The Preparation Of Pulsatilla Radix Spray Film Agent

Arthritis is a chronic systemic disease with complicated pathogenesis.Various traditional Chinese medicine dosage forms have been widely used to treat arthritis,however,considering the disadvantages of traditional praparations,such as inconvenient modulation,contaminated clothing,sticky skin,poor breathability,small drug loading,unregulated dose and so on,novel alternative dosageforms need to be introduced.The spray film agent is a new preparation,which has the advantages of both spray agent and membrane agent.It is a solution and sprays out in the form of a fog to forms a film that adheres to the surface of the skin after the solvent is dried.It inherits many advantages,such as does not affect normal activity,does not pollute clothing,and is convenient to use,and suitable for joints and other more active skin surface especially.In this paper,a spray film agent was developed with Pulsatillae Radix,treat rheumatoid arthritis and osteoarthritis in folk,as the main drug.The specific contents of the study are as follows:1.Pre-prescription study on the extract of Pulsatillae Radix.The solubility of the extract of Pulsatillae Radix was studied by precipitation method,index component method and particle size determination method.The equilibrium solubility and oil-water partition coefficient of the extract of Pulsatillae Radix were also determined.The results show that the extract of Pulsatillae Radix has the best dissolving ability in water,and it is more soluble in alkaline solution than in acidic solution.The solubility decreases gradually with the increase of alcohol concentration.But it is poor in ethanol,methanol,propylene glycol and glycerol.The extract of Pulsatillae Radix has strong hydrophilicity and its logP is less than 0 in alkaline environment and has strong lipophilicity in acid environment.2.Preparation of Pulsatillae Radix spray film agent.The film-forming materials were screened according to the spray effect and film-forming condition.The effects of the dosage of film forming materials and corresponding auxiliary materials on the spray area,film forming time,membrane performance and solution state were investigated by single factor test.According to the comprehensive score of the spray film agent,the optimum formulation was determined by centeal composite design-response surface method: PVA-0588 was 4.54 g,P407 was 0.96 g,glycerol was 3.0 ml,and the optimum dosage of borneol is 2.5%.3.Study on the quality evaluation and transdermal absorption of Pulsatillae Radix spray film.The quality evaluation of the prepared spray agent of Pulsatillae Radix was carried out,including traits,identification,examination,characterization and content determination.The release characteristics of the spray film were studied by transdermal absorption test.The results showed that the quality evaluation of Pulsatillae Radix spray film was good.The cumulative release of both drugs is in accordance with the higuchi kinetic equation,which shows that the spray film itself has the characteristics of sustained release.The addition of the enhancer can promote the transdermal absorption of the drug,but it will not change the drug release characteristics.4.Pharmacodynamic evaluation and skin acute toxicity and irritation of Pulsatillae Radix spray film agent.The pharmacodynamics of Pulsatillae Radix spray film was studied by foot swelling test in adjuvant arthritis model rats and analgesic experiment in mice.The results showed that the spray could reduce the swelling degree and arthritis index of foot.It could also reduce the content of TNF-?,IL-1?,IL-6 and CRP in serum of rats.The hot plate analgesia test and acetic acid writhing test showed that which indicated that Pulsatillae Radix spray film had analgesic effect.Safety evaluation of acute toxicity test and skin irritation test were studied in rats.The results showed that there was no acute toxic reaction and no irritant reaction to the skin of rats.5.The study on the stability of Pulsatillae Radix spray film agent.According to the principle of stability test in the fourth part of Chinese Pharmacopoeia(2015 edition),the stability of Pulsatillae Radix spray film was evaluated by examining the stability of open group,transparent bottle group and light-avoiding bottle group,including high temperature test,high humidity test and intense light irradiation test.The results showed that the spray agent was kept in a light-proof spray bottle,and the stability of the preparation was good.This paper has successfully developed Pulsatillae Radix spray film agent,which has the advantages of good quality and stability,good pharmacodynamics,safe and non-irritating,and is a potential new preparation form.