Name: evaluation of drug sorption to pvc- and non-pvc-based tubes in administration sets using a pump
Uploaded: 2017-03-11T14:00:00
Description: Watch this Scientific Journal Video about Evaluation of Drug Sorption to PVC- and Non-PVC-based Tubes in Administration Sets Using a Pump at JoVE.com

This work was supported by the Korea Ministry of Environment (MOE) as part of the "The advancement of scientific research and technological development in environmental science program (E315-00015-0414-2)."

1. Preparation of Tubes in Administration Sets
NOTE: Precisely perform the cutting step to eliminate the effect of differences in tube length on drug sorption.
<ol>
	<li>Label the end of the tubes with the tube type (e.g., PVC, polyurethane (PU), and polyolefin (PO)) using a marker.</li>
	<li>Remove all detachable accessories, such as connectors and needle covers.</li>
	<li>Using a sharp razor to ensure clean edges, cut the tubes to 1 m in length from the connection of the drip cham...

<ol>
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A., Baker, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drug+compatibility+with+new+polyolefin+infusion+solution+containers.">Drug compatibility with new polyolefin infusion solution containers.</a> Am. J. Health Syst. Pharm. 63, 2379-2382 (2006).</li><li>Cloyd, J. C., Vezeau, C., Miller, K. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Availability+of+diazepam+from+plastic+containers.">Availability of diazepam from plastic containers.</a> Am. J. Hosp. Pharm. 37, 492-496 (1980).</li><li>Ceccherini, G., Perondi, F., Lippi, I., Grazia, G., Marchetti, V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intravenous+lipid+emulsion+and+dexmedetomidine+for+treatment+of+feline+permethrin+intoxication:+a+report+from+4+cases.">Intravenous lipid emulsion and dexmedetomidine for treatment of feline permethrin intoxication: a report from 4 cases.</a> Open Veterinary Journal. 5 (2), 113-121 (2015).</li><li>Lei, W., Yu, C., Lin, H., Zhou, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+tacrolimus-loaded+transfersomes+for+deeper+skin+penetration+enhancement+and+therapeutic+effect+improvement+in+vivo.">Development of tacrolimus-loaded transfersomes for deeper skin penetration enhancement and therapeutic effect improvement in vivo.</a> Asian J. Pharm. 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Drug sorption to administration sets is a cause of unexpected drug loss in intravenous drug delivery. During sorption, drugs are generally partitioned to polymeric materials of tubes at the early phase of infusion; after sorption equilibrium is reached, the delivered amount of drug is stabilized1. The sorption levels of drugs should be evaluated and minimized. Several evaluation methods for drug sorption have been studied, such as a pump method and a drip method. Compared to the drip method, the p...

Administration sets are composed of a spike, a drip chamber, tubes, Luer adapters (connectors), and a needle cover for protection. Other accessories, such as an airway check valve, a regulating clamp, an in-line filter, a Y-tube with cap (an injection port), and a needle, can also be attached to administration sets. Drug sorption to tubes is a critical issue in the delivery of injectable drugs1. Sorption describes the adsorption of a drug to the polymer surface and the absorption of a drug into the polymeric matrix2. Drug sorption to tubes in administration sets causes unpredictable drug loss and makes it difficult to control the delivered drug concentration. Drug sorption to polymeric tubes is therefore a major impediment to the precise transfer of injectable drugs into the body. However, there are no standard methods or regulatory guidelines for the evaluation of drug sorption to tubes in administration sets.
The levels of drug sorption to tubes in administration sets have been reported using various evaluation methods1,2,3,4,5. Test methods and model drugs are key factors in sorption evaluation. The pump method1,3 and drip method4,5 have been widely used for sorption tests. In general, the pump method should be used in the case of drugs with low concentrations and low flow rates as the infusion conditions. Using various evaluation methods, many studies of drug sorption have been reported for polyvinyl chloride (PVC)- and non-PVC-based tubes in administration sets1,2,3,5. Many sorptive drugs can be selected to investigate whether the tubes of the administration sets have drug sorption potential or not. Diazepam (Figure 1a)1, 2, tacrolimus (Figure 1b)5, nitroglycerin2, and cyclosporin A3 are representative drugs with high sorption in PVC- and non-PVC-based tubes.
For the evaluation of drug sorption to the tubes, test conditions such as flow rate and drug concentration are based on the clinical use of the selected drugs1, 6, 7. In the case of diazepam, a high concentration of 100 &#181;g/mL was used at a flow rate of 1 mL/min to mimic the initial dose for the treatment of status epilepticus1. For tacrolimus, a concentration of 10 &#181;g/mL was delivered at a flow rate of 10 mL/h. Dextrose solution (5%) was used for the dilution of drug injections, and tube length was fixed at 1 m. Glass bottles and vials should be used to prevent additional sorption during the experiment and storage.
In this study, we conducted a kinetic sorption study with the model drugs, diazepam and tacrolimus, using a pump method. Specific details of this protocol, from tube preparation to sorption evaluation, were described previously. Methods for the evaluation of drug sorption have already been used to confirm drug properties for injections and to recommend the clinical use of injections with administration sets on a case-by-case basis1,2,3,4,5,6,7. This protocol may be used as a standard technique for the sorption evaluation of administration sets. International standards for the evaluation of drug sorption to tubes may be necessary to ensure the safety and efficacy of drug delivery.

