Development of a self-microemulsifying drug delivery system of domperidone: In vitro and in vivo characterization

Abstract

Domperidone, a dopamine D2 receptor antagonist, is used as a prokinetic and antiemetic agent for the treatment of gastroparesis, nausea and vomiting (1). It is a poor water soluble drug and is rapidly absorbed from the gastrointestinal (GI) tract. Its oral bioavailability was reported in a range of 13-17 % (2). Poor aqueous solubility and extensive first pass metabolism are the reasons for its low oral bioavailability. The approaches used to improve oral bioavailability were: incorporation of the active lipophilic component The main objective of this work was to prepare a self-micro emulsifying drug delivery system (SMEDDS) for enhancement of oral bioavailability of domperidone, a poorly water soluble drug. The solubility of the drug was determined in various vehicles. A pseudo ternary phase diagram was constructed to identify the self-micro emulsification region. The in vitro self-micro emulsification properties and droplet size analysis of SMEDDS were studied following their addition to water under mild agitation. Further, the resultant formulations were investigated for clarity, phase separation, globule size, effect of pH and dilutions (1:100, 1:500, 1:1000) and freeze-thaw stability. The optimized formulation, SMEDDS-B used for in vitro dissolution and bioavailability assessment, contained oil (Labrafac CC, 25 %, m/m), surfactant (Tween 80, 55 %, m/m), and co-surfactant (Transcutol ® , 20 %, m/m). The preliminary oral bioavailability of domperidone from SMEDDS was 1.92-fold higher compared to that of domperidone suspension in rats.The AUC 0-24 and c max values were 3.38 ± 0.81 µg h mL -1 and 0.44 ± 0.03 µg mL -1 for SMEDDS-B formulation in comparison with 1.74 ± 0.18 µg h mL -1 and 0.24 ± 0.02 µg mL -1 for domperidone suspension, suggesting a significant increase (p < 0.05) in oral bioavailability of domperidone from SMEDDSS.

Self-emulsifying drug delivery system and the applications in herbal drugs

“…As it described in Figure 2, SEDDS is an isotropic and thermodynamically stable solution consisting of oil, surfactant, cosurfactant and drug that can spontaneously form oil-in-water micro/nanoemulsion when mixed with water under gentle stirring. Owing to its miniscule globule size, the micro/ nanoemulsified drug can easily be absorbed through lymphatic pathways, bypassing the hepatic first-pass effect (Cho & Park, 2013;Jakki et al, 2013). The pathway of herbal drug transport from SEDDS is presented in Figure 3.…”

Formulation and Evaluation of Self-Nanoemulsifying Drug Delivery System Derived Tablet Containing Sertraline

“…The zeta potential, as well as polydispersity index, were measured employing a Malvern particle size analyzer (Nano ZS90, Malvern Instruments Ltd., Malvern, Worcestershire, UK). The optical clarity of the emulsion upon dilution was measured as percentage transmittance against double distilled as blank using UV-spectrophotometer (model UV-1800, Shimadzu Corporation, Kyoto, Japan) at 500 nm [36].…”

“…The friability of prepared formulations was determined by adding pre-weighed tablets in a Roche friabilator and was allowed to revolve (rotates at 25 ± 1 rpm) for one hundred times according to USP. The same tablets were weighed again after removing dust and calculated the percentage friability [36].…”

Self-Micro-Emulsifying Drug Delivery System to Enhance the Solubility of the Hydrophobic Drugs

“…This method is advantageous for the poorly water-soluble drugs with the lipid as vehicle and surfactants to form w/o micro emulsion within the GIT lumen. For example-Fexofenadine [3], domeperidone [4], danazol [5] etc.,…”