This article is part of PharmTech's supplement "Injectable Drug Delivery."
More than two billion prefilled syringes are developed and used each year. The rise of the prefilled syringe as the preferred
container for injectable drugs began with Sanofi and Rhône-Poulenc Rorer's successful introduction of syringes for heparins
to the European market in the early 1980s. The prefilled syringe market has expanded considerably because of factors such
as the growth of biopharmaceuticals, the need to eliminate overfills, the need for precise delivery volumes, the desire for
convenient delivery, the quest for cost effectiveness, and the goal of reducing dosage errors (1–4).
Figure 1: Daikyo Crystal Zenith prefillable syringes (Daikyo Seiko, Tokyo). (IMAGES ARE COURTESY OF WEST)
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Currently, most prefilled syringes are made of glass, but plastic syringes are gaining popularity, particularly in applications
for which glass is an unsuitable delivery system. In the last decade, pharmaceutical protein and peptide drug products have
been approved for use with prefilled plastic syringes. One example is a peptide drug product in a Daikyo Crystal Zenith (CZ)
syringe (Daikyo Seiko, Tokyo) (see Figure 1). More products using plastic prefilled syringes are in various phases of drug
development.
The need for combination-drug delivery systems
Many chronic diseases such as multiple sclerosis and rheumatoid arthritis require the self-administration of injectable treatments.
This need has increased interest in combination-drug delivery systems that are safe, convenient, and help improve the administration
process.
Pen injectors and multidose cartridges were created for patients who need frequent injections. These devices were limited
to specific therapies such as diabetes and growth hormones, which often require weighed dosages or dose titration. Although
pen injectors were designed for frequent injections and for patients who require variable dose capabilities, they are not
ideal for chronic users of fixed-dose medications, including patients suffering from impaired dexterity. The need for a safe,
reliable, easy-to-use, single-dose injection system for these patients soon became apparent.
Figure 2: ConfiDose autoinjector (West, Lionville, PA). (IMAGES ARE COURTESY OF WEST)
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Autoinjectors have been recognized as a convenient method for delivering drug products through an intuitive activation mechanism
designed especially for patients whose poor dexterity affects their ability to inject a drug treatment effectively with a
traditional syringe (see Figure 2). As patients and caregivers become increasingly involved in determining the best treatment
option, biopharmaceutical, pharmaceutical, and device companies are adapting to meet consumers' needs.
Traditional systems' performance problems
Autoinjector systems traditionally use 1-mL glass prefilled syringes. These systems have been successful, but they have notable
limitations, including performance problems. Recent studies have shown that silicone oil, which is used to increase lubricity
in syringe systems, is often distributed unevenly, thus leaving certain areas of the prefilled syringe surface with insufficient
lubrication (5). The inconsistent silicone-oil coating can significantly affect the piston-travel and glide forces in autoinjectors.
In 2006, commercial lots of a drug product delivered by an autoinjector that contained a glass prefilled syringe were recalled
in several European countries because of problems with slow or incomplete delivery of the drug (6). Uneven silicone coating
may increase travel forces and cause failures such as incomplete injections.
