Systematic Development of Self-Nanoemulsifying Liquisolid Tablets to Improve the Dissolution and Oral Bioavailability of an Oily Drug, Vitamin K1.

Chunhong Gao,Meiyan Yang,Qian Jin,Wei Gong,Xiaoyang Chu,Lu Chen,Jiahui Yang,Yuli Wang,Yongtao Tong,Chunsheng Gao

doi:10.3390/pharmaceutics10030096

Chunhong Gao, Meiyan Yang + Show 8 more

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https://doi.org/10.3390/pharmaceutics10030096

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Journal: Pharmaceutics	Publication Date: Jul 18, 2018
Citations: 21	License type: CC BY 4.0

Affiliation: Henan University

Abstract

The purpose of this study is to improve the dissolution and oral bioavailability of an oily drug, vitamin K1 (VK1) by combination of self-nanoemulsifying and liquisolid technologies. The optimal liquid self-nanoemulsifying drug delivery systems (SNEDDS) formulation including VK1 (oil), mixture of soybean lecithin and glycocholic acid (surfactant) and Transcutol HP (cosurfactant) was obtained according to ternary phase diagrams and a central composite design. Based on compatibility, adsorption capacity and dissolution profile, liquid SNEDDS was then solidified on Fujicalin® to form solid SNEDDS by liquisolid technology and compressed directly with excipients into self-nanoemulsifying liquisolid (SNE-L) tablets. Uniform nano-emulsion suspension was formed rapidly when the SNE-L tablets disintegrated in dissolution media and higher drug dissolution was observed compared with the conventional tablets. The results of pharmacokinetic study in beagle dogs showed that the mean Cmax and the area under the curve of SNE-L tablets were remarkably higher than those of conventional tablets, which were consistent with the results of the in vitro dissolution. The relative bioavailability of SNE-L tablets and conventional tablets was approximately 200%. In conclusion, this combination method showed promise to improve the dissolution and oral bioavailability of oily drug vitamin K1.

Highlights

Vitamin K1 (VK1) is a type of oily drug that is given to treat or prevent excessive bleeding in people with insufficient VK1 or who have taken excessive coumarin anticoagulant medication [1]
To overcome these adverse reactions, a new formulation of VK1 which was called Konakion® MM was launched in 1991; Konakion® MM is based on mixed micelles of lecithin and glycocholic acid [3]
A self-nanoemulsifying drug delivery system (SNEDDS) enhances the oral bioavailability of hydrophobic drugs by avoiding the hepatic first-pass effect, reducing metabolism by the cytochrome-P450 family of enzymes, inhibiting P-glycoprotein (P-gp) efflux, and promoting drug transport via lymph circulation [7]

Summary

Introduction

Vitamin K1 (VK1) is a type of oily drug that is given to treat or prevent excessive bleeding in people with insufficient VK1 or who have taken excessive coumarin anticoagulant medication [1]. VK1 is mainly administered intramuscularly or intravenously; these routes have rapid effects, but they occasionally result in allergic reactions, anaphylactic shock, or hemolysis [2] To overcome these adverse reactions, a new formulation of VK1 which was called Konakion® MM was launched in 1991; Konakion® MM is based on mixed micelles of lecithin and glycocholic acid [3]. As a liquid formulation, inherent defects, such as, migration of the components, potential drug leakage, low stability during manufacturing, have limited its practical industrial application [8]. To overcome these difficulties, solid SNEDDS (S-SNEDDS) formulations have been investigated as an alternative approach

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