Development of self emulsifying drug delivery system of itraconazole for oral delivery: formulation and pharmacokinetic consideration

Abstract

Poorly water-soluble drug, itraconazole (ITZ) offers a challenge in developing a drug product with adequate bioavailability. The potential for lipidic self-emulsifying drug delivery system to improve the oral bioavailability of ITZ was investigated in fasted rats. A series of ITZ SEDDS were prepared in three groups based on oil:S/CoS mixture ratios (1:9, 1:6 and 1:4) using Capryol 90 (oil), a mixture of Labrasol and Tween 20 (-surfactants) and Transcutol P (co-surfactant). The multicomponent delivery systems were optimized by evaluating their ability to self-emulsify when introduced in simulated gastric fluid, without pepsin, under gentle agitation and by determination of droplet size and visual observation. Three formulations (F5, F21 and F27), one from each group were selected based on droplet size and visual observation. The effect of oil and surfactants content on mean globule size of resulting emulsions was studied. It was clear that oil to surfactant and co-surfactant ratio has the main impact on the droplet size of the emulsion formed after dilution. However, the relation between droplet size and in vivo absorption of ITZ was futile. The order of AUC was 1:4 [ 1:6 [ 1.9 for oil:S/CoS mixture ratios. Following an oral administration of developed SEDDS and marketed capsule to rats, a 1.7, 2.0 and 2.33-fold increase in bioavailability was observed for F5, F21 and F27 respectively, compared with marketed capsule. The results from this study demonstrate the potential use of SEDDS to provide an effective way of improving oral absorption of lipophilic drugs.

Development of Solid Self-Emulsifying Formulation for Improving the Oral Bioavailability of Erlotinib

“…5g). Therefore, consistent with the DSC data, this result further confirmed the transformation of erlotinib into the amorphous state or molecular dispersion of erlotinib in the SEDDS formulations prepared with these carriers (28,34,35,44).…”

Approaches to Improve bioavailability and oral absorption of low water-soluble drug by self- emulsifying drug delivery system

“…Surfactant is one of the essential components in the formulation, as they promote the emulsification properties (during the preparation of SEDDS, SEDDS able to lower the interfacial tension to a very small value which facilitates dispersion process). Surfactants, being amphiphilic in nature, can dissolve (or solubilize) relatively high amounts of hydrophobic drug compounds [12,19]. The type and concentration of the surfactant showing effect on droplet size of micro-or nanoemulsion.…”

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“…There are reports of various attempts for improvement of solubility of itraconazole using techniques such as preparation of eutectic mixture, [13] phase inclusion complexes with β-cyclodextrin, [14] cocrystal, [15] solid dispersion using aerosol solvent extraction system, [16] self-emulsifying formulations, [17,18] nano-suspension, [19] nanoemulsions, [20] solid dispersion using high shear pelletization, [21] evaporative precipitation, [22] thin film freezing, [23] cogrinding, [24] and hot stage extrusion. [25] However, it should be contemplated that quite often increase in solubility of a drug also increases its rate of degradation.…”