| Hyaluronic acid is a kind of natural sticky polysaccharide,which is widely distributed in the tissues and organs of organisms,and plays a very important role in the life activities.Sodium hyaluronate is a sodium salt of hyaluronic acid,which is the main application form of hyaluronic acid.In this paper,sodium hyaluronate was prepared into binary ethosomes,which increased the transdermal effect and stability of the drug.And then the binary ethosomes were prepared into cataplasm.A new transdermal drug delivery system of sodium hyaluronate was designed.The following work is performed:1.An analytical method of sodium hyaluronate in vitro was established.The linear range,stability,recovery,intra-day and inter-day precision of sodium hyaluronate were investigated by UV-visible spectrophotometry.The results showed that the concentration of glucuronic acid in the range from 10μg/m L to 70μg/m L showed a good linear relationship with the absorbance.The linear regression equation is A=0.01463*C+0.0175,R~2=0.9991.The recovery rate was in the range of 90%～101%,and the intra-day and inter-day precision RSDs were less than 2%.2.The formula of sodium hyaluronate binary ethosomes was investigated.The particle size,Zeta potential and encapsulation efficiency were used as indicators.The concentration range of ethanol,binary alcohol phase,soybean lecithin,cholesterol,sodium hyaluronate and p H value of PBS were determined by single factor experiments.The optimal conditions for optimization by orthogonal test design were:ethanol 10 m L,cholesterol 20 mg,p H value of PBS 6.4,sodium hyaluronate 20 mg.The results showed that the average particle size of sodium hyaluronate binary ethosomes was 194.89 nm,the average Zeta potential was-23.97 m V,and the average encapsulation efficiency was86.18%.Stability experiment showed that the particle size and encapsulation efficiency of the sodium hyaluronate binary ethosomes are stable at 4℃,and the binary ethosomes should be sealed and stored at low temperature.3.Different transdermal drug delivery systems of Sodium hyaluronate were compared.Sodium hyaluronate was prepared into liposomes,ethosomes and binary ethosomes respectively.The particle size,Zeta potential and encapsulation efficiency of three kinds of transdermal drug delivery systems were measured and compared.The results showed that the comprehensive properties of sodium hyaluronate binary ethosomes were better than those of liposomes and ethosomes.Through in vitro percutaneous infiltration experiments,it was found that the cumulative infiltration amount of the three transdermal drug delivery systems in 8 h was binary ethosomes>ethosomes>liposomes in descending order.The experimental results showed that the cumulative infiltration amount of the sodium hyaluronate binary ethosomes in 8 h was the largest and the percutaneous infiltration behavior met the zero-order equation.4.The prescription of sodium hyaluronate cataplasm was investigated.NP-700was selected as the frame material,aluminum glycol as the cross-linking agent,DL-tartaric acid as the adjustor,sodium carboxymethyl cellulose as the viscosity increaser,diatomite as the filler,glycerol as the humectant.Based on the single factor test,the initial adhesion,holding adhesion and sensory evaluation were used as comprehensive indexes.The orthogonal test design method was used to optimize the dosage of NP-700,aluminum glycol,DL-tartaric acid and glycerol.The order of influence of various factors on the comprehensive evaluation of the cataplasm was as follows:NP-700>glycerol>aluminum glycol>DL-tartaric acid.Therefore,the optimal formula for cataplasm is NP-700 5.54%,aluminum glycol 1.62%,DL-tartaric acid 6.47%,glycerol 36.95%.Through in vitro percutaneous infiltration experiments,the dosage of sodium hyaluronate binary ethosomes was determined to be 60 m L(Based on total paste weight was 200g).5.The preparation process of sodium hyaluronate cataplasm was investigated.Through experiments,NP-700,sodium carboxymethyl cellulose and diatomite was added to oil phase,DL-tartaric acid and hydroxyl aluminum glycol was added to water phase.The preparation process of water phase and matrix forming process were investigated.The results were as follows:the mixing temperature of water phase was40℃,the mixing time of water phase was 20 min,the mixing temperature of matrix was 30℃,the mixing time of matrix was 10 min,and the drying time was 1 d.The initial adhesion of sodium hyaluronate cataplasm was increased from No.11 ball to No.15 ball.It shows that the optimized preparation process can improve the quality of sodium hyaluronate cataplasm. |
