Substantivity of Sunscreen - "in vitro" evalutation of the transdermal permeation characteristics of some benzophenone derivatives

Synopsis The in vitro permeation through excised hairless mouse skin of a series of 4-O-(N, N-dimethylaminoalkyl)-benzophenones, non-quaternarized and quaternarized, and of two commercial benzophenone sunscreens, taken as reference compounds, was investigated. The aim of the study was to verify the skin penetration of the highly skin-substantive quaternary ammonium derivatives, in comparison with their parent, non-quaternarized compounds. While the quaternary derivatives proved unable to permeate the skin during the period of observation (45 h), their parent amine hydrochlorides and the reference sunscreens (2-hydroxy-4-methoxy-benzophenone-5-sulphonic acid and 2,2'-dihydroxy-4,4'-dimethoxy-benzophenone 5,5'-sodium disulphonate), showed appreciable transdermal fluxes. These data indicate that the presence of a quaternary ammonium group in a molecule, besides inducing a high affinity for cutaneous keratin, may result in hindered or reduced transdermal (and possibly systemic) absorption. Both features may contribute in improving the safety of a cosmetic sunscreen

Cytotoxicity of potential ocular permeation enhancers evaluated on rabbit and human corneal epithelial cell lines

A series of prospective ocular permeation enhancers. benzalkonium chloride (BAC), cetylpyridinium chloride (CPC), ethylenediaminetrtraacetic acid (EDTA), polyoxyethylene (20) stearyl ether (PSE) and polyelhoxylated castor oil (PCO) were tested for cytotoxicity on cultures of rabbit (RCE) and human (HCE) corneal epithelial cells. The cells were treated for 5, 15 and 60 min with different concentrations of the test substances, in serum-free medium and in medium containing 15% foetal bovine serum (FBS). The cytotoxicity was evaluated by WST-1 test. The EC50 values For HCE, after 15 min exposure and in the presence of FBS, indicate the following order of cytotoxicity: PSE greater than or equal to BAC > CPC > EDTA > PCO. After 1 h exposure the order of decreasing cytotoxicity was PSE greater than or equal to BAC > CPC > PCO > EDTA. In all cases the presence of FBS appeared to exert a protective effect against the cytotoxic effect

Ocular toxicity of some corneal penetration enhancers evaluated by electrophysiology measurements on isolated rabbit corneas

The influence on electrical resistance and membrane potential of rabbit corneas in vitro of some chemicals used as adjuvants in ophthalmic formulations was investigated, in the attempt to correlate changes in electrophysiological properties of the corneal tissue (possibly indicative of toxic/damaging effects to the corneal epithelium), with the promoting effect of the substances on transcorneal permeation in vitro of timolol maleate (TM). The chemicals, tested at different concentrations, were benzalkonium chloride (BAC), sodium ethylenediaminetetraacetate (EDTA), polyoxyethylene-20-stearyl ether (PSE), polyethoxylated castor oil (PCO), deoxycholic acid sodium salt (DC) and cetylpyridinium chloride (CPC). For these substances, definite correlations were found between promoting activity for permeation of TM and modification of electrophysiological parameters. These parameters were in all cases significantly altered by all agents at all concentrations after a 5-h contact. However, after a 1-h contact, 0.001% PSE and CPC did not significantly modify the corneal resistance, while PCO and PSE did not significantly modify the transcorneal potential at the tested concentrations. Only 0.001% PSE, a nonionic surfactant used as solubilizer and emulsifier, active as promoter for TM, did not modify both electrophysiological parameters to a significant extent after 1 h. The results of this study indicate correlations between ocular toxicity, promoting activity for transcorneal permeation of timolol and modification of the electrophysiological parameters. (C) 2003 Elsevier Ltd. All rights reserved

Ophthalmic compositions containing mucoadhesive polysaccharides able to promote corneal re-epithelization

Ophthalmic solutions containing arabinogalactans With a protective activity on the corneal epithelium, particularly suitable for use as arti?cial tears stimulating the recovery of corneal lesions and also particularly useful for contact lens users, containing from 1% to 10% by Weight of arabinoga lactan in an aqueous solution and possible other excipients, among Which tonicity-adjusting agents, pH correctors, buff ers and preservatives, except for benZalkonium chloride. The compositions according to the invention have a virtually negligible viscosity, but are suf?ciently mucoadhesive to assure a considerable permanence time in the area of appli cation. Besides being Well-tolerated, the aforesaid composi tions have considerable re-epitheliZation capacity

Ophthalmic vehicles containing polymer-solubilized tropicamide: "in vitro/in vivo" evaluation

Commercial 1.0% aqueous tropicamide (TR) eyedrops are buffered to sufficiently stable solutions of the weakly basic, poorly soluble drug. These acidic solutions, however, are irritants and may induce copious lachrimation, thus reducing the drug bioavailability. The aim of the present study was to evaluate some solubilizing agents for the preparation of 1.0% TR ophthalmic solutions adjusted at physiologically compatible pH, potentially showing increased eye tolerance, activity, and stability when compared with standard commercial eyedrops. The tested solubilizers were two non-ionic surfactants-Tyloxapol (TY) and Cremophor EL (CR)-and one polymer, Pluronic P85 (PL). Four stable 1% TR formulations, containing 3% TY, 7.5% CR, 15% PL, or 5% CR + 10% PL were submitted to mydriatic activity tests in rabbits. They improved to a small but statistically significant extent the AUC for mydriatic effect of TR in the test animals when compared with commercial 1.0% TR eyedrops