| Purpose:Skin is the largest organ of human body and the first physical barrier and immune barrier for human body to resist external injury.Skin is easy to be injured.Skin minor trauma and mild infection are common diseases in department of dermatology.In clinic,external preparations are often used for treatment,but there are still some deficiencies in commercial preparations,such as solution,spray,ointment and so on,which have no protective and isolation effect on the wound,easily lost due to friction with clothes,and have no persistent and waterproof effect.The ideal external preparation for the treatment of skin minor trauma and mild infection should have the following characteristics:antibiosis,analgesic,promoting recovery and other effects;can be isolated from the outside world,have a protective effect on the wound;comfortable to use,good permeability;non-toxic,non-allergenic,safe to use;easy to use and carry,suitable for different wounds,including irregular wounds;can release drugs for a long time and reduce the times of administration;can be easily torn off without the painless feeling according to the needs;it is convenient to check the wound healing;it can be waterproof to a certain extent,suitable for more use occasions,and it does not affect the appearance when used.In order to achieve the above objectives,this study plans to prepare a new preparation,namely,diclofenac sodium and chlorhexidine gluconate are selected as model drugs;hydroxypropyl cellulose(HPC),ethyl cellulose(EC)and Eudragit E100 are selected as membrane materials,chitosan hydrochloride as auxiliary membrane materials,triethyl citrate(TEC)as a plasticizer,azone as a transdermal absorption enhancer,ethanol water solution as solvent,a new type of safe,efficient and long-lasting waterproofing film-forming gel has been prepared.Methods:1 Formulation and OptimizationThe dosage of chitosan hydrochloride was determined by single factor test with drug release rate as evaluation index;the optimal dosage of EC,HPC,Eudragit E100 and TEC was determined by orthogonal test L9(3~4)on the basis of single factor test with hydrophobicity,adhesion and drug release rate as evaluation index;different transdermal absorption enhancers were investigated by Franz diffusion cell method.The effects of 2%azone,5%azone and 2%azone+2%borneol on transdermal absorption of Diclofenac sodium(DS)and Chlorhexidine gluconate(CHG)in film-forming gel were determined,and the best penetration enhancer and its dosage were determined.2 Quality controlThe content of DS and CHG in compound diclofenac sodium film-forming gel was determined by High Performance Liquid Chromatography(HPLC)simultaneously.At the same time,the properties,loading capacity,film-forming property,releasability,hydrophobicity and air permeability of the gel were investigated.3 In vitro transdermal characteristicsThe Franz diffusion cell method was used to investigate the percutaneous absorption characteristics of compound diclofenac sodium film-forming gel in intact skin and damaged skin with the cumulative permeation amount and skin retention as indicators.4 Stability studyUsing influence factors,accelerated test and long-term test,the stability of compound diclofenac sodium film-forming gel was evaluated by appearance,film forming,content and release rate.5 Pharmacodynamics StudyThe effect of compound diclofenac sodium film-forming gel on Escherichia coli,Staphylococcus aureus and Pseudomonas aeruginosa was studied by means of perforation and tube continuous dilution method.The analgesic effect of compound diclofenac sodium film-forming gel was investigated in Kunming mice by hot plate method and acetic acid writhing method.A mechanical injury model of mice was established.Objective to investigate the effect of compound diclofenac sodium film-forming gel on wound healing.6 Safety studyTo investigate the irritation of compound diclofenac sodium film-forming gel to guinea pig skin and the acute toxicity to SD rat skin.Results:1 The optimal dosage of chitosan hydrochloride was 2%by single factor test;the optimal dosage of EC,HPC,Eudragit E100 and TEC was 7%,2%,2%and6.5%respectively by orthogonal test;the best enhancer for transdermal absorption was azone,and the best dosage was 2%.2 When the mobile phase was methanol-pH 3.8 potassium dihydrogen phosphate solution(67:33)and the detection wavelength was 260mm,diclofenac sodium and chlorhexidine gluconate could be completely separated with high specificity,precision and recovery.3 The 24h cumulative penetration per unit area and skin retention of diclofenac sodium was appropriate.It could play an analgesic,anti-inflammatory and wound healing role in the local skin and the surrounding tissues.Chlorhexidine gluconate had a low cumulative penetration per unit area and skin retention in 24 hours,which could inhibit local bacteria and control wound infection.4 The influence factors test showed that high temperature and high humidity had certain influence on the stability of the preparation.The accelerated test and long-term test showed that all inspection indexes of the preparation meet the requirements.It was suggested that the compound diclofenac sodium film-forming gel could be sealed in a closed and cool place.5 Pharmacodynamics experiments showed that compound diclofenac sodium film-forming gel had stronger inhibitory effect on Escherichia coli,Staphylococcus aureus and Pseudomonas aeruginosa than the commercial preparations.The high dose group and middle dose group had better analgesic effect and longer duration,and could accelerate wound healing faster.6 Skin irritation and acute toxicity test showed that the compound diclofenac sodium film-forming gel had good safety.Conclusion:The compound diclofenac sodium film-forming gel prepared in this study has the advantages of simple preparation process and controllable quality.It has good analgesic,anti-inflammatory and wound healing effects.It is easy to use and has good air permeability and waterproof function.It has high safety and good stability.The new preparation will have good application prospects. |
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