Self-Nanoemulsifying Lyophilized Tablets for Flash Oral Transmucosal Delivery of Vitamin K: Development and Clinical Evaluation

Owing to limited solubility, vitamin K undergoes low bioavailability with large inter-individual variability after oral administration. This article aimed to prepare self-nanoemulsifying lyophilized tablets (SNELTs) for the flash oral transmucosal delivery of vitamin K. Twenty-one formulae of vitami...

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmaceutical sciences 2017-09, Vol.106 (9), p.2447-2456
Main Authors: El-Say, Khalid M., Ahmed, Tarek A., Ahmed, Osama A.A., Hosny, Khaled M., Abd-Allah, Fathy I.
Format: Article
Language:English
Subjects:
Administration, Mucosal
Administration, Oral
Adult
Antifibrinolytic Agents - administration & dosage
Antifibrinolytic Agents - blood
Antifibrinolytic Agents - chemistry
bleeding disorders
Drug Liberation
Emulsions - chemistry
Freeze Drying
hepatic dysfunction
human volunteers
Humans
lyophilized tablets
Male
Middle Aged
Nanoparticles - chemistry
Solubility
Tablets
vitamin K
Vitamin K - administration & dosage
Vitamin K - blood
Vitamin K - chemistry
Vitamins - administration & dosage
Vitamins - blood
Vitamins - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Owing to limited solubility, vitamin K undergoes low bioavailability with large inter-individual variability after oral administration. This article aimed to prepare self-nanoemulsifying lyophilized tablets (SNELTs) for the flash oral transmucosal delivery of vitamin K. Twenty-one formulae of vitamin K self-nanoemulsifying drug delivery systems (SNEDDS) were prepared using different concentrations of vitamin K, Labrasol, and Transcutol according to mixture design. The SNEDDS was loaded on porous carriers and formulated as lyophilized tablets. The release profile and the pharmacokinetic parameters of vitamin K SNELTs were evaluated in comparison with commercial tablets and ampoules on human volunteers. Results revealed that the optimized SNEDDS showed the smallest and most stable nanoemulsion globules. SNELTs were prepared successfully and showed substantial superiority drug release compared with the commercial tablets. Interestingly, SNELTs enhanced both rate and extent of vitamin K absorption as well as relative bioavailability (169.67%) in healthy subjects compared with the commercial tablets. SNELTs revealed promising no significant difference in the area under the curve compared with the commercial intramuscular injection. SNELTs enhanced dissolution and bioavailability that expected to have the strong impact on the efficiency of vitamin K in the prophylaxis and treatment of bleeding disorders in patients with hepatic dysfunction.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2017.01.001