Physicochemical characterization and skin permeation of liposome formulations containing clindamycin phosphate.
This study was undertaken to evaluate the physicochemical properties and skin permeation of liposome formulations containing clindamycin phosphate (CP), especially when charge was imparted to the liposome. Five different liposome formulations were prepared using Phospholipon 85G (PL) and cholesterol (CH) by conventional lipid film hydration technique. Molar ratio of CH to PL was varied in the range of 0.16-1.0. Charged liposomes were prepared in the same way with addition of 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) and 1,2-dimyristoyl-sn-glycero-3-phosphate monosodium salt (DMPA) as charge carrier lipid for cationic or anionic charge of the liposome, respectively. Fresh full-thickness mice skin was taken and used for skin permeation study using Keshary-Chien diffusion cell with 1.77 cm(2) diffusion area at 37 degrees C. All liposome formulations prepared showed homogeneous size distribution with mean particle size of about 1 mum or less. Among the five liposome formulations prepared, formulation with the molar ratio of 0.5 showed the best result in the physicochemical properties such as polydispersity index, entrapment efficiency, size evolution, and ability of the liposome to retain CP as of entrapped in the vesicles. Charge-impartation of the formulation with cationic charge carrier lipid resulted in additional benefit in terms of inhibition of size evolution, the ability of the liposome to retain CP in the vesicles, and skin permeation. Steady state flux of the drug through the mice skin in the cationic liposome vesicles was 0.75 +/- 0.01 microg/cm(2)h while that in the control (dissolved into mixed alcohol solution) was 0.17 microg/cm(2)h. One half molar ratio of CH to PL was optimal in terms of physicochemical properties of the liposome formulation containing CP, and incorporation of cationic charge carrier lipid appeared to provide additional benefits for the stability of the liposome formulation and skin permeation of the drug.
Shanmugam
Srinivasan
S
College of Pharmacy, Yeungnam University, Kyungsan, 712-749, Korea.
Song
Chung-Kil
CK
Nagayya-Sriraman
Santhoshkumar
S
Baskaran
Rengarajan
R
Yong
Chul-Soon
CS
Choi
Han-Gon
HG
Kim
Dae-Duk
DD
Woo
Jong Soo
JS
Yoo
Bong-Kyu
BK
D000279:Administration, Cutaneous; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D002981:Clindamycin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004339:Drug Compounding; D004355:Drug Stability; D066298:In Vitro Techniques; D007700:Kinetics; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D010316:Particle Size; D010539:Permeability; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
D000900:Anti-Bacterial Agents; D008055:Lipids; D008081:Liposomes; D002981:Clindamycin; C007084:clindamycin phosphate