Regulating particle morphology during a spray freeze drying ...

INTRODUCTION 11 IntroductionBiologically manufactured drugs represent a heterogeneous group of proteins andpeptides that resemble or imitate substances produced naturally in the body. Such drugsinclude monoclonal antibodies, fusion proteins, recombinant proteins, growth factors,angiogenetic factors and expression vectors [Boehncke and Radeke 2007]. The recentrisk of a possible pandemic H1N1‐influenza shows that biologicals are in great demand.The European Medicines Agency (EMEA) has been working on a crisis‐management plansince the outbreak of the “swine flu” pandemic in April 2009. A pandemic alert level wascalled by the WHO in the middle of 2009 [EMEA 2009]. It took just 6 months before 3different H1N1‐influenza vaccines received official approval throughout Europe by theEMEA.Usually vaccination is performed using a syringe and needle via injection of liquidinto the muscle tissue (im) or under the skin (sc). Another promising way forimmunization was reported by Chen et al. [2001; 2002; Osorio et al. 2003], the so‐called“epidermal powder immunization” (EPI). Influenza and hepatitis B antigen‐coated goldparticles were tested in mice. The particles were injected needle‐free with a specialdelivery device (PowderJect® device) powered by a small volume of compressed heliumgas. Vaccination under murine skin led to a high antigen concentration in the Langerhanscells with a cellular and humoral immune response.EPI offers some promising advantages over conventional injection with a syringeand needle. During powder injection there is no contact with blood, and the hazard oftransmission of contractible diseases is minimized. Compliance may increase, due to thelack of a cannula. Another advantage of dry powder usage is improved product stabilityduring storage and delivery compared to liquid formulations [Prestrelski and Burkoth1999].For effective vaccine delivery EPI‐powders must exhibit the necessary propertiesto penetrate the skin, i.e. adequate particle size, density and durability [Lahm and Lee2006]. A common method for manufacturing suitable powder particles is spray freeze‐