The Role of Particle Size Distribution on Bioavailability of Cyclosporine: Novel Drug Delivery System

Andrýsek, Tomáš

doi:10.5507/bp.2001.006

Cited by 3 publications

(1 citation statement)

References 8 publications

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“…As the first, physical aspect of novel highly available formulation was investigated gel formation upon contact with aqueous milieu 6,7 , which was associate with phase transition, when liquid crystalline phase is rising. In spite the fact that liquid crystalline phase has bio-adhesive character and mechanistic interpretation is thus offered, also character of individual excipients and theirs potential to affect bioavailability was considered 8,9 . Equoral ® , the second generation of product containing cyclosporin A developed in Opava contain besides active substance, ethanol and polyoxyethylated surfactant also polyglycerol esters.…”

Section: Introductionmentioning

confidence: 99%

Excipients and Their Role in Absorption: Influencing Bioavailability of Cyclosporine by Triglycerides and Polyglycerol Esters

Andrýsek¹

2006

BIOMED PAP

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Aims:The goal of the experiment was to verify bioavailability of immunosuppressive drug cyclosporine after oral administration, to determine, in particular, effect of triglycerides and polyglycerol esters on bioavailability of this lipophilic, poorly soluble drug.Methods: 1) Absorption of cyclosporine A from soya oil and polyglycerol-3-oleate was tested after intra-duodenal application to rats. This method enable to administer dispersion directly to the site of absorption and avoid problems with potential precipitation of active substances in the stomach. Samples were pre-dispersed in water and diluted on concentration 1mg/ml prior administration. In defined time intervals a blood sample was taken in a volume of 0.5 ml from the cannuled carotid. Blood was sampled in time 5, 15, 30, 45, 60, 90, 120, 180 and 240 minutes after application. For the comparison, Equoral ® oral solution diluted and pre-dispersed in the same manner was used. 2) 100 mg of cyclosporin in form of 1% dispersion in water was administered orally to dogs under fasting condition. The blood level of cyclosporine was evaluated from samples taken in time 0.5, 1, 1.5, 2, 2.5, 3, 5, 8, 12 and 24 hours following application. Formulations containing different ratio of polyglycerol esters / olive oil were compared.Results: The experiments conducted indicate that cyclosporine is 19× more available from polyglycerol-3-oleate than from soya oil. When applying cyclosporine in polyglycerol-3-oleate the average maximum blood level is 10x higher then in application of cyclosporine in oil. If polyglycerols are fully substituted with plant oils in the formula observed, its pharmacokinetic parameters decrease to 1/10 of the initial values.Conclusions: The right selection of a type of excipient accompanying cyclosporine affects significantly cyclosporine availability and thus its efficiency.

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Section: Introductionmentioning

confidence: 99%