<table>
	<tbody>
		<tr>
			<td>PVC IV sets</td>
			<td>Becton Dickinson 
			(BD) Co. Ltd. (Franklin Lakes, NJ, USA)</td>
			<td></td>
			<td>Internal diameter: 2.54 mm</td>
		</tr>
		<tr>
			<td>PU IV sets</td>
			<td>Tianjin Hanaco Medical (THM) Co.Ltd. 
			(Tianjin, China)</td>
			<td></td>
			<td>Non-PVC 
			Internal diameter: 2.54 mm</td>
		</tr>
		<tr>
			<td>Non-PVC Polyolefin IV sets</td>
			<td>Polyscientech, Co. Ltd (Anseong, Korea)</td>
			<td></td>
			<td>Non-PVC [PE elastomer/PP elastomer/PB elastomer(25/50/25, weight ratio) blend] 
			Internal diameter: 2.54 mm</td>
		</tr>
		<tr>
			<td>Syringe</td>
			<td>Korea Vaccine Co. Ltd. (Seoul, Korea)</td>
			<td>KOVAX-SYRINGE 1 mL 26G 1/2&#34;</td>
			<td></td>
		</tr>
		<tr>
			<td>Daewon diazepam injection</td>
			<td>Daewon Pharma. Co. Ltd. (Hwaseong, Gyunggi, Korea)</td>
			<td></td>
			<td>1 mg/mL, total 2 mL 
			Batch No.: P003 
			Composition: diazepam, propylene glycol, ethanol, benzyl alcohol, sodium benzoate, bezoic acid, water for injection</td>
		</tr>
		<tr>
			<td>Tacrobel injection</td>
			<td>Chong Keun Dang, Co. Ltd. (Seoul, Korea)</td>
			<td></td>
			<td>5 mg/mL, total 1 mL 
			Batch No.: AG002 
			Composition: tacrolimus hydrate, polyoxyl 60 hydrogenated castor oil (HCO-60), dehydrated alcohol</td>
		</tr>
		<tr>
			<td>5% Dextrose</td>
			<td>JW Pharmaceutical (Seoul, Korea)</td>
			<td>500 mL</td>
			<td></td>
		</tr>
		<tr>
			<td>5% Dextrose</td>
			<td>Daehan Pharmaceutical (Seoul, Korea)</td>
			<td>200 mL</td>
			<td>Bottle (glass)</td>
		</tr>
		<tr>
			<td>Amber vials</td>
			<td></td>
			<td>20 mL</td>
			<td>Glass</td>
		</tr>
		<tr>
			<td>Terumo infusion pump</td>
			<td>Terumo (Medical Corp., USA)</td>
			<td>TE-135</td>
			<td></td>
		</tr>
		<tr>
			<td>HPLC system with UV detector</td>
			<td>Agilent (Santa Clara, CA, USA)</td>
			<td>Agilent 1260</td>
			<td></td>
		</tr>
		<tr>
			<td>CAPCELL PAK C18 column&#160;</td>
			<td>Shiseido (Japan)</td>
			<td>90404</td>
			<td>1.5 mm x 250 mm, 5 &#956;m</td>
		</tr>
		<tr>
			<td>Diazepam</td>
			<td></td>
			<td></td>
			<td>From Daewon Pharma. Co., Ltd.</td>
		</tr>
		<tr>
			<td>Tacrolimus</td>
			<td>Teva Czech industries&#160; (Czech Republic)</td>
			<td></td>
			<td>From Chong Keun Dang, Co. Ltd.</td>
		</tr>
		<tr>
			<td>Acetonitrile</td>
			<td>Burdick and Jackson Co., Ltd. (MI, USA)</td>
			<td>3/1/9017</td>
			<td></td>
		</tr>
		<tr>
			<td>Methanol</td>
			<td>Burdick and Jackson Co. Ltd. (MI, USA)</td>
			<td>AH230-4</td>
			<td></td>
		</tr>
		<tr>
			<td>Water</td>
			<td>Burdick and Jackson Co. Ltd. (MI, USA)</td>
			<td>3/1/4218</td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium dihydrogen phosphate</td>
			<td>Sigma (St. Louis, MO, USA)</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Phosphoric acid</td>
			<td>Sigma (St. Louis, MO, USA)</td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

evaluation of drug sorption to pvc- and non-pvc-based tubes in administration sets using a pump

Administration sets are delivery tools for the direct application of drugs into the body and are composed of a spike, a drip chamber, tubes, Luer adapters (connectors), a needle cover for protection, and other accessories. Drug sorption to tubes of administration sets is a critical issue in terms of safety and efficacy. Although drug sorption is an important factor in the quality of an administration set, there are no standard evaluation methods for the regulation of drug sorption to the tubes. Here, we describe an evaluation protocol for drug sorption to tubes of administration sets. Tubes made of polyvinyl chloride (PVC)- and non-PVC-based polymeric materials were cut to 1 m in length. Diazepam and tacrolimus were used as model drugs. In the kinetic sorption study, we selected the drug concentration and flow rate based on the clinical usage of these drugs. After the dilution of each drug in a glass bottle, the diluted drug solution was delivered through tubes of administration sets using a pump. Samples were collected in amber vials at appropriate time points and the drugs were analyzed using high-performance liquid chromatography. Drug concentrations and sorption levels to tubes of the administration sets were calculated. Acceptable criteria to ensure the quality of administration sets are recommended.

