Emergence of Prefilled Syringes
Natrajan Iyer, Chief Eng, VHB Medisciences, Bachlor Engg Technology & Purva Khot, QA Executive, VHB Medisciences, B Pharma Sci explain importance of Prefilled Syringes describing various components and testing methods.
Pre-filled disposable syringes (PFS) have gained wide acceptance as a preferred dosage form for administration of medicaments due to safety and convenience. They minimize handling of a medicament and reduce the dosage errors and contamination.
Many different types of pre-filled disposable syringes have been developed. 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 pre-filled.
The PSF are friendly, which may encourage patient compliance, especially for self –administered drugs (e.g. insulin) and a single PFS saves one unit operation of filling vials/ ampoules. PFS reduces wastage of pharmaceutical product. Switching to a PFS is not risk-free. The stability of drug within the device and lubrication of plunger within the barrel are risky.
Types of PFS
Currently there are different types of PFS available viz. Staked (in needle syringes), Luer (cone syringes); Luer lock syringes, Ready Ject syringes, and dual chamber syringes.
In order to make Prefilled syringes accessible to a wider range of pharmaceutical customers, presiliconised, pre-sterilized syringes were developed. They were presented in a tub and were ready to be filled. Buender Glas supported this trend by launching its RTF (Ready- To – Be- Filled) Syringes. The drug delivery system based on this container, together with a needle shield in the case of staked-in needle syringes, or a tip cap for the lock syringes, and a plunger stopper made from modern innovative rubber formulation. Finally, the system itself requires a plunger rod. For closing the syringe, rubber formulations covering the requirements of all relevant Pharmacopoeas (USP, EP, and JP) are available from the various procedures of pharmaceutical rubbers. In the case of plunger stoppers these units are available in standard configuration, gamma-sterilized in double bags.
Normally stoppers are modern latex free formulations available, which will be used for tip caps or needle shields as well as for stoppers. Needle shields are available in new innovative materials such as thermoplastic elastomers (TPEs).
The number of drugs that are only stable as a lyophilized powder, and must therefore remain in this form until just before administration, is increasing, especially for biotech drugs. For sophisticated drug delivery, pre-filled Diluent syringes have become an option. The volumes of most Diluent syringes used range from 0.5-5 ml.
Many of the recently developed drugs – especially into the area of biotech—have shown an increased sensitivity towards free silicon. However, 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’ on to the inside of the syringe, preventing the formulation of free silicone in the formulation of free silicone in the drug containing solution.
Based on spraying an emulsion of medical grade silicon oil into the glass barrel. During the following heat treatment, low chain-length fractions of silicon oil evaporate and a given fraction of the silicon oil with longer chain length forms hydrogen bonds as well as covalent bonds with the glass. This process is available in standard Siliconization grades as well as in individual customer-specific versions in order to cover specific requirements.
Heavy metal reduction
Biotech drugs are sensitive to heavy-metal contamination in the glass syringes. Due to the temperature of the viscous glass, the tungsten pin becomes smaller with time as it releases ions into the viscous glass. This problem can be overcome by using Tungsten-free pins, which requires a specific handling of glass forming lines.
Parts of PFS
Plunger: It’s used for moving the stopper in downward direction to inject product into the body. The construction of plunger is normally a four-ribbed design. Material of construction is of thermoplastic but doesn’t play an important role because the plunger does not come in direct contact with the product.
Stopper: The stopper isolates the product from the atmosphere. It resembles piston of I.C. Engine without the piston rings in the slots, which are provided. The sealing between barrel and stopper will explode, if two rigid surfaces come in contact with one another. An inert and sterile flexible sealant between the stopper and barrel is used to seal the product. The stopper has to be placed horizontal or parallel to the mouth of barrel. This happens during process filling by equipment, which fills PFS.
Material of construction (MOC) stoppers: The demands placed on elastomers and vulcanizates by the medical sector are extremely high. They are made by Bromobutyl and Chlorobutyl, this comes under halogen butyl rubbers, that are suitable for sealing applications.
The properties of sealing materials
i. Low permeability to gases and vapors; ii. Excellent chemical and biological inertness; iii. Cure versatility; iv. Low vulcanization agent requirement; v. Resistance to sterilization (steam, radiation, ethylene oxide); vi. Good sealing and resealing properties; vii. Good fragmentation resistance during needle penetration; viii. Low toxicity; ix. Low water absorption; xi. Good color retention; xii. Good compability with pharmaceutical products (low extractables, low absorption of active material)
Barrel: As new applications are developed, so the demands to be met by pharma-glass as a packing material. Glass requirements and surface treatment: The essential requirements in the parenteral field are high hydrolytic resistance to the drug, high neutrality and chemical resistance. Sometimes the glass requires surface treatment either at the manufacturer or processor.
Siliconization: Coating the glass with silicone facilitates efficient emptying of contents and eliminates dosages errors or wastage. It is important for the lubricity of the closure system.
Immersion: The glass barrel is immersed in a silicone bath and then passed through a drying tunnel to bind the coating. The amount of silicon oil on the glass is critical for potential interaction with the drug and the exact physical adjustment and correct function of the closure system used. Glass processors mostly do not perform silicone immersion, so Siliconization must be performed during the washing process by the filler.
Critical analysis of sealing between rubber stopper / barrel: Siliconization of rubber stopper and barrel are done for two purposes: i. When force is applied during injector there is a smooth moment of stopper i.e. less pain to patient. ii. Sealing the micro abnormality present in glass and rubber stopper to have tight sealing. Objective (i) and (ii) are opposing each other. When rubber stoppers are introduced into the barrel, will have interference fit i.e. rubber stoppers are made marginally higher than bore of barrel and fittings are done by processing machine, which is used for filling.