ABSTRACT
This study focused on the in vitro evaluation of skin perforation using a new microneedle device (Dermaroller) with different needle lengths (150, 500 and 1500 microm). The influence of the microneedle treatment on the morphology of the skin surface (studied by light and scanning electron microscopy), on the transepidermal water loss (TEWL) and on the penetration and permeation of hydrophilic model drugs was investigated using excised human full-thickness skin. Furthermore, invasomes - highly flexible phospholipid vesicles containing terpenes and ethanol as penetration enhancer - were compared with an aqueous solution. Elevated TEWL values were measured after Dermaroller treatment compared to untreated human skin with a gradual increase of the TEWL over the first hour whereas afterwards the TEWL values decreased probably caused by a reduction of the pore size with time. Skin perforation with the Dermarollers enhanced drug penetration and permeation for both formulations tested. Invasomes were more effective to deliver hydrophilic compounds into and through the skin compared to the aqueous drug solutions and the combination with skin perforation further enhanced drug penetration and permeation. In conclusion, Dermarollers being already commercially available for cosmetic purposes appear also promising for drug delivery purposes particularly those with medium (500 microm) and shorter (150 microm) needle lengths.
Subject(s)
Administration, Cutaneous , Needles , Skin/metabolism , Humans , Microscopy, Electron, Scanning , Particle Size , Water/metabolismABSTRACT
The condensation of 5-nitrosalicoylchloride and 5-sulphamoylsalicylic acid with certain amines is described. Reacting the acid chloride with 3-amino-2-oxazolidone, 4-aminophenazone, thiosemicarbazide, 1-aminohydantoin and 2-aminopyridine yielded the correspondong N-substituted 5-nitrosalicylamides (1a-c), while with semicarbazide a disubstituted product type 2 was obtained. On the other hand, when 5-sulphamoylsalicylic acid was condensed with o-chloroaniline, m-chloroaniline and 4-aminophenazone in the presence of phosphorus trichloride, instead of affording the expected condensation products type 3, it yielded N1N5-disubstituted 5-sulphamoylsalicylamides (4a-c). The synthesized compounds were screened for antimicrobial activity.
Subject(s)
Antifungal Agents/chemical synthesis , Salicylamides/chemical synthesis , Bacteria/drug effects , Chemical Phenomena , Chemistry , Indicators and Reagents , Microbial Sensitivity Tests , Salicylamides/pharmacologyABSTRACT
The condensation of 3.4.5-trimethoxybenzyl chloride with certain amines is described. Reacting the aralkyl chloride with 4-aminophenazone, 2-aminopyridine, piperidine, N-methylpiperazine, pyrrolidine and morpholine yielded the corresponding trimethoxybenzyl derivatives la--f. On the other hand, alpha-[3.4.5-trimethoxybenzamido]-glutarimide (2) was synthesized via the acylation of glutamic acid with trimethoxybenzoyl chloride, dehydration of the N-acyl derivative and finally imidation of the inner anhydride thus formed.
Subject(s)
Anisoles/chemical synthesis , Aminopyrine , Central Nervous System/drug effects , Morpholines , Piperazines , Piperidines , PyrrolidinesABSTRACT
The condensation of 4-chloroanthranilic acid with several substituted monophenylureas is described. Reacting equimolecular amounts of the haloanthranilic acid with monophenylurea, p-tolylurea, p-methoxyphenylurea, p-ethoxyphenylurea, p-bromophenylurea, p-chlorophenylurea and m-chlorophenylurea--by fusion in a pressure bottle--yielded the corresponding 7-chloro-3-aryl-.2.3.4-tetrahydro-2.4-dioxoquinazoline (1a--g). On the other hand, o-substitute phenylureas, instead of affording the expected condensation products, yielded a compound which was shown to be 7-chlorobenzoyleneurea (2), the formation of which is accounted for.
