Physicochemical characterisation of a drug-containing phospholipid-stabilised o/w emulsion for intravenous administration

Clomethiazole (CMZ) was used as a model drug to be incorporated into an emulsion vehicle. The effects of drug concentration and number of homogenisation steps were evaluated using multiple linear regression. The droplet size, measured as a z-average diameter by photon correlation spectroscopy (PCS),...

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Bibliographic Details
Published in:European journal of pharmaceutical sciences 2001-07, Vol.13 (4), p.393-401
Main Authors: Nordén, Tomas Petersson, Siekmann, Britta, Lundquist, Stefan, Malmsten, Martin
Format: Article
Language:English
Subjects:
1,2-Dipalmitoylphosphatidylcholine - chemistry
Anticonvulsants - chemistry
Biological and medical sciences
Chemical Phenomena
Chemistry, Physical
Chlormethiazole - chemistry
Clomethiazole
Coconut Oil
Dimyristoylphosphatidylcholine - chemistry
Drug–lipid interaction
Fat Emulsions, Intravenous
General pharmacology
Indicators and Reagents - chemistry
Injections, Intravenous
Magnetic Resonance Spectroscopy - methods
Medical sciences
Nuclear magnetic resonance
o/w emulsion
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Phospholipid
Phospholipids - chemistry
Photon correlation spectroscopy
Plant Oils - chemistry
Water
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Summary:Clomethiazole (CMZ) was used as a model drug to be incorporated into an emulsion vehicle. The effects of drug concentration and number of homogenisation steps were evaluated using multiple linear regression. The droplet size, measured as a z-average diameter by photon correlation spectroscopy (PCS), was found to be between 60 and 260 nm in the investigated range of CMZ concentrations, highly dependent on the concentration, but more weakly so on the number of homogenisation steps. Slow-scanning high-sensitivity differential scanning calorimetry (DSC) measurements showed that CMZ depresses the phospholipid chain melting temperature in the emulsion system, whereas 13C nuclear magnetic resonance (NMR) experiments suggested that the CMZ molecules are to a large extent located in the surface region of the emulsion droplets. This interpretation is compatible with results from NMR self-diffusion measurements, which showed that most of the CMZ molecules are rapidly exchanged between emulsion droplets and the aqueous surrounding. It can be concluded that the surface-active drug CMZ has a significant influence on the characteristics of phospholipid-stabilised emulsions through its ability to interact with the phospholipid interface. Thus, the results underline the importance of characterising drug–lipid interactions for the development of lipid-based formulations.
ISSN:0928-0987
1879-0720
DOI:10.1016/S0928-0987(01)00138-5