Delay Colonic Ph-sensitive Targeting Agents

Objective:To develop a new colon-specific preparation using the Traditional Chinese Medicine Compound which is composed of Berberine and Radix Aucklandiae Ex.Mixing the Berberine,Radix Aucklandiae Ex with eligible adjuvants, so as to prepare tablets core with high dissolution speed by wet granulation and tabletting.The colon-specific tablets were prepared in a coating pan using Eudragit L100 and Eudragit S100 as the outer pH-sensitive layer and Surelease as the time-lag layer.Preliminary feasibility discussion of this TCM composite formula were conducted through in vitro release,in vivo biological release,and the foundation for further TCM OCDDS formula redesign were laid.Methods:(1)Study on preparation technology:optimum accessories and preparation technology of tablets core were determined by monofactorial study,the production procedure for coating and coating materials of colon-targeted tablets were selected through coating pan,the best procedures for two kinds of coating material Eudragit and Surelease were also determined through in vitro release.(2)Release behaviors test in vitro:To study the effects of pH,retention time in stomach,rate of rotation and release medium to the release behaviors of coated tablets.(3)In vivo test of rats:The 3mm diameter colon-specific tablets which to be used specially for rats were prepared,the berberine content in each gastrointestinal segments were determined after an oral administration to prove the tablets whether or not meeting the release requirement of colon-specific tablets.(4)Quality specification of the tablets: The quality specification of the tablets' appear ance,qualitation identification and assaying were made.(5)Study the release mechanism:The release mechanism of coated tablets were researched through the hydrating swelling experiment.Results:Through procedure selection,the best processing method was determined as follows:Mixing the Radix Aucklandiae Ex and Berberine with MCC, CMS-Na,the granula was prepared by wet granulation method with 70%ethanol,add 0.5%(W/W)magnesium stearate as lubricant after the granula was dried,then the tablet core with degree of hardness 4kgs was made.In vitro release experiments shown that the drug release exceed 90%in 10 minutes,so tablet core can not block the drug release.From interior to exterior the tablet core was coated with time-lag layer and pH-sensitive layer respectively.When the pH-sensitive layer increased 4%and the time-lag layer increased 6%,the release beginning time of drug could be controlled at 3h after the tablets reaching small intestine without the effecting of gastric emptying,meeting the release requirement of colon-specific tablets.(2)In vivo test of rats:the colon-specific tablets can pass safely through stomach,small intestinal anterior and middle parts,berberine released mostly in small intestinal terminatio, ileocecal junction and colon,basically meeting the in vivo release requirement of colon-specific tablets.Conclusion:On the base of tablet core,the desired results of colon-specific delivery can be reached using time-lag layer and enteric layer by changing their coating level.The colon-specific characteristics of berberine colon-specific coated tablets were obvious both in vivo and in vitro.The intestinal tract region where tablets located can only decide the drug release.