The sorption to tubes in the administration set was kinetically monitored using the model drugs, diazepam (Figure 1a) and tacrolimus (Figure 1b), and the pump method (Figure 2). Diluted drug (Figure 2a) was passed through PVC- and non-PVC-based tubes (Figure 2b) at a fixed flow rate using an infusion pump (Figure 2c). The glass bottle was opened slightly to allow the insertion of the admi...

Watch this Scientific Journal Video about Evaluation of Drug Sorption to PVC- and Non-PVC-based Tubes in Administration Sets Using a Pump at JoVE.com

Evaluation of Drug Sorption to PVC- and Non-PVC-based Tubes in Administration Sets Using a Pump

We report a method for drug sorption evaluation using a pump and model drugs (diazepam and tacrolimus). After drug analysis using high-performance liquid chromatography, drug concentrations and sorption levels in the tubes of administration sets are calculated.

Administration sets are delivery tools for the direct application of drugs into the body and are composed of a spike, a drip chamber, tubes, Luer adapters ...

The overall goal of this protocol is to evaluate the drug sorption of tubes in administration sets using an infusion pump. This method can help answer key questions in the quality evaluation field to help develop the tubes in administration sets suitable for injectable drug formulations. Though this method can provide insight into the sorption evaluation of drug to tubes in administration sets.It can also be applied to other systems, like accessorized tubes of administration sets. Demonstrating the procedure will be Dr.Su-Eon Jin, a research professor from my laboratory. To begin this procedure, label the tube type on the end of each tube.Then, remove all detachable accessories, such as connectors and needle coverings. Using a sharp razor, cut the tube to one meter in length from the connection of the drip chamber. Next, in labeled one liter glass bottles, dilute the drug injections with a five percent dextrose solution.Gently swirl the bottles to mix each drug solution. Transfer the diluted solution to an amber vial. It is important to mix the drug solution gently to prevent the generation of bubbles in bottles.First, confirm the tube depending flow rate using a pump, as outlined in the text protocol. Then, connect the end of one tube to a syringe. Immerse the other end in a bottled drug injection.Pull back on the syringe plunger until the tube is completely filled with drug solution. Next, open the door of the infusion pump and push the release lever. Insert the preloaded tube into the infusion pump.Removing the bubbles from tubes in administration sets is a required technique after loading the drug solution. After this, remove the syringe. Place a chemically-resistant borosilicate glass graduated cylinder over the end of the tube to collect the drug solution after it passes through.Set the flow rate, as outlined in the text protocol. Using amber vials, collect sample at room temperature at various time points. To begin, prepare standard drug solutions, as outlined in the text protocol.After this, inject ten microliters of each standard into an HPLC system with UV detection equipped with a C18 column. Confirm the specificity and linearity, and obtain calibration curves, as outlined in the text protocol. Next, dilute the drug samples as needed to fall within the calibration range.Directly inject ten microliters of each diluted sample into the HPLC system. Then, calculate the drug concentration and sorption level, as outlined in the text protocol. In this study, drug absorption to PVC and non-PVC based tubes were evaluated using a pump and model drugs.High performance liquid chromatography is then used to calculate drug concentrations and sorption levels in the tubes. A chromatogram of diazepam shows the drug peak at eight point two minutes, with interfering peaks that did not overlap. Sorption levels are then determined by calculating the percentage of remaining drug content after passage through the tubes.Sorption is seen to be the highest in PVC-based tubes, and lowest in PO based tubes, during the initial phase of the kinetic sorption test. The tacrolimus chromatogram shows a drug peak at six point eight minutes, with no interfering peaks. The determined sorption levels shows a similar trend with sorption being highest in PVC based tubes and lowest for PO based tubes.Once mastered, this technique can be done in one to four hours if it is performed properly. While attempting this procedure, it's important to remember to use glass-based containers, except on tubs of administration sets. After its development, this technique paved the way for researchers in the field of quality evaluation of administration sets, depending on the injectable drug formulations to explore physicochemical phenomena of drug sorption in tubes of administration sets during intravenous infusion.After watching this video, you should have a good understanding of how to perform a sorption kinetic study using a pump, and how to evaluate a drug sorption levels in tubes of administration sets. When the drug loss due to sorption in PVC-based tubes is found, we recommend using non-PVC-based tubes, such as polyolefin-based ones to minimize unwanted sorption.

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