In pharmaceuticals, a nanosuspension is a colloidal dispersion of a drug, usually in an aqueous vehicle. Oil in water nanosuspensions such as liposomes and emulsions are used for topical oral and injectable drug delivery. Typically, the diameter of particles in a nanosuspension is less than 1 μm.<br/><br/>Different manufacturing techniques have been developed to produce nanosuspensions used in sterile injectable drugs. These must be aseptically prepared prior to administration. Due to their properties and propensity to chemical and physical degradation, sterilization of injectable nanosuspensions prior to filling can be challenging. For nanosuspensions with a particulate species of smaller than 200 nm, sterilizing grade filtration can be employed. While in many cases it is effective, bacterial challenge filter validation studies with injectable nanosuspensions have shown a higher likelihood of bacterial recovery compared with other parenteral drug types. Furthermore, the adsorptive impact of a sterilizing grade filter on nanosuspensions has been reported. Consequently, a greater understanding of the sterile filtration of nanosuspensions is required so that appropriate decisions are made concerning the selection and validation of sterilising grade filters for such applications and to ensure the best selection of sterile filter technology and highest degree of process safety.<br/><br/>In the reported work, liposome (Lipoid S) and emulsion (MF59) formulations were manufactured under standard methods for use in sterile injectable drug formulations. Using various techniques, they were characterised in terms of size and size-distribution, zeta potential, viscosity, pH, optical density. Here we present (a) the manufacture of nanosuspensions and their scale up using integrated Pall Allegro Single Use technologies (b) the effect of different filtration conditions/parameters (pre-filtration, pressure/differential pressure) and nanosuspension characteristics (size/size distribution) on sterile filtration and (c) liposome transmission studies and outcomes for different sterilising grade membranes.

Understanding the sterile filtration of nanosuspensions

255th National Meeting (2018)

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