Sirolimus solid self-microemulsifying pellets: formulation development, characterization and bioavailability evaluation.

To enhance the dissolution and oral absorption of water insoluble drug sirolimus (SRL), self-microemulsifying pellets of SRL were developed and evaluated. Solubility test, self-emulsifying grading test, ternary phase diagrams and central composite design were adopted to screen and optimize the composition of liquid SRL-SMEDDS. The selected liquid SRL-SMEDDS formulations were prepared into pellets by extrusion-spheronization method and the optimal formulation of 1mg SRL-SMEDDS pellets capsule (1.0, 22.4, 38.4, 19.2, 121.6, 30.4 and 8.0 mg of SRL, Labrafil M1944CS, Cremophor EL, Transcutol P, MCC, Lactose and CMS-Na, respectively) was finally determinated by the feasibility of the preparing process and redispersibility. The optimal SRL-SMEDDS pellets showed a significant quicker redispersion rate than the dissolution rate of commercial SRL tablets Rapamune in water. The droplet size and polydispersity index of the reconstituted microemulsion was almost unchanged after solidification, and pellet size and friability were all qualified. Visual observation and scanning electron microscopic analysis confirmed good appearance of the solid pellets. DSC, XRPD, and IR analysis confirmed that there was no crystalline sirolimus in the pellets. Pharmacokinetic study in beagle dogs showed the oral relative bioavailability of SRL-SMEDDS pellets to the commercial SRL tablets Rapamune was about 136.9%. In conclusion, the solid SMEDDS pellets might be an encouraging strategy to improve the oral absorption of SRL and the extrusion-spheronization method was a feasible technology for the solidification of liquid SMEDDS.

Hu X ，Lin C ，Chen D ，Zhang J ，Liu Z ，Wu W ，Song H ... -  《-》

Optimized formulation of solid self-microemulsifying sirolimus delivery systems.

Cho W ，Kim MS ，Kim JS ，Park J ，Park HJ ，Cha KH ，Park JS ，Hwang SJ ... -  《International Journal of Nanomedicine》

Characterization and evaluation of self-microemulsifying sustained-release pellet formulation of puerarin for oral delivery.

The present study aims to develop self-microemulsifying drug delivery systems (SMEDDS) in sustained-release pellets of puerarin to enhance the oral bioavailability of puerarin. The performances of puerarin-SMEDDS including oils, emulsifiers, and co-emulsifiers were evaluated. Pseudo-ternary phase diagrams shows that the optimized formulation consisted of castor oil as the oil phase, Cremophor EL as the emulsifier, and 1,2-propanediol as the co-emulsifier. SMEDDS sustained-release pellets were prepared via extrusion-spheronization. The particle size distributions of the formulations were determined using transmission electron microscopy and scanning electronic microscopy. The mean particle size was 50 ± 8 nm. The pharmacokinetics and bioavailability of the puerarin-SMEDDS sustained-release pellets and puerarin tablets were evaluated and compared in beagle dogs. The absolute bioavailability of the puerarin-SMEDDS sustained-release pellets was enhanced by approximately 2.6-fold compared with that of the puerarin tablet. The relative bioavailability (F(rel)) of the SMEDDS pellets was 259.7% compared with the tablet group. The results demonstrated that the puerarin-SMEDDS sustained-release pellets had a sustained-release effect, and could remarkably improve the oral bioavailability of puerarin.

Zhang Y ，Wang R ，Wu J ，Shen Q ... -  《-》

Formulation optimization of solid self-microemulsifying pellets for enhanced oral bioavailability of curcumin.

Sha K ，Ma Q ，Veroniaina H ，Qi X ，Qin J ，Wu Z ... -  《-》

Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin, and absorption studies in rats.

This study describes the development and characterization of self-microemulsifying drug delivery systems (SMEDDS) in liquid and pellet forms that result in improved solubility, dissolution, and in vivo oral absorption of the poorly water-soluble compound curcumin. Solubility of curcumin was determined in various vehicles, including oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were constructed to identify the most efficient self-emulsification region. The optimized SMEDDS used for curcumin formulations in liquid and pellet forms contained 70% mixtures of two surfactants: Cremophor EL and Labrasol (1:1), and 30% mixtures of oil: Labrafac PG and Capryol 90 (1:1). The curcumin-SMEDDS in liquid and pellet formulations rapidly formed fine oil-in-water microemulsions, with particle size ranges of 25.8-28.8 nm and 29.6-32.8 nm, respectively. The in vitro rate and extent of release of curcumin from liquid SMEDDS and SMEDDS pellets was about 16-fold higher than that of unformulated curcumin. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with liquid and pelleted SMEDDS showed 14- and 10-fold increased absorption of curcumin, respectively, compared to the aqueous suspensions of curcumin. Curcumin-SMEDDS liquid and curcumin-SMEDDS pellets were found to be stable up to 6 months under intermediate and accelerated conditions. These studies demonstrate that the new self-microemulsifying systems in liquid and pellet forms are promising strategies for the formulation of poorly soluble lipophilic compounds with low oral bioavailability.

Setthacheewakul S ，Mahattanadul S ，Phadoongsombut N ，Pichayakorn W ，Wiwattanapatapee R ... -  《-》