Abstract
Lipid based self nanoemulsifying drug delivery system (SNEDDS) was explored to improve the oral bioavailability of olanzapine (OLZ), a poorly water-soluble drug candidate, using spontaneous emulsification method. Nanoemulsions have ability to enhance the oral bioavailability of poorly water soluble or lipophilic drugs through selective lymphatic pathways. Following optimization, (from pseudo ternary phase diagram) OLZ SNEDDS consisting of Capryol 90(36.2%), Brij 97(14.6%) and ethanol (42.5%) were selected. The globule size (90 nm), and polydispersity index (0.287), was found to be minimum. The pharmacokinetic study was conducted on rabbits and the parameters like peak concentration (Cmax), time of peak concentration (Tmax), etc. were evaluated by Wagner nelson method. The in vivo studies concluded that there was 1.2 fold and 1.6 fold increase in bioavailability of nanoemulsion when compared with marketed tablet formulation and drug suspension, respectively. This may be attributed to increased solubility and enhanced permeability of the drug from nanosized emulsion. From the similarity factor between biorelevent dissolution media and 0.1 N HCl (pH 1.6) it was concluded that the 0.1 N HCl (pH 1.6) can be used for the dissolution of SNEDDS to predict the in vivo bioavailability instead of the biorelavent media. The level A correlation with correlation factor 0.97 was achieved, which showed that there is a good correlation between in vitro dissolution and in vivo bioavailability and the dissolution studies can be used as a surrogate for the in vivo studies.
Highlights
BCS Class II drugs suffer from poor water solubility and high lipophilicity resulting in a highly variable oral bioavailability
Lipid based drug delivery systems (LBDDS) are a diverse group of formulations which are classified into 4 types: Type I, Type II, Type III, Type IV
Solubility is an important criterion in formulation of Self Nano Emulsifying Drug Delivery Systems (SNEDDS), as the drug remains in the liquid form solubulized in the oil phase
Summary
BCS Class II drugs suffer from poor water solubility and high lipophilicity resulting in a highly variable oral bioavailability. The solubility of the drug could be increased in three ways: changing the chemical structure in the lead optimization phase; prodrug approach and the formulation approach. Formulation strategies such as micronization, co-solubulization, solid dispersion, inclusion complex, nanosuspension, lipid based formulations etc., may be employed to enhance their dissolution, thereby their bioavailability [1]. The drug in SNEDDS remains in the solution form throughout its GI transit time whereby they circumvent the dissolution step It involves digestion of the excipients and formation of different colloidal structures as nanodroplets. Research reveals that SNEDDS facilitates the transcellular and paracellular absorption thereby the drug is absorbed through the lymphatics via chylomicron sysnthesis of the fatty components of the oil phase of the emulsion [5]
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