Liposomes large-scale manufacturing

CHAPTER 15 Some approaches to large-scale manufacturing of liposomes... 

Relatively few articles have been published on the industrial manufacturing of liposomes (Fildes, 1981 Rao, 1984 Ostro, 1988 Van Hoogevest and Fankhauser, 1989 Martin, 1989). A large number of patents describing procedures for large-scale production of... 

There are a number of commercial homogenizers (e.g., Five-Star, Manton-Gaulin, and Rannie homogenizers) that operate on similar principles (namely, high shear forces and high liquid pressures). These are commonly used for manufacturing emulsions and are adaptable for particle siz< reduction of liposomes in large scale. 

Unfortunately, the number of commercial formulations is very limited, primarily because of stability and manufacturing problems encountered during large-scale production. The list includes Sandimmune Neoral (cyclosporine A Novartis AG, Switzerland), which contains a microemulsion preconcentrate and is available as soft gels and solutions. Sandimmune (cyclosporine A Novartis AG, Switzerland), which contains an emulsion preconcentrate, and lipid soluble vitamins. Both formulations of cyclosporine have self-emulsifying properties and spontaneously form an o/w microemulsion (particle size <0.15 pm) and an o/w emulsion, respectively in the aqueous fluids of the GI tract. Although the discussion concerning potential of liposomes, niosomes, microemulsions, and solid dispersions for oral delivery is outside the scope of this chapter, the interested reader is referred to recently published reviews on these topics. " ... 

Formulation and/or development of advanced drug-delivery systems such as microencapsulated molecules, transdermal patches, or liposomes are frequently accomplished in the laboratory. However, large-scale production of these dosage forms may be problematic because the same conditions of manufacture may not be attainable or desirable in the plant setting. Consultation with process development personnel during the finalization of the prototype development phase is one way of minimizing scale-up difficulties. 

For the formation of DRV liposomes entrapping solutes that are not sensitive to the conditions used for MLV and/or SUV preparation, it is possible to prepare drug containing liposomes in the initial step of DRV formation. This is particularly important if amphiphilic/lipophilic or in general substances with low aqueous solubility are to be entrapped. However, when there is interest to have a method that can be easily up-scaled for large batch manufacturing, this approach can be problematic. 

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