Development and evaluation of nitrendipine loaded solid lipid nanoparticles: influence of wax and glyceride lipids on plasma pharmacokinetics.
Nitrendipine is an antihypertensive drug with poor oral bioavailability ranging from 10 to 20% due to the first pass metabolism. For improving the oral bioavailability of nitrendipine, nitrendipine loaded solid lipid nanoparticles have been developed using triglyceride (tripalmitin), monoglyceride (glyceryl monostearate) and wax (cetyl palmitate). Poloxamer 188 was used as surfactant. Hot homogenization of melted lipids and aqueous phase followed by ultrasonication at temperature above the melting point of lipid was used to prepare SLN dispersions. SLN were characterized for particle size, zeta potential, entrapment efficiency and crystallinity of lipid and drug. In vitro release studies were performed in phosphate buffer of pH 6.8 using Franz diffusion cell. Pharmacokinetics of nitrendipine loaded solid lipid nanoparticles after intraduodenal administration to conscious male Wistar rats was studied. Bioavailability of nitrendipine was increased three- to four-fold after intraduodenal administration compared to that of nitrendipine suspension. The obtained results are indicative of solid lipid nanoparticles as carriers for improving the bioavailability of lipophilic drugs such as nitrendipine by minimizing first pass metabolism.
Kumar
Venishetty Vinay
VV
University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh 506009, India; Pharmacology Division, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, Andhra Pradesh 500007, India.
Chandrasekar
Durairaj
D
Pharmacology Division, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, Andhra Pradesh 500007, India.
Ramakrishna
Sistla
S
Pharmacology Division, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, Andhra Pradesh 500007, India.
Kishan
Veerabrahma
V
University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh 506009, India.
Rao
Yamsani Madhusudan
YM
University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh 506009, India.
Diwan
Prakash Vamanrao
PV
Pharmacology Division, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad, Andhra Pradesh 500007, India. Electronic address: diwan@iict.res.in.
D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D005989:Glycerides / Q000737:chemistry; D007441:Intubation, Gastrointestinal; D008055:Lipids / Q000737:chemistry*; D008297:Male; D053758:Nanoparticles; D009568:Nitrendipine / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D010168:Palmitates / Q000737:chemistry; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical; D014280:Triglycerides / Q000737:chemistry; D014885:Waxes / Q000737:chemistry
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004337:Drug Carriers; D005989:Glycerides; D008055:Lipids; D010168:Palmitates; D013501:Surface-Active Agents; D014280:Triglycerides; D014885:Waxes; D020442:Poloxamer; C048159:glyceryl monostearate; C006957:cetyl palmitate; D009568:Nitrendipine; C005859:tripalmitin