Novel gels and their dispersions—oral drug delivery systems for ciclosporin

Murdan, Sudaxshina; Andrýsek, Tomáš; Son, Delphine

doi:10.1016/j.ijpharm.2005.06.002

Cited by 33 publications

(20 citation statements)

References 13 publications

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“…They have been tested with more or less success for the administration of inflammatory/analgesic drugs [7][8][9], cardiovascular drugs [4], antipsychotics [10] as well as nucleic acids [11] and peptides [12] by the transdermal, rectal, oral and buccal routes. In drug delivery, organogels are generally prepared using biocompatible and safe gelating molecules such as lecithin [8,[13][14][15], sorbitan monostearate (SMS) [4,12,16] and amino acid derivatives [17]. A promising avenue for organogels lies in their use as depot formulations following parenteral extravascular injection.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer’s disease

et al. 2010

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Organogels can be prepared by immobilizing an organic phase into a three-dimensional network coming from the self-assembly of a low molecular weight gelator molecule. In this work, an injectable subcutaneous organogel system based on safflower oil and a modified-tyrosine organogelator was evaluated in vivo for the delivery of rivastigmine, an acetylcholinesterase (AChE) inhibitor used in the treatment of Alzheimer's disease. Different implant formulations were injected and the plasmatic drug concentration was assayed for up to 35 days. In parallel, the inhibition of AChE in different brain sections and the biocompatibility of the implants were monitored. The pharmacokinetic profiles were found to be influenced by the gel composition, injected dose and volume of the implant. The sustained delivery of rivastigmine was accompanied by a significant prolonged inhibition of AChE in the hippocampus, a brain structure involved in memory. The implant induced only a minimal to mild chronic inflammation and fibrosis, which was comparable to poly(D,L-lactide-co-glycolide) in situ-forming implants. These findings suggest that tyrosine-based organogels could represent an alternative approach to current formulations for the sustained delivery of cholinesterase inhibitors.

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Section: Introductionmentioning

confidence: 99%

Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer’s disease

et al. 2010

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“…The gel-to-sol and/or sol-to-gel phase transition temperatures were measured using differential scanning colorimetry (DSC), as detailed below (Murdan, Andrysek, and Son 2005) and is presented in Table 3.…”

Section: Determination Of Phase Transition Temperatures (Tg) Of Amphimentioning

confidence: 99%

“…The endothermic peak on the DSC trace, corresponding to the gel-to-sol phase transition, was used to determine the phase transition temperature. A blank run where both cells were empty also was conducted under the same conditions to obtain a baseline (Murdan et al 2005).…”

Section: Determination Of Phase Transition Temperatures (Tg) Of Amphimentioning

confidence: 99%

Amphiphilic Gels as a Potential Carrier for Topical Drug Delivery

2007

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This study involves development of amphiphilic gels consisting solely of nonionic surfactants bearing cyclosporine and characterized for microstructure, gelation temperature, and in vitro drug release into dermis. The formulation is nonirritant and suitable for topical application. Gels consisting of cyclosporine were prepared using different methods by mixing the solid gelator (sorbitan or glyceryl fatty acid esters) and the liquid phase (liquid sorbitan esters or polysorbates) and heating them at 60• C to form a clear isotropic sol phase, and cooling this sol phase to form an opaque semisolid at room temperature. Gel microstructure was examined by phase contrast microscopy while gelation temperatures were measured by melting point apparatus and differential scanning calorimetry. These amphiphilic gels were evaluated in vitro for topical as well as transdermal delivery using rat skin mounted in a Franz diffusion cell. Gel microstructures consisted mainly of clusters of tubules of gelator molecules that had aggregated upon cooling of the sol phase, forming a 3D network throughout the continuous phase. The gels demonstrated thermoreversibility with robust gel network. At temperatures near the skin surface temperature, the gels softened considerably and moreover, it facilitated the drug to accumulate in dermis, thus making an ideal delivery vehicle of cyclosporine topically that can be used in treatment of psoriasis. Thus amphiphilic gels were demonstrated as the ideal vehicle for topical use of cyclosporine.

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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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Novel gels and their dispersions—oral drug delivery systems for ciclosporin

Cited by 33 publications

References 13 publications

Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer’s disease

Tyrosine-based rivastigmine-loaded organogels in the treatment of Alzheimer’s disease

Amphiphilic Gels as a Potential Carrier for Topical Drug Delivery

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

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