Study On Diclofenac Sodium Hydrogel Prepared By Irradiation As Transdermal Drug Delivery System

With the irradiation cross-linking technology, high molecule materials were irradiated by ⁶⁰Co to make the hydrogel, a transdermal delivery system. Then, the properties, preparation technology, permeability and stability of the irradiation-formed hydrogel were studied with diclofenac sodium as candidate drug. Moreover, the Lvabrasol, a kind of surfactant was also used to improve the drug loading and stability of diclofenac sodium hydrogel. The prescription of the high molecule materials were optimized with orthogonal design. Artificial skin was used to evaluate the permeability of diclofenac sodium hydrogel and others diclofenac sodium preparations. The data indicated that the radiation cross-linking formed hydrogel with high molecule materials had the reticular structure, and showing great benefit for the permeability of the drug through the skin.This study included the following four parts:1. Study on the preparation technique of diclofenac sodium hydrogel1.1 Study on the preparation and properties of irradiation cross-linking formed hydrogelSwelling rate, gel fraction and tensile bond strength of the blank hydrogel with three different prescriptions were determined. The results showed that swelling rate could increase with the reduction of gel fraction. Moreover, tensile bond strength was found to be the critical factor for shapping of the hydrogel. The hydrogel could not well keep the shape when the tensile bond strength was too low, and not suit for the transdermal delivery system due to the fragility increase when the tensile bond strength was too high. Because the PVA was the most important factor in increasing the tensile bond strength, the same we testify the content of PVA should not less than 8% in the hydrogel.1.2 Study on the drug loading in diclofenac sodium hydrogelDue to the high solubility of diclofenac sodium in ethanol and low in water, the ethanol was primarily used to dissolve the drug in order to increase the drug loading of diclofenac sodium in hydrogel. However, it was found that the ethanol could affect the cross-linking of high molecular materials exposed to the irradiation ambience, so the water was the only choice as the solvent of diclofenac sodium hydrogel.It showed that the hydrogel could form with regular shape, well distributed and high transparency when the content of diclofenac sodium in hydrogel was 0.25%. But, when the content of the drug was above 0.28%, the crystal will be precipitated from the hydrogel. Therefore, the highest drug loading in diclofenac sodium hydrogel is not more than 0.25%.Addition of the surfactant to the solvent was a good way to increase the drug loading of diclofenac sodium in hydrogel. Three kinds of surfactants, Labrasol, Cremophor EL and Tween-80, respectively, were used to exhibit their impact on the hydrogel. As a result, no significant difference was observed among them in keeping the shape of the hydrogel, but Labrasol can enhance the drug loading of diclofenac sodium in hydrogel.1.3 Study on the preparation technique of diclofenac sodium hydrogelIn the orthogonal design, the tensile bond strength, crystal precipitation and the quantity of the gas bubble formed were determined as the evaluation standards to screen the prescription of diclofenac sodium hydrogel. The results showed the best prescription of hydrogel should be 8% PVA, 0.5% diclofenac sodium and 0.15% Labrasol.2. Study on the impact of Labrasol on the permeability and stability of diclofenac sodium hydrogel2.1 Development of HPLC method to assay the content of diclofenac sodium in the hydrogelCia column was used as the stationary phase. The mobile phase was the solution containing acetonitrile:0.25% H4PO3 (60:40), pH=3.0. Other conditions included Flow rate 0.8 ml/min, the wavelength of UV detection 276 nm, sample 10 jj.1 and temperature of column 26 °C. The results indicated that this method was simple, rapid, accurate and suitable to assay the content of the drug.2.2 Study on the impact of Labrasol on the permeability of diclofenac sodiumhydrogelWith optimized Franz diffuse well, artificial skin and 10% ethanol as the acceptor solution, 0, 0.5%, 1.5%, 3% and 4.5% Larbrasol were respectively added into the 0.25% diclofenac sodium hydrogel to evaluate the effect of Labrasol on the permeability of drug in hydrogel. The results suggested that the kp, a parameter to evaluate the permeable ability of the drug through the skin, decreased with the increase of Labrasol, which indicated that Labrasol could delay the permeability of diclofenac sodium in the hydrogel through the skin.2.3 Study on the impact of Labrasol on the stability of diclofenac sodium hydrogelWith optimized Franz diffuse well, artificial skin and 10% ethanol as the acceptor solution, 0% and 1.5% Larbrasol were respectively added into the 0.25% diclofenac sodium hydrogel to evaluate the effection of Labrasol on the stability of drug in hydrogel. The results suggested that the Labrasol could improve the stability of diclofenac sodium in the hydrogel not only during the irradiation but also in the long period.3. Study on the comparison of the permeability between radiation formed diclofenac sodium hydrogel and others diclofenac sodium pharmaceutics3.1 Study on the comparison of the permeability between irradiation formed diclofenac sodium hydrogel and pre-irradiation solution of high molecular materials with diclofenac sodiumWith optimized Franz diffuse well, artificial skin and 10% ethanol as the acceptor solution, comparison of the permeability between irradiation formed diclofenac sodium hydrogel and pre-irradiation solution of high molecular materials with diclofenac sodium was performanced. (kpx105) of them were 71.09±6.30 and 13.99±0.51, respectively, and the former was 5.08 times than the latter. Results indicated that the irradiation of high molecular materials could form the hydrogel with regular reticular formation so as to greatly increase the skin permeability of the drug.3.2 Study on the comparison of the permeability between irradiation formed diclofenac sodium hydrogel and diclofenac sodium carbomer gelWith optimized Franz diffuse well, artificial skin and 10% ethanol as the acceptor solution, the permeability among the radiation formed diclofenac sodiumhydrogel and diclofenac sodium carbomer gel without Labrasol and with 0.15% Labrasol was compared. The kp of three were 71.31±8.12, 57.27±2.60 %i 38.57±3.80 respectively, and kp of the former was 1.25 times and 1.85 times than that of the other two. Those data showed that the radiation formed hydrogel of diclofenac sodium is suitable to be the transdermal delivery system.4. Study on the federal hazardous substances act of diclofenac sodium hydrogelAt last, federal hazardous substances act were perfomed to identify the stimulation of diclofenac sodium hydrogel. As a result, no stimulation was seen for normal or damaged skin.Our work verified that the radiation formed hydrogel of diclofenac sodium is suitable to be the transdermal delivery system, and with the further work the diclofenac sodium hydrogel could be used as a new clinical medicine. Moreover, more hydrogel of Chinese traditional medicine could be prepared to improve the progress of the aggiornamento of Chinese traditional medicine.