Nifedipine in semi-solid formulations for topical use in peripheral vascular disease: preparation, characterization, and permeation assay.
Nifedipine (NFD) has been used for the treatment of cutaneous lesions caused by peripheral vascular disease and diabetic ulcers. NFD was formulated at 8% in three semi-solid formulations: Polaxamer 407 Lecithin Organogel (PLO), PLO plus Transcutol(®), and an oil-in-water (o/w) emulsion. In vitro release and permeation tests were carried out using a synthetic (cellulose acetate) or natural membrane (pig ear skin), respectively, mounted in a Franz-type diffusion cell at 37°C in a constant water bath. As a receptor solution, isotonic phosphate buffer at pH 7.4 was used. All samples were analyzed by high-performance liquid chromatography by employing a previously validated method. The drug flow values were 6.126 ± 0.288, 4.030 ± 0.081, and 6.660 ± 0.254 μg/cm(2)/h for PLO, PLO plus Transcutol(®), and o/w emulsion, respectively. The three formulations did not show significant differences in drug flow, considering p > 0.05. Furthermore, their penetration profiles in both the epidermis and dermis were statistically different. Thus, the incorporation of NFD in PLO, PLO plus Transcutol(®), and o/w emulsion changed the drug thermodynamic activity, as expected. In addition, Transcutol(®) increased the solubility of NFD in the formulation and promoted its penetration in both the epidermis and dermis.
Medicines Department, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Ana Karla
AK
Santis
Zaida Maria Faria
ZM
de Freitas
Eduardo
E
Ricci-Junior
Lycia
L
de Brito-Gitirana
Laís Bastos
LB
Fonseca
Elisabete Pereira
EP
Santos
D000287:Administration, Topical; D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005782:Gels; D006863:Hydrogen-Ion Concentration; D054709:Lecithins / Q000737:chemistry; D009543:Nifedipine / Q000737:chemistry* / Q000493:pharmacokinetics; D016491:Peripheral Vascular Diseases / Q000188:drug therapy*; D010539:Permeability; D020442:Poloxamer / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D012995:Solubility; D013552:Swine
D002121:Calcium Channel Blockers; D005782:Gels; D054709:Lecithins; D020442:Poloxamer; D009543:Nifedipine