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用于局部应用的半固体SLN分散体:制剂和生产参数对粘弹性的影响。

Semisolid SLN dispersions for topical application: influence of formulation and production parameters on viscoelastic properties.

作者信息

Lippacher A, Müller R H, Mäder K

机构信息

Department of Pharmaceutics, Biopharmaceutics and Biotechnology, Free University of Berlin, D-12169 Berlin, Germany.

出版信息

Eur J Pharm Biopharm. 2002 Mar;53(2):155-60. doi: 10.1016/s0939-6411(01)00233-8.

Abstract

Aqueous solid lipid nanoparticle (SLN) dispersions with a high lipid content up to 35% and viscous to semisolid consistency were produced by a high pressure homogenization process. Despite their high lipid content and viscosity these dispersions preserved their colloidal size range. The SLN dispersions were compared to nanoemulsions and microparticle dispersions with regard to particle size, viscoelastic properties and formation of a semisolid gel structure. Viscoelastic measurements including oscillation stress sweep tests and oscillation frequency sweep tests demonstrated that the existence of a solid particle matrix with a particle size in the nanometer range is a prerequisite to form a semisolid dispersion having the appropriate consistency for topical application. Striking differences were observed between solid lipid micro- and nanodispersions of the same composition. Particle size reduction resulted in an 80-fold increase of the elastic modulus. Particle size distribution, the physical state of the dispersed lipid phase and the emulsifier concentration have been identified as further key factors for the viscoelastic properties and gel structure of the lipid nanodispersions. By conducting oscillation measurements it was possible to relate the stability of lipid dispersions to specific rheological parameters therefore providing a sensitive tool in stability assessment. Changing the production process from a 40 ml batch to a 2 l batch turned out to have an influence on the colloidal structures of semisolid SLN dispersions. Consistency increased but particle size and ratio of elastic to viscous properties stayed in the same range.

摘要

通过高压均质工艺制备了脂质含量高达35%且具有从粘性到半固体稠度的水性固体脂质纳米粒(SLN)分散体。尽管这些分散体脂质含量高且具有粘性,但它们仍保持其胶体粒径范围。将SLN分散体与纳米乳液和微粒分散体在粒径、粘弹性性质以及半固体凝胶结构的形成方面进行了比较。包括振荡应力扫描试验和振荡频率扫描试验在内的粘弹性测量表明,存在粒径在纳米范围内的固体颗粒基质是形成具有适合局部应用稠度的半固体分散体的先决条件。观察到相同组成的固体脂质微分散体和纳米分散体之间存在显著差异。粒径减小导致弹性模量增加80倍。粒径分布、分散脂质相的物理状态和乳化剂浓度已被确定为脂质纳米分散体粘弹性性质和凝胶结构的进一步关键因素。通过进行振荡测量,可以将脂质分散体的稳定性与特定流变学参数相关联,因此为稳定性评估提供了一种灵敏的工具。将生产工艺从40毫升批次改为2升批次,结果对半固体SLN分散体的胶体结构产生了影响。稠度增加,但粒径以及弹性与粘性性质的比率保持在相同范围内。

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