Impact of different hydrophobic ion pairs of octreotide on its oral bioavailability in pigs.

The objective of this study was to investigate the impact of different hydrophobic ion pairs (HIP) on the oral bioavailability of the model drug octreotide in pigs. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate and docusate differing in lipophilicity. These hydrophobic ion pairs were incorporated in self-emulsifying drug delivery systems (SEDDS) based on BrijO10, octyldodecanol, propylene glycol and ethanol in a concentration of 5mg/ml. SEDDS were characterized regarding size distribution, zeta potential, stability towards lipase, log DSEDDS/release medium and mucus diffusion behavior. The oral bioavailability of octreotide was evaluated in pigs via LC-MS/MS analyses. Most efficient ion pairing was achieved at a molar ratio of 1:3 (peptide: surfactant). SEDDS containing the octreotide-deoxycholate, -decanoate and -docusate ion pair exhibited a mean droplet size of 152nm, 112nm and 191nm and a zeta potential of -3.7, -4.6 and -5.7mV, respectively. They were completely stable towards degradation by lipase and showed a log DSEDDS/release medium of 1.7, 1.8 and 2.7, respectively. The diffusion coefficient of these SEDDS was in the range of 0.03, 0.11 and 0.17×10-9cm2/s, respectively. In vivo studies with these HIPs showed no improvement in the oral bioavailability in case of octreotide-decanoate. In contrast, octreotide-deoxycholate and octreotide-docusate SEDDS resulted in a 17.9-fold and 4.2-fold higher bioavailability vs. CONTROL: According to these results, hydrophobic ion pairing could be identified as a key parameter for SEDDS to achieve high oral bioavailability.

Safety Assessment of Dialkyl Sulfosuccinate Salts as Used in Cosmetics.

The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) assessed the safety of 8 dialkyl sulfosuccinate salts for use in cosmetics, finding that these ingredients are safe in cosmetics in the present practices of use and concentration when formulated to be nonirritating. The dialkyl sulfosuccinate salts primarily function as surfactants in cosmetics. The Panel reviewed the new and existing available animal and clinical data in making its determination of safety. The Panel found it appropriate to extrapolate the data on diethylhexyl sodium sulfosuccinate to assess the safety of the entire group because all of the diesters are of a similar alkyl chain length, all are symmetrically substituted, and all have similar functions in cosmetic formulations.

Cytarabine-AOT catanionic vesicle-loaded biodegradable thermosensitive hydrogel as an efficient cytarabine delivery system.

Carrier with high drug loading content is one of the most important issues in drug delivery system. In the present work, an ion-pair amphiphilic molecule composed of anticancer drug cation and surfactant anion is used for straightforward fabricating vesicles for cancer therapy. Anticancer drug (cytarabine hydrochloride) and anionic surfactant (AOT) are selected for the fabrication of ion-pair amphiphilic molecule. One amphiphilic molecule contains one drug cation, thus the drug loading content is 50% (mol/mol) in theory. The in vitro drug release study shows that the release time of cytarabine is about 3 times of the pure cytarabine solution and the permeability of cytarabine has been improved about 160 times tested by parallel artificial membrane permeability assay model. However, the hemolytic toxicity is largely decreased in the studied concentration range. The in vitro cytotoxicity results show that cytarabine-AOT amphiphiles have a much lower IC50 (drug concentration resulting in 50% cell death) value and a higher cell inhibition rate comparing with their respective components, indicating its effective therapy for leukemic cells. To obtain a longer and a convenient drug release system, the prepared vesicles are further incorporated into the thermosensitive PLGA-PEG-PLGA hydrogel to prepare a subcutaneous administration. The in vivo drug release results indicate that cytarabine-AOT vesicle-loaded hydrogel is a good injectable delivery system for controlled release of cytarabine for cancer therapy.

Comparison of different intestinal epithelia as models for absorption enhancement studies.

In this study we compared the effect of two surfactants (laureth-6 and sodium docusate) on the permeability of a model hydrophilic drug across three different epithelia (Caco-2 cells, stripped porcine jejunum and rat ileo-jejunum). Among the tested epithelia Caco-2 cells are the tightest with the trans-epithelial electrical resistance of 372+/-4 Omega cm2 followed by porcine jejunum (124+/-8 Omega cm2) and rat ileo-jejunum (33+/-2 Omega cm2). Both surfactants decreased the trans-epithelial electrical resistance and increased the permeability of a model drug across Caco-2 cells at concentrations as low as 0.02 mg/ml, with more pronounced effect observed for laureth-6. On the other hand, ten times higher concentrations (0.2 mg/ml) did not affect the permeability of the model drug across the porcine jejunum. Similarly, laureth-6 at this high concentration had no effect on the trans-epithelial electrical resistance of the rat ileo-jejunum and did not increase the permeability of the model drug across this tissue. On the basis of these results we concluded that Caco-2 cells are much more sensitive to the investigated surfactants, that act as permeation enhancers, than the native intestinal tissues. Therefore, the results obtained in the experiments with Caco-2 cells might exaggerate the effects of the surfactants on the permeability compared to in vivo situation.

Microemulsions as topical drug delivery vehicles: in-vitro transdermal studies of a model hydrophilic drug.

Microemulsions with a 58:42 weight ratio of dioctyl sodium sulphosuccinate: octanol and containing 15, 35, and 68% water have been tested for their ability to transport glucose across human cadaver skin. A flow-through multisample skin diffusion cell showed that both the 35 and 68% water microemulsions caused enhanced (approximately 30-fold) transport of glucose. No transport was discernible for the 15% water microemulsion. Differences in percutaneous glucose transport were shown to parallel differences in the diffusion of water within the microemulsion vehicles before application to the skin.