Development and Evaluation of Self emulsifying Drug delivery system of Lercanidipine HCI to improve dissolution in Biorelevant Media

Abstract

Lercanidipine HCl (LCH) is poorly water soluble anti-hypertensive drug. It is highly lipophilic (LogP = 6.4) and exhibit variable bioavailability as low as 10% when given orally. To overcome the dissolution issue, Self-emulsifying drug delivery systems were prepared. The lipidic excipients were grouped according to the fatty acid chain length in their structures as long (LC), medium (MC) and short (SC) chain glycerides. An extensive quantitative solubility studies and pseudo-ternary phase diagrams were conducted. Three formulations i.e. LC-SNEDDS, MC-SMEDDS and SC-SMEDDS were developed and characterized for self-emulsification time, % transmittance, globule size, zeta potential and in-vitro drug release. To conclude the best formulation among the three, drug release in biorelevant media and in-vitro lipid digestion studies were employed. Two way ANOVA was conducted to see the effect of dissolution medium and type of formulation on drug release. Finally, the optimized formulation was used for prediction of in-vivo absorption from the in-vitro release data in biorelevant media. The LC-SNEDDS contained ricebran oil: GMO (1:9) as oil phase, tween 80 and propionic acid as surfactant and co-surfactant respectively. The MC-SMEDDS was made up of Capmul MCM as oil phase and Cremophor RH 40 with PEG 400 as surfactant and co-surfactant respectively. Whereas SC-SMEDDS composed of triacetin as oil and tween 80 as surfactant without co-surfactant. The LC-SNEDDS resulted in a transparent (with bluish tinge) nanoemulsion after spontaneous process with globule size of as low as 8 nm. Zeta potential was found to be a positive value i.e. 14.3 mV due to presence of propionic acid. LC-SNEDDS released more than 80% drug release in all the tested dissolution media. However, two way ANOVA suggested that type of lipid formulation and different dissolution medium i.e. whether fasted or fed, had significant influence (p lt 0.05) on the % drug released. This finding proposed to be due to interplay of formulation derived lipid excipients and