Preparation and Pharmacokinetics Evaluation of Solid Self-Microemulsifying Drug Delivery System (S-SMEDDS) of Osthole

Abstract

The study was performed aiming to enhance the solubility and oral bioavailability of poorly water-soluble drug osthole by formulating solid self-microemulsifying drug delivery system (S-SMEDDS) via spherical crystallization technique. Firstly, the liquid self-microemulsifying drug delivery system (L-SMEDDS) of osthole was formulated with castor oil, Cremophor RH40, and 1,2-propylene glycol after screening various lipids and emulsifiers. The type and amount of polymeric materials, good solvents, bridging agents, and poor solvents in S-SMEDDS formulations were further determined by single-factor study. The optimal formulation contained 1:2 of ethyl cellulose (EC) and Eudragit S100, which served as matrix forming and enteric coating polymers respectively. Anhydrous ethanol and dichloromethane with a ratio of 5:3 are required to perform as good solvent and bridging agent, respectively, with the addition of 0.08% SDS aqueous solution as poor solvent. The optimized osthole S-SMEDDS had a high yield (83.91 ± 3.31%) and encapsulation efficiency (78.39 ± 2.25%). Secondly, osthole L-SMEDDS was solidified to osthole S-SMEDDS with no significant changes in terms of morphology, particle size, and zeta potential. In vitro release study demonstrated a sustained release of the drug from osthole S-SMEDDS. Moreover, in vivo pharmacokinetic study showed that the T and mean residence time (MRT) of osthole were significantly prolonged and further confirmed that osthole S-SMEDDS exhibited sustained release effect in rabbits. Comparing with osthole aqueous suspension and L-SMEDDS, osthole S-SMEDDS increased bioavailability by 205 and 152%, respectively. The results suggested that S-SMEDDS was an effective oral solid dosage form, which can improve the solubility and oral bioavailability of poorly water-soluble drug osthole.

Premium ethylcellulose polymer based architectures at work in drug delivery

“…Initially, a liquid osthole loaded self-microemulsifying delivery system was formed and this was transformed into a solid form through the application of the spherical crystallization technique. Interestingly, the more stable solidified micro-emulsified system retained its initial morphology, particle size and zeta potential as when in the liquid state and ethylcellulose remained functional as a matrix former and release extender evidenced through the in vitro / in vivo studies (Sun et al, 2018). 51% w/w ethoxyl content ethylcellulose nanodispersions were prepared using a facile method involving its dissolution in ethanol and subsequent dipping in xanthan gum solution as an anti-solvent.…”

Development and characterization of phytosterol nanoemulsions and self-microemulsifying drug delivery systems

“…After 12 hours of dialysis(MWCO 500 Da), the SM was diluted with methanol for 10 times and demulsified by ultrasound for 30 minutes then W2 was determined by HPLC. The formula for determination of drug loading(DL) and entrapment efficiency (EE) are as follow [24]:…”

Development and characterisation of ibuprofen-loaded nanoemulsion with enhanced oral bioavailability

“…These systems offer an elegant approach for the delivery of poorly water-soluble drugs due to their self-emulsifying behavior. In addition, the small droplet sizes that is formed upon dispersion has been shown to improve drug absorption from the intestinal tracts [ 9 , 10 ].…”