| Progesterone is identical to the natural progesterone of the human ovary,which is safe and efficacious,so it is an ideal progestins in hormone replacement therapy. Progesterone can not be administered by oral route. Intramuscular progesterone administration causes pain,irritation and the potential risk of infections,which decreases the compliance. Therefore,alternative means of progesterone delivery,safe and efficacious,have been sought. Transdermal delivery system has become an increasingly popular realm during the last twenty years. The transdermal route of parenteral delivery of drugs provides many advantages over other administration route:maintaining a flatter blood level;avoiding the first-pass metabolism in the intestine and in the liver;ease of use,foster patient compliance;increasing safety when administrationIn this study,the pressure sensitive (PSA) transdermal therapeutic matrix system was considered for administering progesterone and prepared using a general casting method. The transdermal patch is composed by three layers:a drug-free backing layer,a layer of adhesive containing the active ingredients such as drug and skin penetration enhancers,a protective release liner. Polyacrylic adhesive (3M and Ruhm Co.) as PSA matrix matenals may be used in this study. It was found that progesterone and enhancers added in the PSA matrix result in loss of cohesive strength of polyacrylic adhesive,which is evidenced by a large loss of adhesive integrity. The effect of crosslinker and solidifing condition on patch prepared properties was investigated. 1.9 mg cm-2toluene-2,4-diisocyanate crosslinker was added to formulation composed of progesterone 1.0 mg cm-2,ML 2,3 mg cm-2,EP 1.5 mg cm-2,polyacrylate (3M Co.) 3.3 rag-cm-2,and solidifing condition was selected to be 120 3 min,which preparing PSA adhesives maintain white,integrity and still good tack. The same content succimc acid crosslinker added to formulation composed of progesterone 1.0 mg-cm-2,ML 2.3 rag-cm-2,EP 1.5 rag-cm-2,Eudragit E 100(Ruhm Co.) 3.3 mg cm-2,and solidifing condition was selected to be 60 10 min,which preparing PSA adhesives also maintain integrity.In an effort to enhance the permeation rate of progesterone,three methods including the use of skin penetration enhancers,the increase of the drug load of the system,the use of various polyacrylic adhesive have been studied. The in vitro skin permeation tests from each patch through human skin were carried out by Valia-Chien diffusion cell consisting of two compartment and high performance liquid chromatography (HPLC) method. The results showed that the permeation rate of progesterone was dramatically enhanced by ML;lag time was not dramatically extended. In the PSA patches containing ML from 17% w/w to 25% w/w,permeation increased with increase of ML concentration up to 23% w/w,but little change in permeation was found with more than 23% w/w. Compared to lag time in 0% w/w ML patch,increasing ML concentration (17-21% w/w) didri t result in an extend of lag time;ML concentration 23% w/w in PSA matrix only extend 1.2 h. It was found the combination of ML and EP produces a rather large increase in permeation rate of progesterone. PSA matrix consisting of 23% w/w ML and 15% w/w EP showed the optimal permeation,mean permeation rate 1.50+0.64 /g cm-2 h"1,with a 21 fold enhancement,but lag time was extended 2.3 h. Progesterone concentration in the PSA has also found to have an effect on the permeation. The skin permeation rate wasincreased from 0.20+0.05ug cm-2 h-1 to 0.64+0.11ug cm-2 h-1 as progesterone concentration from 7.5 % w/w to 10.0% w/w and did not change as the increase of concentration from 10.0% w/w to 12.5% w/w. But lag time was unaffected by concentration between 7.5% w/w,10.0% w/w,12.5% w/w. Polyacrylic adhesives from 3M and Ruhm Co. used as PSA materials,were found to provide similar skin permeation and lag time of progesterone across human skin.The in vitro release tests from each patch were evaluated using Valia-Chien diffusion cell and HPLC method. It was f... |
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