Studies Of Aspirin Transdermal Delivery System

Aspirin (ASA), which has been available for about 100 years, possesses analgesic, anti-inflammatory and antipyretic properties. The platelet aggregation-preventing effect of ASA and its effect in the prevention of cardiac thrombosis were described in the late 60s. ASA influences platelet function and prevents thrombosis by irreversibly inhibiting the thromboxane A₂ synthesis. Thromboxane A₂ is the main cyciooxygenase produce of activated platelets and is proaggregatory and a vasoconstrictor. Therefore, aspirin exerts its antithrombotic action by preventing thromboxane A₂ biosynthesis.Although the use of oral aspirin has been used for these conditions, there are a number of disadvantages associated with this treatment. The compound has been associated with various gastrointestinal side effects, the most severe of which can be gastric bleeding occurring in about 70% of patients taking oral aspirin. Furthermore, the drug is extensivelyhydrolysed by first-pass metabolism and possesses a half-life of about 15 minutes.Therefore, the development of a suitable transdermal delivery system for aspirin would avoid the side effects detailed above and would also prevent first-pass metabolism.The object of this research project was to develop a device for transdermal delivery system of aspirin at a controlled rate over a period of 48h for the effective treatment of platelet aggregation preventing. A series studies including designing of aspirin TDS, studying on pharmaceutical analysis methodology, quality standard studies, evaluation of aspirin TDS efficacy and toxicology of aspirin TDS studies had been conducted.We first confirmed aspirin TDS. The main ingredients, polymer for controlling the permeation rate and permeation enhancers, were chosen thought orthogonal tests. The results showed that S-630 and binary permeation enhancer of IM and PG could make a marked synergistic enhancement of aspirin flux permeation through Guinea pig skin. 10% aspirin was suitable for the system. 20% S-630 and 9% IM-1% PG were confirmed based on the extensive development studies.When adhesive PSA (pressure sensitive adhesive) was 40% in TDS, the patches had good quick stick and shear strength. 1% acetic anhydride could effectively restrain the hydrolysis of aspirin.HPLC method was used to determined aspirin in the patch, its skinpermeation in vitro and plasma concentration of rabbit. This method had high sensitivity, good sensitivity and good accuracy.The modified Franz diffusion ceils were used in the in vitro release and skin permeation experiments. In vitro skin permeation experiment, the excised dorsal guinea pig skin was used as permeation barrier. The result of in vitro release showed that the release curve of aspirin from TDS was accorded with zero-order equation and the release rate was 122.3(o,g-cm"2-h"1. The result of in vitro skin permeation experiment showed that the permeation curve of aspirin from TDS was accorded with zero-order equation. The value of stable permeation rate was 61.9ug-cm"2-h"1.Rabbits were used in the in vivo pharmacokinetic experiment of aspirin TDS. The plasma concentration was analyzed by HPLC.The pharmacokinetic Parameters were calculated by CRFO software. Css.Cnax, AUC0.^, Tmax, t1/2(Ke), \mQQ of aspirin TTS were 84.17 + 23.51ng-mL'1, 84.02+ 23.49ng-mL"1, (4.46+1.37)X lO^g-h-mL'1, 47.88 + 21.23 h, 5.79 + 2.25 h, 1.52+1.02 ho The results above studies indicated that aspirin was capable of 48h continuous delivery of aspirin with a stable permeation rate. Aspirin Transdermal Delivery System was more effective and safer compared with oral aspirin.Quality measures included sample size and shape, homogeneity, detection of relative substances, and release. Ten aspirin TDSs were used...