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

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.

A novel approach in the assessment of polymeric film formation and film adhesion on different pharmaceutical solid substrates.

The purpose of this study was to evaluate the nature of film formation on tablets with different compositions, using confocal laser scanning microscopy (CLSM), and to measure film adhesion via the application of a novel "magnet probe test." Three excipients, microcrystalline cellulose (MCC), spray-dried lactose monohydrate, and dibasic calcium phosphate dihydrate, were individually blended with 0.5% magnesium stearate, as a lubricant, and 2.5% tetracycline HCl, as a fluorescent marker, and were compressed using a Carver press. Tablets were coated with a solution consisting of 7% hydroxypropyl methylcellulose (HPMC) phthalate (HP-55), and 0.5% cetyl alcohol in acetone and isopropanol (11:9). The nature of polymer interaction with the tablets and coating was evaluated using CLSM and a designed magnet probe test. CLSM images clearly showed coating efficiency, thickness, and uniformity of film formation, and the extent of drug migration into the film at the coating interfaces of tablets. Among the excipients, MCC demonstrated the best interface for both film formation and uniformity in thickness relative to lactose monohydrate and dibasic calcium phosphate dihydrate. The detachment force of the coating layers from the tablet surfaces, as measured with the developed magnet probe test, was in the order of MCC>lactose monohydrate>dibasic calcium phosphate dihydrate. It was also shown that the designed magnet probe test provides reliable and reproducible results when used for measurement of film adhesion and bonding strength.