Preparation and performance evaluation of saquinavir laden cationic submicron emulsions.
The main purpose of the present study was to investigate different cationic submicron emulsions as potential delivery for oral administration. Different submicron emulsion based formulations were prepared by standard procedures incorporating Chitosan, stearylamine, and protamine as charge inducer. Saquinavir (SQ) laden emulsions were characterized in terms of globule size, zeta potential, entrapment efficiency, release profile, cytotoxicity, LDH release, and stability studies. The prepared formulations were stable in terms of mean globule size, drug content, and tended to retain their cationic charge. Pay load efficiency was found to be pretty high (approximately 95-99%) in various formulations prepared. Sustained release phenomenon was more prominent in the case of chitosan emulsions (CE) followed by stearylamine emulsion (SE), Protamine emulsion (PE), and then plain emulsion (E) containing no charge inducer. The total amounts of drug released in 24 hr from CE, SE, PE, and E were 46%, 52%, 56%, and 62%, respectively. The induction of positive charge in emulsions resulted in enhanced absorption of drug through intestinal membrane. The apparent permeability coefficient through the intestinal sac was in the order of CE > SE > PE > E. The permeation flux of SQ through CE (1.0 microg/min) was more than twice compared to plain emulsion (0.46 microg/min) while it was almost three times (0.3 microg/min) compared to control. However, protamine based emulsion didn't confer significant improvement in absorption when compared to plain emulsion formulation. By this study it can be concluded that induction of positive charge on submicron emulsions can be effective for improving oral absorption of drug safely, as it is evinced with low LDH release into the medium when intestinal tissue is treated with submicron emulsion.
Jain
V
V
Pharmaceutics Division, Central Drug Research Institute, Lucknow, India.
Prasad
V
V
Jadhav
P
P
Mishra
P R
PR
D000284:Administration, Oral; D000588:Amines / Q000737:chemistry; D000818:Animals; D002412:Cations; D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D010316:Particle Size; D011479:Protamines / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D019258:Saquinavir / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D018675:Toxicity Tests
D000588:Amines; D002412:Cations; D003692:Delayed-Action Preparations; D004655:Emulsions; D005079:Excipients; D017320:HIV Protease Inhibitors; D011479:Protamines; D048271:Chitosan; D007770:L-Lactate Dehydrogenase; C009317:stearylamine; D019258:Saquinavir