Increased norfloxacin skin permeability for fatty alcohol propylene glycol (FAPG) ointment by optimized process of preparation: behavior of stearic acid in stratum corneum lipids.
Preparation of the fatty alcohol propylene glycol (FAPG) ointment base plays an important role in controlling the physicochemical properties of ointments. These essay investigates the effects of preparative conditions such as cooling rate and stirring rate on the percutaneous absorption of norfloxacin from FAPG ointment. The influence of process-induced variation in enhancing effect of stearic acid which was incorporated into FAPG base was evaluated in vitro on rat skin. In the permeation experiment, norfloxacin penetration significantly increased with faster cooling rate. This result directly related to the increasing norfloxacin skin--vehicle partition coefficient. Histological analysis results showed no appreciable exfoliation of the stratum corneum. The differential scanning calorimetry (DSC) results show that stearic acid enriched lipid in the stratum corneum resulting from treatment with supercooling products may result in more crystalline structure and, hence preferential partitioning of the norfloxacin into the more crystalline regions of the membrane can be observed. A much greater enhancing effect can be achieved when we use stearic acid together with norfloxacin in propylene glycol (PG); but such effect cannot be found if 5 wt% stearic acid/PG suspension is used to pretreat skin before the application of norfloxacin PG solution.
Lin
H H
HH
School of Pharmacy, Kaohsiumg Medical College, Taiwan, Republic of China.
Hsu
L R
LR
Wu
P C
PC
Tsai
Y H
YH
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D000078404:Epidermal Cells; D004817:Epidermis / Q000737:chemistry / Q000378:metabolism*; D005233:Fatty Alcohols; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008297:Male; D009643:Norfloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009823:Ointment Bases / Q000737:chemistry*; D011409:Propylene Glycols; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects*; D012995:Solubility; D013229:Stearic Acids / Q000494:pharmacology*; D013696:Temperature
D000890:Anti-Infective Agents; D005233:Fatty Alcohols; D008055:Lipids; D009823:Ointment Bases; D011409:Propylene Glycols; D013229:Stearic Acids; C031183:stearic acid; D009643:Norfloxacin