Preparation And In Vitro Evaluation Of Releasing Properties Of Fibrauretinum Colon-specific Delivery Coated Tablets

Objective：A kind of alkaloid, Fibrauretinum, obtained from MenispermaceaeFibaurea recisa Pierre, is widely used for removing heat and detoxification. Especially,for its obvious antiviral and broad-spectrum antibacterial actions, Fibrauretinum is notedfor pure natural herbal antibiotics. In the paper, Fibrauretinum was chosen as the modeldrug, and combined with oral colon-specific drug delivery system. According to the drugrelease principle, the pH dependent and time delay, it prepared Fibrauretinumcolon-specific delivery coated tablets. The coated tablets improved the drugconcentration in the therapeutic area, upgraded the local bioavailability, reducedsystemic side effects, and being good for patients’ compliance. All these features wouldshow a improving to the bioavailability and will become the basis of innovation inTraditional medicine finally.Methods：①study on preformulation Investigation of Fibrauretinum on physicaland chemical properties, powder property, compatibility between drugs and excipients,initial stability. And according to this basis, establish the release testing methods invitro and prepare for the follow-up study.②S tudy on preparation formulaandproduction process Taking tablets appearance characteristics, time of disintegrationor dissolution as an evaluation index, the composition and the optimum processcondition of the core tablets were chosen by single factor experiments. The preparationparameters of coating were investigated by evaluation of the film coating uniformity.The multi-layered coating is designed by isolation layer, time-lag layer and enteric layer in turn. Through extensive tests, the prescription composition and type ofplasticizer were filtered. Release of drugs in artificial gastric fluids being an evaluationindex, each layer of coating composition and coating weight were investigated byorthogonal design test.③S tudy on the quality standards Detectminingpalmatinehydrochloride in Fibrauretinum colon-specific delivery coated tablets by HPLC. Andthe inspection items such as the appearance, properties, qualitative, differences inweight, and in vitro dissolution, etc, were included in the tablet quality standards.④I nvestigation on the initial stability Using the means of accelerated testing andlong-term stability testing to examine the stability of preparation.Results：①Study on preformulation Palmatine powder with poor fluidity andmoisture absorbability, is sensitive to moisture and heat. It has a good compatibilitywith accessories and meets slot leakage condition for the selected media.②Study onpreparation formula and production process The composition of core tablets was asfollows: Fibrauretinum100mg per film, MCC135mg per film, glucose16.2mg perfilm, CMS-Na16.2mg per film,4%HPMC water solution just the right amount,Magnesium sterate2.2mg per film. The coating preparation was as follows: theisolation layer was HPMC3g, PEG60000.3g and70%ethanol100mL; time-lag layerwas Polyacrylic Resin Ⅳ5g,PVP K302g, PEG60001g and80%ethanol100mL;enteric layer was Polyacrylic Resin Ⅱ0.6g, Polyacrylic Resin Ⅲ2.4g,Castor oil0.9g,DEP1.2g and95%ethanol100mL. The coating weight gains of four layers are2.0%,7.0%and6.0%. The coated tablets have no drug release in pH1.0artificial gastric fluidin2h. In pH6.8artificial small intestine fluid, dissolution rate was less than1%for3.5h．In pH7.6artificial colonic fluid, the coated tablets showed sustained-releasebehavior, drug was completely released within8h.③Study on the quality standardsEstablish the method to detectmine the palmatine hydrochloride in Fibrauretinecolon-specific delivery coated tablets with HPLC. And study out the draftquality standard for the coated tablets.④Investigation on the initial stability Theaccelerate test and long-term stability test show that the tablets did not changesignificantly compared with0month.Conclusions: The optimal prescription and preparation of Fibrauretine colon-specific delivery coated tablets have been filtered out. And it shows rational,stable and simple. The indexes of the tablets meet the purposed requirements. The draftquality standard of coated tablets is created. It’s proved sensitive, accurate, reproducibleand specific. The preliminary stability tests show the quality of Fibrauretinecolon-specific delivery coated tablets is stable. And the period of validity of the coatedtablets is1year.