Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 581

11.6.3 Prefilled Syringes
With the innovation of prefilled syringes (PFS)/injector pen, parenteral medica-
tion becomes quite easy and patient friendly. It relieves the patient from the burden
of carrying syringes and vials of the protein drugs for either regular/chronic use or
for emergency situations. The major objective behind the idea of PFS is to cover the
needs of diabetic patients, that is, for insulin administration, but their versatility in
application has made them available for other P/P drugs also. The applicability of the
device includes safety and convenience, minimization of medicament, handling and
reduction of dosage errors and waste, and improved product sterility and stability.
They can be filled with disposable drug cartridges, have a built-in dosing meter and
a disposable needle tip, and allow for convenient penlike transport by the patient for
multiple administrations.
Most known PFS include an elongate syringe “cartridge” or “barrel” comprising a
cylindrical glass or plastic container in which the medicament or a component thereof
is prefilled; other components of PFS are piston (sizes 0.5-20 ml), tip caps, needle
shields (1/2, 5/8, 1 in.), rigid needle shield (1/2, 5/8, 1 in.). Needle shields are generally
made up of thermoplastic elastomers. Due to its handy portability, this system is much
more prone to exposure to higher temperatures and disturbances as compared to con-
ventional P/P drug formulations; hence, suitable stress testing has to be performed to
ensure stability under these conditions. Some areas that require manufacturers' atten-
tion regarding PFS are reduction in heavy metals and provision for a diluent syringe for
lyophilized powders. As siliconization of the glass barrel's inner side and the plunger
stopper is essential for the functionality of the syringe, a process that allows silicon
to be “baked” onto the inside of the syringe, preventing the formulation of free sili-
cone in P/P drug-containing solution, thus maintaining stability of the drug within the
device and lubrication of the plunger within the barrel are a few more aspects requir-
ing attention of manufacturer. Thorough understanding of the shape of PFS and related
performance problems such as, breakage, chippage, and defects will surely increase
the ultimate user benefits and manufacturers' sale. Modification in these areas with the
advancement of technology has truly increased the demand of PFSs [426-430] .
One example of a plastic PFS for a peptide drug product is the Daikyo Crystal
Zenith (CZ) syringe; a similar device for PEG interferon therapy in the treatment
of chronic hepatitis C is Redipen™, consisting of PEG intron powder, a dosing pen
with a dial-up dosing button for individualized weight-based dosing, and a small nee-
dle size (30G) to minimize patient discomfort. Another PFS, PEGASYS, was found
to be more user-friendly than Redipen™ [431] . Some of the categories of drugs
packaged in PFSs are vaccines, blood stimulants, therapeutic proteins, EPO, and
interferons [432] .
11.6.4 Needle-Free Injections
Needle-free injection systems have introduced new ways to administer various medi-
cines into patients without piercing their skin with a conventional hypodermic nee-
dle. This technology was first described in the nineteenth century in France, when