title: Lacidipine self-nanoemulsifying drug delivery system for the enhancement of oral bioavailability.
abstract: Low bioavailability of Lacidipine (LD), an calcium channel blocker pose many challenges in the treatment of hypertension. The objective of this study was to formulate and characterize LD self-nanoemulsifying drug delivery systems (SNEDDS) to improve oral bioavailability of the drug. Formulations were evaluated for globule size, surface morphology, emulsification time, cloud point, drug content, in vitro dissolution, ex vivo permeation, stability and oral bioavailability studies. Captex 810D, TPGS, Tween-60, Transcutol P and PEG 400 was selected based on the solubility study results. The optimized SNEDDS readily gets nanoemulsified at 37 °C with droplet size of 41 nm when mixed with 200 times of its water. Transmission electron microscope photographs confirmed the spherical shape of the globules. In vitro dissolution of SNEDDS showed more than 80% of drug release within 15 min. The ex vivo permeation of LD from SNEDDS is 4.8- and 9-fold higher compared to pure drug in the absence and presence of verapamil respectively. The stability study of the SNEDDS confirmed no environmental effect on the physical nature and drug content. Oral bioavailability of SNEDDS is 2.5 times higher than marketed tablet. The results suggest that, the SNEDDS formulation can be used as a possible alternative for the traditional oral formulations of LD to improve its oral bioavailability.
authors.affiliation: Laboratory for Lipid Based Systems, Department of Pharmaceutical Technology, Anna University, BIT Campus, Tiruchirappalli, Tamilnadu, 620024, India. natesansubbu@gmail.com.
authors.forename: Natesan
authors.initials: N
authors.lastname: Subramanian
authors.affiliation: Laboratory for Lipid Based Systems, Department of Pharmaceutical Technology, Anna University, BIT Campus, Tiruchirappalli, Tamilnadu, 620024, India.
authors.forename: Shanmugam Palaniappan
authors.initials: SP
authors.lastname: Sharavanan
authors.affiliation: Laboratory for Lipid Based Systems, Department of Pharmaceutical Technology, Anna University, BIT Campus, Tiruchirappalli, Tamilnadu, 620024, India.
authors.forename: Ponnusamy
authors.initials: P
authors.lastname: Chandrasekar
authors.affiliation: Laboratory for Lipid Based Systems, Department of Pharmaceutical Technology, Anna University, BIT Campus, Tiruchirappalli, Tamilnadu, 620024, India.
authors.forename: Alagar
authors.initials: A
authors.lastname: Balakumar
authors.affiliation: Department of Chemistry, Centre for Surface Science, Jadavpur University, Kolkata, 70032, India.
authors.forename: Satya Priya
authors.initials: SP
authors.lastname: Moulik
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004095:Dihydropyridines / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D007408:Intestinal Absorption; D007583:Jejunum / Q000378:metabolism; D008297:Male; D010316:Particle Size; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004655:Emulsions; D005079:Excipients; C060285:lacidipine
keywords: Bioavailability; Cloud point; Emulsification time; Lacidipine