Preparation Of Zaltoprofen Gel And Study Of Drug Release In Vitro

Osteoarthritis is a serious hazard to human health of diseases.It is characterized by high incidence,high disability efficiency,and complex pathogenesis,making the disease of prevention and treatment become difficult.Thus this kind of drug therapy has been a focus of pharmacy workers.Zaltoprofen,is developed by Chemiphar Company-a Japanese enterprise in 1993 for the first time,which is listed a new class of non-propionate steroidal anti-inflammatory,analgesic, antipyretic drugs,for the treatment of chronic rheumatic Arthritis,deformation of arthritis, low back pain disease,inflammation around the shoulder,neck and carpal tunnel syndrome after surgery,and post-traumatic tooth extraction after the anti-inflammatory analgesic.It is not in market in China today.Zaltoprofen has commodities selectivity in the inflammation site,and its anti-inflammatory effect is significantly higher than that of similar drugs such as indomethacin,diclofenac,naproxen,ibuprofen.It has the characteristics of high efficiency and low gastric side effects.However similar to other non-steroidal anti-inflammatory analgesic drugs,it is possible to cause some major adverse reaction such as stomach discomfort,stomach pain,gas,diarrhea and other gastrointestinal symptoms,and a rash,skin rash and other allergic symptoms,also headache,lethargy,and other nervous system adverse reactions if administering Zaltoprofen orally.Even in serious patients,acute renal failure,liver dysfunction,peptic ulcer disease might happen.So preparing Zaltoprofen percutaneous forms is not only conducive to arthritis,pain and inflammation treatment,but also to overcome caused by the oral side effects.And it will certainly play a better role in treatment.This paper first established a method for the determination of Zaltoprofen;the physical and chemical properties of Zaltoprofen were measured;studied Zaltoprofen gel permeability using improved Franz diffusion cell with abdominal skin of mice in vitro,and investigated the impact on percutaneous penetration by the pH of the gel,Carbomer concentration,and penetration enhancer.Based on single factor test,the optimum prescription is optimized by the index of accumulated amount using orthogonal design with three factors such as Carbomer concentration,Azone,propylene glycol and three levels;its in vitro release and permeation mechanism were studied also;the preliminary stability of ZTPF was studied by stability test,including determination of pH,heat experiments,cold experiment, centrifugal experiments,staying at room temperature and accelerated experiments;the acute toxicity of the skin,skin allergies and irritation test pilot were studied to observe animal skin action after contact with Zaltoprofen gel in short time and and the immune system toxicity after repeated provocative responseThe experimental results showed that UV spectrophotometry standard curve,precision and the recovery of ZTPF were fit to the requirement of determination,the adjuncts had non-interference in determination,the UV method was simple,fast and high accuracy; Carbomer concentration of propylene glycol,Azone had greater influence on permeability of ZTPF gel in vitro;the best prescription optimized with orthogonal design contained 0.75%Carbomer,1.0%Azone;15%propylene glycol;ZTPRF gel percutaneous permeation process accorded with Higuchi equation(r=0.997),in vitro release process with zero-order kinetics equation(r=0.999),in line with the general law of fat-soluble drugs;ZTPF gel performed good stability at room temperature stability,but under the condition of high temperature its color deepened,so it was proposed that the storage conditions should avoid high-temperature;Zatop-rofen gel was proved non-toxic and irritating through the acute toxicity tests,skin irritation and allergic test pilot.Zatoprofen gel could increase the local concentration,with a high degree of security and good convenience,besides a reduced dosage also could get the same treatment efficiency, reduce the gastrointestinal tract and the body of the organizations.Organ toxicity.Thus Zatoprofen gel is a safe medicine preparation of skin surface.