The Impact of Surfactant Composition and Surface Charge of Niosomes on the Oral Absorption of Repaglinide as a BCS II Model Drug.

BACKGROUND: Niosomes, bilayer vesicles formed by the self-assembly of nonionic surfactants, are receiving increasing attention as potential oral drug delivery systems but the impact of niosomal formulation parameters on their oral capability has not been studied systematically. The aim of this study was to investigate the impact of surfactant composition and surface charge of niosomes in enhancing oral bioavailability of repaglinide (REG) as a BCS II model drug. METHODS: Niosomes (13 formulations) from various nonionic surfactants having HLB in the range of 4-28 (Tweens, Spans, Brijs, Myrj, poloxamer 188, TPGS and Labrasol) were prepared and characterized concerning their loading efficiency, hydrodynamic diameter, zeta potential, drug release profile, and stability. The oral pharmacokinetics of the selected formulations were studied in rats (8 in vivo groups). RESULTS: The results revealed that type of surfactant markedly affected the in vitro and in vivo potentials of niosomes. The Cmax and AUC values of REG after administration of the selected niosomes as well as the drug suspension (as control) were in the order of Tween 80> TPGS> Myrj 52> Brij 35> Span 60≈Suspension. Adding stearyl amine as a positive charge-inducing agent to the Tween 80-based niosomes, resulted in an additional increase in drug absorption and values of AUC and Cmax were 3.8- and 4.7-fold higher than the drug suspension, respectively. CONCLUSION: Cationic Tween 80-based niosomes may represent a promising platform to develop oral delivery systems for BCS II drugs.

An Investigation into the Role of P-Glycoprotein in the Intestinal Absorption of Repaglinide: Assessed by Everted Gut Sac and Caco-2 Cell Line.

The present study aimed at exploring the potential of the P-glycoprotein (P-gp) transporters as a barrier to the repaglinide (REG) epithelial permeability. In-vitro intestinal absorption models, the everted gut sac, and Caco-2 cell line, were used to study the possible role of P-gp in intestinal transport of REG. In the everted gut sacs, apparent permeability coefficients showed cargo concentration dependency transport over the concentration of 40 µM, indicating involvement of a saturable mechanism in REG absorption (Papp were 1.23 × 10 -5 and 3.29 × 10 -5 at drug concentrations of 40 and 100 µM, respectively). Adding verapamil (100 µM), valspodar (5 µM) and ketoconazole (10 µM) significantly enhanced the permeability of REG across mucosal to serosal in the rat jejunum (P < 0.05) suggesting role of CYP 3A4 and/or efflux transporters in oral bioavailability of REG. However, the results of Caco-2 cell experiments indicated low efflux ratios (less than 2) and insignificant involvement of P-gp efflux pumps in REG intestinal transport. Given that Caco-2 cells do not express adequate level of CYP 3A4, the current study suggests that the presystemic metabolism by cytochrome P450 (and not ejection by P-gp) may play a significant role in limiting the oral absorption of REG in small intestine.

An investigation into the role of surfactants in controlling particle size of polymeric nanocapsules containing penicillin-G in double emulsion.

Preparation, characterization and drug release behavior of loaded polybutyl adipate (PBA) nanocapsules with penicillin-G are described here. The nanocapsules were produced using a double emulsion solvent evaporation technique, using dichloromethane as an organic solvent and Tween and Span as surfactants. In this process, a mixture of glycerin and water was used instead of the traditional stabilizer system in the preparation of double emulsion. The influence of surfactants on the property of nanocapsules was discussed in detail. The effects of Span and Tween to modify the size of the nanocapsules were different. The mean diameters of penicillin-G loaded nanocapsules ranged from 75 nm to 638 nm and were dependent on the types and content of the surfactants. The encapsulation efficiencies and drug release rates were also affected by the surfactants in the preparation process. It was found that the encapsulation efficiencies of penicillin-G enhanced up to 76.8% with the increase in Span and Tween contents. Increasing Span concentration as an inner surfactant results in the remaining of penicillin-G mostly sealed in the inner aqueous phase and increasing Tween concentration as the outer surfactant enhanced the viscosity of external water phase, which decreased the rate of penicillin-G diffusion from the inner water phase to the outer water phase. Interestingly, the in vitro drug release profiles exhibited a significant burst release, followed by a lag phase of little or no release. Penicillin-G loaded nanocapsules with low concentrations of both surfactants tend to have higher burst release. Under optimum formulation conditions, the encapsulation of penicillin-G can reach up to 60% and the burst release can also fall below 45%. In this case, the fact that the nanocapsules have only 130 nm diameter will be important.