SOLID LIPID NANOPARTICLES FOR CONTROLLED RELEASE PREPARED USING A MEMBRANE CONTACTOR
Multi-scale and/or multi-disciplinary approach to process-product innovation
Controlled Release of the Active Ingredient: Mechanisms, Devices & Analysis (T3-2P)
Keywords: controlled release, membrane, membrane contactor, nanoparticles, solid lipid nanoparticles
In recent years, it has become more and more evident that the development of new drugs alone is not sufficient to ensure progress in drug therapy. Solid lipid nanoparticles (SLN) were introduced at the beginning of the 1990s, as an alternative to solid nanoparticles, emulsions and liposomes in cosmetic and pharmaceutical preparations [1]. The SLN were realised by exchanging the liquid lipid (oil) of the emulsions by a solid lipid, which means lipids being solid at room temperature but also at body temperature.
The present study investigates a new process for the preparation of SLN using a membrane contactor, to allow large scale production [2]. The lipid phase is pressed, at a temperature above the melting point of the lipid, through the membrane pores allowing the formation of small droplets. The aqueous phase circulates inside the membrane module, and sweeps away the droplets forming at the pore outlets. SLN are formed by the following cooling of the preparation to room temperature.
The influence of process parameters (aqueous phase and lipid phase temperatures, aqueous phase cross-flow velocity and lipid phase pressure, membrane pore size) on the SLN size and on the lipid phase flux is investigated. It is shown that the membrane contactor allows the preparation of SLN with a lipid phase flux between 0.15 and 0.35 m3/h.m2, and a mean SLN size between 70 and 215 nm. Also, vitamin E loaded SLN are prepared. Their stability and their loading capacity are measured.
For example, the influence of the aqueous phase temperature on the SLN size and on the lipid phase flux is investigated. For temperatures below or equal to 60°C, the lipid phase flux is equal to 0.2 m3/h.m2. A slightly higher lipid phase flux is obtained at 70°C (0.26 m3/h.m2). The SLN sizes obtained for temperatures below the fusion point are smaller than those obtained for higher temperatures, around 70-80 nm. In this case, the lipid phase passes through the membrane pores and solidifies in the aqueous phase, which temperature is below the fusion point. For temperatures higher than the fusion point, the particle diameter decreases with increasing temperature, from 190 to 125 nm, for 50 to 70°C.
The advantages of this new process for the preparation of SLN are shown to be its facility of use, the control of the SLN size by an appropriate choice of process parameters and its scaling-up abilities.
References
[1] W. Mehnert, K. Mäder, Solid lipid nanoparticles, Production, characterization and applications, Adv. Drug Deliv. Rev. 47 (2001) 165-196
[2] C. Charcosset, A.A. El-Harati, H. Fessi, Preparation of solid lipid nanoparticles for controlled drug delivery using a membrane contactor, J. Controlled Release 108 (2005) 112-120
Please consider this abstract only for a POSTER PRESENTATION, thank you.
Presented Tuesday 18, 13:30 to 15:00, in session Controlled Release of the Active Ingredient: Mechanisms, Devices & Analysis (T3-2P).
