Design of self-microemulsifying drug delivery systems using a high-throughput formulation screening system.
OBJECTIVE
A high-throughput formulation screening (HTFS) system that enabled to rapidly and efficiently select self-microemulsifying drug delivery system (SMEDDS) formulations has been developed in our previous study. The purpose of this study was to investigate the applicability of the HTFS system to SMEDDS designs.


METHODS
A poorly soluble drug (Nilvadipine), an oil (Sefsol-218), 11 hydrophilic surfactants (HS), and 10 lipophilic surfactants (LS) were used. Formulations were prepared and SMEDDS formulations were chosen by the HTFS system. A HS with the largest number of SMEDDS formulations was selected. In the selected HS system, a LS with the largest number of SMEDDS formulations was selected. Formulations with minimum turbidity at each ratio of the selected HS/LS were chosen as optimized formulations.


RESULTS
A total of 2455 formulations were prepared and SMEDDS formulations were selected using the HTFS system. From the screening data, HCO60 was selected as a superior emulsifiable HS, and Plurol (PLUROL OLEIQUE CC497) was selected as a suitable LS to HCO60. Five optimized formulations were chosen from the HCO60/Plurol system. The formulations formed fine microemulsions (<33.6 nm) without phase separation and drug precipitation. These formulation designs were conducted using 600 mg of the drug at a rate of 400 formulations/person/day.


CONCLUSIONS
SMEDDS formulations could be rapidly and efficiently designed using the HTFS system.
Sakai
Kenichi
K
Production Engineering Department (Formulation Technology), Chugai Pharmaceutical Co., Ltd., Tokyo, Japan. sakaikni@chugai-pharm.co.jp
Yoshimori
Takayuki
T
Obata
Kouki
K
Maeda
Hiroyuki
H
D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry; D057166:High-Throughput Screening Assays; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D010316:Particle Size; D012371:Robotics; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry
D000959:Antihypertensive Agents; D004655:Emulsions; D008055:Lipids; D013501:Surface-Active Agents; C035100:nilvadipine; D009543:Nifedipine