Delivery Considerations of Highly Viscous Polymeric Fluids Mimicking Concentrated Biopharmaceuticals: Assessment of Injectability via Measurement of Total Work Done “WT”

Abstract

Abstract.An account is given of the recent development of the highly viscous complex biopharmaceuticals in relation to syringeability and injectability. The specific objective of this study is to establish a convenient method to examine problem of the injectability for the needle-syringe-formulation system when complex formulations with diverse viscosities are used. This work presents the inter-relationship between needle size, syringe volume, viscosity, and injectability of polymeric solutions having typical viscosities encountered in concentrated biologics, by applying a constant probe crosshead speed on the plunger-syringe needle assembly and continuously recording the force-distance profiles. A computerized texture analyzer was used to accurately capture, display, and store force, displacement, and time data. The force-distance curve and area under the curve are determined, and total work done for complete extrusion of the syringe content was calculated automatically by applying an established Matlab program. Various concentrations (i.e., 0.5-4% w/v of polymeric fluids/ dispersions) of polyethylene oxide (PEO) and hydroxypropyl methylcellulose (HPMC) with viscosity ranges of 5-100 cP mimicking concentrated monoclonal antibody solutions and complex biopharmaceutical formulations are investigated. Results indicate that calculated values of total work done to completely extrude the syringe content are the most appropriate parameter that describes viscosity-injection force of dispersed formulations. Additionally, the rheological properties of HPMC and PEO fluids in the context of syringeability and injectability are discussed.

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“…The injectability was discussed based on the determined values of dynamic glide force (DGF), the application of which is necessary to maintain the syringe plunger movement. Its value was determined on the basis of the average value of the longest range of forces in which they assume a constant value [ 31 ].…”

“…The effect of needle length was determined on the basis of tests carried out with the use of 23G needles with a length of 25 mm or 30 mm. The crosshead speed of 1 mm·s −1 was used, which is the most commonly used rate for manual injection [ 31 , 40 ].…”

“…The characteristic courses of the determined injection curves depend on the properties of the tested medium, especially its viscosity [ 9 , 29 , 30 ]. Based on the obtained experimental data, the following values are determined: the initial glide force (IGF) necessary to initiate the plunger movement, the dynamic glide force (DGF) necessary to maintain the plunger movement during injection, and the maximum force value recorded during the measurement [ 29 , 30 , 31 ]. Zhang et al [ 31 ], in their research, proposed to use the parameter called total work done as a quantity better than the above-mentioned forces describing the injectability process.…”

“…Based on the obtained experimental data, the following values are determined: the initial glide force (IGF) necessary to initiate the plunger movement, the dynamic glide force (DGF) necessary to maintain the plunger movement during injection, and the maximum force value recorded during the measurement [ 29 , 30 , 31 ]. Zhang et al [ 31 ], in their research, proposed to use the parameter called total work done as a quantity better than the above-mentioned forces describing the injectability process. Moreover, the use of instrumental injectability tests enables repeatable quantitative analysis, the results of which could be successfully correlated with panel tests [ 29 ].…”

“…So far, the results of injectability studies conducted for Carbopol [ 32 ], hyaluronic acid [ 33 ], shear-thinning hydrogels, (Hydroxypropyl)methyl cellulose (HPMC) and polyethylene oxide (PEO) [ 31 ] polymer solutions, immunoglobin solutions, monoclonal antibodies [ 34 ], protein systems [ 32 ], and other specific pharmaceuticals [ 9 , 35 ] have been published. In most of them, researchers focus mainly on determining the effect of substance concentration on its injectability process.…”