Development of nitrendipine controlled release formulations based on SLN and NLC for topical delivery: in vitro and ex vivo characterization.
The aim of the investigation is to develop solid lipid nanoparticles (SLN) and nano-structured lipid carrier (NLC) as carriers for topical delivery of nitrendipine (NDP). NDP-loaded SLN and NLC were prepared by hot homogenization technique followed by sonication, and they were characterized for particle size, zeta potential, entrapment efficiency, stability, and in vitro release profiles. Also the percutaneous permeation of NDPSLN A, NDPSLN B, and NDPNLC were investigated in abdominal rat skin using modified Franz diffusion cells. The steady state flux, permeation coefficient, and lag time of NDP were estimated over 24 h and compared with that of control (NDP solution). The particle size was analyzed by photon correlation spectroscopy (PCS) using Malvern zeta sizer, which shows that the NDPSLN A, NDPSLN B, and NDPNLC were in the range of 124-300 nm during 90 days of storage at room temperature. For all the tested formulations (NDPSLN A, NDPSLN B, and NDPNLC), the entrapment efficiency was higher than 75% after 90 days of storage. The cumulative percentage of drug release at 24 h was found to be 26.21, 30.81, and 37.52 for NDPSLN A, NDPSLN B, and NDPNLC, respectively. The results obtained from in vitro release profiles also indicated the use of these lipid nanoparticles as modified release formulations for lipophilic drug over a period of 24 h. The data obtained from in vitro release from NDPSLN A, NDPSLN B, and NDPNLC were fitted to various kinetic models. High correlation was obtained in Higuchi and Weibull model. The release pattern of drug is analyzed and found to follow Weibull and Higuchi equations. The permeation profiles were obtained for all formulations: NDPSLN A, NDPSLN B, and NDPNLC. Of all the three formulations, NDPNLC provided the greatest enhancement for NDP flux (21.485 +/- 2.82 microg/h/cm(2)), which was fourfold over control (4.881 +/- 0.96 microg/h/cm(2)). The flux obtained with NDPSLN B (16.983 +/- 2.91 microg/h/cm(2)) and NDPNLC (21.485 +/- 2.82 microg/h/cm(2)) meets the required flux (16.85 microg/h/cm(2)).
Bhaskar
Kesavan
K
Novel Drug Delivery Systems Laboratory, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh, India. bhaskurra@yahoo.com
Krishna Mohan
Chinnala
C
Lingam
Meka
M
Prabhakar Reddy
Veerareddy
V
Venkateswarlu
Vobalaboina
V
Madhusudan Rao
Yamsani
Y
D000279:Administration, Cutaneous; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004058:Diffusion; D004355:Drug Stability; D004356:Drug Storage; D066298:In Vitro Techniques; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D008297:Male; D053758:Nanoparticles; D009568:Nitrendipine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010316:Particle Size; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D013010:Sonication
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D008055:Lipids; D009568:Nitrendipine