Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1995-06-23
1997-03-18
Page, Thurman K.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424488, 424455, A61K 914
Patent
active
056120583
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a lyophilized emulsion which can be redispersed with water to give the original emulsion.
In particular, the invention relates to a fat emulsion which contains an active substance and whose external aqueous phase has been removed by freeze-drying and which can be redispersed by addition of water spontaneously to give the original emulsion with a particle size distribution corresponding to the initial formulation.
Emulsions are disperse systems composed of two mutually immiscible liquids, one of which, the internal, disperse phase, is finely dispersed in the other, the external, continuous phase.
Fat emulsions are emulsion systems in which the internal, disperse phase consists of very fine fat particles which are homogeneously dispersed in the external phase which is composed of water. Emulsion formulations of this type are preferably used parenterally and are particularly used for intravenous nutrition of patients unable to take food by mouth.
Fat emulsions which can be administered intravenously make high demands on the tolerability of their ingredients and the particle size of the fat particles. Preferably used as fat component are oils with a high content of unsaturated fatty acids such as soya bean, safflower and cottonseed oils, as emulsifiers are lecithins such as egg, soya and cerebral lecithins, as well as antioxidants such as tocopherol acetate and other auxiliary substances.
The fat particles should, in order to avoid changes in blood pressure and the risk of embolism, not exceed an average particle size of 1 .mu.m.
The emulsion is normally prepared by preemulsifying the heated oil and aqueous phases with a mixer, followed by microfine emulsification using a high-pressure homogenizer and subsequent sterilization with superheated steam.
The "Handbook on Injectable Drugs" (American Society of Hospital Pharmacists, pages 237-244 (1986), Lawrence A. Trissel) describes some commercially available formulations. They contain soya bean oil or safflower oil, egg lecithin, glycerol and water and have average particle sizes of .ltoreq.0.5 .mu.m.
Fat emulsions are also repeatedly used as vehicle systems for lipophilic medicinal substances to be administered parenterally. The aim in this case is to increase the therapeutic efficacy and safety of medicinal substances by controlled release from emulsion systems.
In accordance with their solubility properties, lipophilic active substances in emulsions are partly or completely incorporated in the fat particles. This means that their pharmacokinetic behaviour is crucially determined by the pharmacokinetic behaviour of the vehicle formulations from which the active substance is first released. Delayed release avoids high local concentrations of active substance, reduces degradation and thus increases the duration of action.
Emulsion systems of this type are particularly advantageous for prostaglandins, especially prostaglandin E.sub.1 (PGE.sub.1). PGE.sub.1 is a highly active tissue hormone which is successfully used, for example, for the treatment of arterial occlusive disease. Used for this purpose is a PGE.sub.1 -.alpha.-cyclodextrin complex which, dissolved in physiological saline solution, is infused parenterally, preferably intraarterially, as close as possible to the body region to be treated. However, high pressure conditions and small dilution effects during the intraarterial infusion make high demands on the equipment and the training of the treating physician. Although intravenous infusion is simpler to perform by comparison, even in this case infusion is possible only slowly and in relatively high dilution because of the local irritant effect of PGE.sub.1. Overall, the extended residence time of the active substance in the vascular system before reaching the target site and, in particular, the additional passage through the pulmonary circulation leads to increased degradation of active substance. Both intra-arterial and intravenous infusions make high demands on the equipment and careful adjustment of the infusion rate a
REFERENCES:
patent: 5192549 (1993-03-01), Barenolz et al.
patent: 5407609 (1995-04-01), Tice et al.
Japan Abstract Freeze Dried oil-in-water Emulsion Prepn. #J60239417-A Nov. 28, 1985 (8603).
PCT International Search Report for PCT/DE 93/01188.
Emschermann Bernhard
Mika Hans-Jurgen
Schutz Andreas
Sievert Frank
Benston W.
Page Thurman K.
Schwarz Pharma AG
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