Lyophilization of water-in-oil emulsions to prepare phospholipid-based anhydrous reverse micelles for oral peptide delivery.
A novel procedure for the preparation of hydrophilic peptide-containing oily formulations involving the freeze-drying of water-in-oil emulsions (FWE) is described. A mixture of an aqueous phase containing insulin and oil phase containing phosphatidylcholine was emulsified to prepare water-in-oil emulsions, which were subsequently lyophilized. Upon addition of oil, the lyophilates formed a clear oily solution which was considered as an anhydrous reverse micelle (ARM) system since it contained no water but 20-nm insulin nanoparticles, as revealed by dynamic light scattering. The 20-nm insulin nanoparticles, existing in a crystal form, were also contained in the lyophilates, as proved by scanning electron microscopy, small angle X-ray scattering and differential scanning calorimetry analysis. The drug release from the oily formulation of SPC/insulin (10:1) was slow and less than 12% of the total insulin was released after 24h. A significant reduction in the plasma glucose level of fasting diabetic rats after oral administration of insulin-containing ARMs confirmed the bioactivity of the drug and the potential usefulness of phospholipid-based oily formulations. Both the ARMs and lyophilates were stable and could be stored at 4 degrees C for at least 6 months. Thus, this simple FWE procedure is suitable for the solubilization of hydrophilic peptides in oil to produce stable products for therapeutic applications.
Wang
Ting
T
Department of Pharmacy, Jining Medical College, No. 669 Xueyuan Road, Sunshine City, Shandong Province 276826, China. twangcn@yahoo.com
Wang
Ning
N
Hao
Aijun
A
He
Xia
X
Li
Tiefu
T
Deng
Yingjie
Y
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D005612:Freeze Drying; D007328:Insulin / Q000008:administration & dosage; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D010455:Peptides / Q000008:administration & dosage*; D010743:Phospholipids / Q000737:chemistry*; D051381:Rats; D012542:Scattering, Radiation
D001786:Blood Glucose; D007328:Insulin; D008823:Micelles; D010455:Peptides; D010743:Phospholipids