Effect Of The D-glucosamine Derivatives On The In Vitro Transdermal Delivery Of Diphenhydramine Hydrochloride And Berberine Hydrochloride

Transdermal drug delivery system (TDDS) attracts the attentions from researchers for its advantages. However, the skin barrier limits the percutaneous penetration drugs. Transdermal enhancers were promoted to overcome this barrier. To seek for novel, safe and effective transdermal enhancers, this thesis was focused on the effects of D-glucosamine derivatives on the transdermal delivery of diphenhydramine hydrochloride and berberine hydrochloride.In this dissertation the methods of HPLC and UV were set up separately to determine diphenhydramine and berberine hydrochloride quantitatively. The condition of the transdermal delivery system in vitro was also established. Results indicated that diphenhydramine and berberine were both stable in the phosphatic buffers,the best pH of the donor solution for diphenhydramine was 7.5 while 7.0 for berberine.Meanwhile, effects of D-glucosamine amides on diphenhydramine hydrochloride and berberine hydrochloride transdermal delivery were studied using Azone and Oleic acid as control enhancers. Enhancement effects of D-glucosamine derivatives were studied relating to the chemical structure, including the length of alkyl chain, steric factors, the double bond and polar group. In both series of D-glucosamine amide the compound with 8-carbon atom alkyl group performed the best enhancing effect for diphen- hydramine hydrochloride. However, the compound having 12-carbon atom alkyl group resulted in the best effect for berberine hydrochloride. When the polar group and the length of alkyl chain remain the same, the compound with a double bond in the alkyl chain showed the better permeation enhancement factor. When the alkyl chain was the same, the compound with a glucopyranose as its polar group led to better permeation effect. The steric effect led to a weaker permeation effect for 2-deoxy-2-(4′-alkoxy-3′-methoxycinnamoylamide)-β-D-glucopyranose than 2-deoxy- 2-alkylamide-β-D-glucopyranose. In the end, the enhancement effect of these deriv -atives on diphenhydramine was weaker than on berberine, which suggested they only performed good effect on hydrophilic drugs with smaller molecular weight.In addition, the permeation effect of the new synthesized 1-etheral-D-gluco samine were also studied to diphenhydramine and berberine hydrochloride. the compound with 18-carbon atom alkyl group performed the best enhancing effect for diphen- hydramine hydrochloride while the compound having 12 carbon atoms in the alkyl chain resulted in the best effect for berberine hydrochloride.