Syringeability and injectability are key-product performance parameters of any parenteral dosage form. The former refers to the ability of an injectable therapeutic to pass easily through a hypodermic needle on transfer from a vial prior to an injection, while the latter refers to the performance of the formulation during injection (1
). Syringeability includes such factors as ease of withdrawal, clogging and foaming tendencies, and accuracy of dose measurements. Injectability includes pressure or force required for injection, evenness of flow, and freedom from clogging (i.e.
, no blockage of the syringe needle). Syringeability and injectability concepts are of particular significance for specialized dosage forms, such as injectable emulsions, suspensions, liposomes, microemulsions, and microspheres. Over the last 15–20 years, these systems have become increasingly important in order to overcome issues specifically related to the drug solubility and stability, and achieve the desired rate of release (e.g.
, prolonged release after intramuscular or subcutaneous injection). Viscosity, density, flow are of paramount importance when considering such non-conventional formulations (2
Syringeability and injectability can be affected by the needle geometry, i.e.
inner diameter, length, shape of the opening, as well as the surface finish of the syringe (4
). This is of particular significance for self-injection devices, such as pens and auto-injectors, which are equipped with very thin needles. Indeed, patients can use pen injectors which employ 29–31-G needles. As far as pre-filled syringes are concerned, common needle configurations for subcutaneous dosing are 27 G and 25 G (4
). While reducing the pain of injection, fine needles require an increased force to inject the drug.
It is clear that both the ease of withdrawal of a product from a container (syringeability) and its subsequent injection into the intended administration site (injectability) must be determined for the finished drug product. Both parameters should be understood and characterized during product development.
According to the ICH Q6A Note for Guidance, parenteral formulations packaged in pre-filled syringes or auto-injector cartridges should have test procedures and acceptance criteria related to the functionality of the delivery system (6
). Moreover, in the FDA Guidance for Industry on container-closure systems for packaging human drugs and biologics, the evaluation of syringe's performance is required (7
). This should be addressed by establishing the force to initiate and maintain plunger movement down the barrel, and the capability of the syringe to deliver the labeled amount of drug product.
In spite of these regulatory requirements, no compendial testing procedures are specified in Pharmacopoeias. If difficulties in syringeability can be easily solved varying the needle size used in the withdraw procedure, in the meantime issues related to injectability can have a big impact on patient's adherence and, therefore, such parameter should be investigated.
In 1979, Ritschel and Suzuki (8
) proposed a method to determine injectability of parenterals by determining the time required to smoothly inject a solution, or suspension, into a meat sample under the specified pressure for a given syringe-needle system. In order to measure the force required to inject a liquid through a needle, a dynamometer (9
) or a micro-capillary rheometer connected to a dynamometer (11
) were also used. Eventually, the instrument developed by Chien et al
) was based on a constant nitrogen pressure, which moved a metallic punch, which was connected to the syringe plunger. These studies reported that injectability was related to both injection speed and product viscosity.
The current work aimed to propose a system of scoring the needle-syringe-formulation system in order to rationalize and support the selection of the optimal diameter and length of needles. Since measurement of injection force while the needle tip is exposed to air cannot sufficiently indicate the formulation's injectability in vivo, the extrusion testing was also carried out by inserting the needle directly in a human subcutaneous tissue model.