| Oral ulcer is very common clinical disease of the oral mucosa,and it is very easy to break out repeatedly,and the ulcer surface will have a burning sensation and pain.Amlexanox is the only drug used in the treatment of oral ulcer with FDA approved,promote ulcer healing and prevent the recurrence.But the analgesic effect of the drug is not satisfactory Ropivacaine hydrochloride has the advantages of high hydrophilicity and low fat solubility,and its intrinsic vasoconstriction function makes it easy to stay in the local.The traditional oral bioadhesive tablets in order to extend the residence time of drugs in the oral cavity,need to join the biological adhesive materials to a certain extent hindered drug fast work.Based on the above reasons,this paper will combine amlexanox and ropivacaine hydrochloride,and through the novel fast / slow release tablet type double layer design to give full play to their respective characteristics of drugs,better play fast pain relief and promote healing therapy.Local anesthetics ropivacaine hydrochloride locates in quick release layer,which can play the role of rapid onset;amlexanox locates in the adhesion layer,which can last adhesion to the ulcer surface,protect the lesions and slow release of drugs after quick release layer disintegrating.This topic research content mainly includes:ropivacaine hydrochloride quick release formulation optimization;adhesive layer formulation optimization layer;preparation and quality evaluation on ropivacaine hydrochloride/ amlexanox buccal rapid sustained-release adhesive tablets;in vivo release profile of double tablets.Firstly,in the optimization of the formulation of the rapid release layer of ropivacaine hydrochloride,the types and dosage of the filler and the disintegrating agent were screened with the taste,disintegration time and dissolution as the index.The optimized prescription of ropivacaine hydrochloride 2mg,L-HPC 1.65mg(5%),MCC 14.67 mg,mannitol 14.67 mg,aspartame 0.5mg,magnesium stearate 0.5mg,and disintegration time was about 19.4s,the in vitro release test showed that when the in vitro release percentage of ropivacaine hydrochloride rapid release tablets at 5min was more than 95%.Single factor study on adhesion of bioadhesive materials showed that the ratio of CP974 p to HPMCK4 M was related to the adhesive force,swelling rate and adhesion time,There is a certain relationship between the swelling rate and the adhesion force,when the ratio of CP974 p to HPMC K4 M was 1:2 to 2:1,the adhesion force and the swelling rate of blank buccal adhesive tablets is larger and adhesion suitable time is long.Direct power compressed method was used to prepare of amlexanox sustained release adhensive layer.The ratio of HPMC K4 M to CP974 p was optimized by the adhesion force,the swelling rate and adhesion time.In this paper,direct powder compressed and twice compressed method were used to prepare rapid released/ sustained-released buccal adhesive tablets.The adhesion force of the tablet,disintegration time and in vitro release rate was applied as index to optimize prescription.The results showed that the optimal formulation of tablets had good adhesion,short disintegration time,appropriate release proflie,and good taste.This paper also established the quality control method of double buccal adhesive tablets.The results of the stability tests provided a reference for the later packaging and storage.The study of double buccal adhesive tablets on healthy volunteers showed that the ropivacaine hydrochloride fast release layer can rapid onset,amlexanox adhesion layer can maintain drug concentration for a long time in the oral cavity.It did not cause irritation or pain and has a good comfort and compliance. |
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