluorescent light while laying flat surfactants present in formulations (rather on laboratory counters to assure maximum 162 International Journal of Pharmaceutical Compounding
surface contact of the liquid contents. Samples for analysis were Table 1. Components for Drug-Free Vehicle evaluated for
taken from the access port using a needle and syringe initially and Diethylhexyl Phthalate Leaching.
after storage for 24 hours for all drugs except for carmustine. Due Component
Manufacturer
Lot Number
to its limited stability, the carmustine storage was evaluated for only HPLC Analysis
Each test solution was evaluated using HPLC. The Hewlett- N,N-Dimethylacetamide Spectrum Chemicala ND0084 Packard Series 1100 (Agilent Technologies, Palo Alto, California) consisting of a multisolvent delivery pump, autosampler, and photodiode array detector was used for analysis of the drugs. The system was controlled and integrated by a personal computer with Table 2. Drug Solutions evaluated for Sorption.a
chromatography management software (HPLC ChemStation Version A.09.03; Agilent Technologies). The specific parameters of each of the analytical methods for the drugs evaluated in the sorp- tion portion of the study are cited in Table 4. These methods were demonstrated to be stability indicating by accelerated degradation of the drug exposed to heat, 0.1 N hydrochloric acid, 0.1 N sodium hydroxide, and 3% hydrogen peroxide to intentionally degrade the subject drugs. The decomposition product peaks for each of the aAll drug solutions were prepared in 5% dextrose injection and evaluated over 24 drugs did not interfere with the peaks of the respective intact drugs.
hours contact time in the new VISIV polyolefin bags, except where noted otherwise.
The initial concentrations of the drugs were defined as 100%, Evaluated for only 6 hours due to inherent drug instability.
cPrepared in 0.9% sodium chloride injection.
and subsequent sample concentrations were expressed as percent- age of the initial concentration. Compatibility was defined as not less than 90% of the initial drug concentration remaining in the Table 3. Drug Solutions evaluated for Leaching of
Plastic Components.
The analyses for leached plastic components were performed Docetaxel vehicle equivalent to 0.74 mg/mL using an HPLC analytical method based on that of Waugh et al,3 Paclitaxel vehicle equivalent to 1.2 mg/mL with minor modifications to assure DEHP separation from the Tacrolimus vehicle equivalent to 0.02 mg/mL peaks of the drug product components. The liquid chromatograph Teniposide vehicle equivalent to 0.1 mg/mL Table 4. High-Performance Liquid Chromatographic Analytical Methods for Analysis of Drug Concentrations.
Parameter
Amiodarone Hydrochloride
Carmustine
a30% mobile phase B 0 minutes to 3 minutes, 90% mobile phase B 6 minutes to 9 minutes, 30% mobile phase B 9.1 minutes bMetacresol preservative eluted at 9.7 minutes. dBenzyl alcohol eluted at 3.3 minutes.
International Journal of Pharmaceutical Compounding
Table 4. (Continued)
Parameter
Lorazepam
Nitroglycerin
Sufentanil Citrate
Thiopental Sodium
Table 5. Drug Content Remaining in Test Solutions after
0.9999. The limits of quantitation and detection were 5.32 and 1.56 24-hour Contact Periods with the New VISIV Polyolefin
ng, respectively. The relative standard deviation from nine injec- Containers.
tions of DEHP for each drug admixture was 0.2% or less. Absence of detectable plastic components such as DEHP plasticizer was (% Remaining)
RESULTS AND DISCUSSION
Of the seven drugs tested that exhibited sorption to PVC, only insulin demonstrated a substantial loss in the new VISIV polyolefin containers (Table 5). About 45% of the insulin was lost after 24 hours. A control solution in a glass container exhibited a similar loss Carmustine exhibited about 10% loss in 6 hours, which is consistent with previous reports of the drug’s chemical instability,4-6 indicating that the new VISIV polyolefin container does not accel- erate carmustine decomposition or result in sorption. In addition, was also a Hewlett-Packard Series 1100 (Agilent Technologies). A a control solution in a glass container exhibited a similar loss of Phenomenex Luna C18 reverse-phase analytical column (Phenom- enex, Torrance California) was used, along with a guard column of Thiopental sodium concentration in the test samples declined the same material. The mobile phase consisted of methanol, water, about 5% in 24 hours, which is nearly identical to the loss that and glacial acetic acid (1800:198:2). The flow rate was 1.4 mL/min occurred in the thiopental sodium control solution in a glass bottle and the run time was 20 minutes. Sample injection volume was 10 in the same time period. This result again indicates that the new microliters for each of the drugs. Detection was performed at 225 VISIV container does not accelerate thiopental sodium decomposi- nm. The retention time for DEHP under these analytical condi- tions was about 7.5 minutes. The surfactant peaks did not interfere In this study of the new VISIV polyolefin containers, none of with the DEHP peak. The standard curve was over the range of the surfactant-containing vehicles for drugs that are known to 6.2 to 310 mcg/mL. The correlation coefficient was greater than leach plastic components, such as DEHP plasticizer from PVC 164 International Journal of Pharmaceutical Compounding
equipment,1,3,7,8 exhibited any leached components in the new poly- 10. Xu QA, Trissel LA. Compatibility of paclitaxel injection diluent olefin containers. This is consistent with previous research involv- with two reduced-phthalate administration sets for the Acclaim ing similar non-PVC devices and equipment.2,8-11 pump. IJPC 1998; 2(5): 382–384.
In 1968, Weisenfeld et al12 reported substantial loss of insulin 11. Faouzi MA, Dine T, Luyckx M et al. Leaching of diethylhexyl to infusion solution containers and administration sets. At least 35 phthalate from PVC bags into intravenous teniposide solution. additional published articles and research studies1 have also ad- Int J Pharm 1994; 105: 89–93.
dressed this sorptive loss of insulin. The previous studies that have 12. Weisenfeld S, Podolsky S, Goldsmith L et al. Adsorption of reported insulin adsorption to surfaces have reported losses as high insulin to infusion bottles and tubing. Diabetes 1968; 17(12): as 80%, but losses are more commonly cited as around 30% to 40% in a variety of glass and plastic container types.1 The current result indicates that insulin sorptive loss also occurs to the new VISIV Address correspondence to Lawrence A. Trissel, BS, RPh, FASHP, c/o polyolefin containers to an extent that is consistent with previous TriPharma Research, P.O. Box 265, Cashiers, NC 28717-0265. studies of a variety of container types as well as the former VISIV For drugs that are formulated using surfactants, the surfactants have been found to leach the plasticizer DEHP from PVC contain- ers and administration sets.3,4,7,8 The problem of plastic compo- nent leaching has extended to other types of plastic bags as well.9 However, no plasticizer leaching was found using the new VISIV CONCLUSION
Of the drugs tested, only insulin exhibited sorption to the new VISIV polyolefin containers. No leaching of plastic components such as plasticizer from the container was found with the vehicles of REFERENCES
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International Journal of Pharmaceutical Compounding

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