Research On PH-Sensitive In Situ Gel For The Topical Treatment Of Colitis

Ulcerative colitis(UC)is a chronic non-specific inflammatory disease that primarily affects the colonic mucosa.mesalamine(5-amino salicylic acid(5-ASA))remains as a first line drug for treating mild to moderate UC because of definite efficiency and less side effects.Rectally administered mesala-mine formulations,which include suppositories and enemas,offer the advantage of delivering a known amount of mesalamine topically to the distal colon,however both of them are imperfect in clinical use.Suppositories can only acts on rectum,its action time and contact area with lesions are limited.Though enemas can reach the sigmoid colon,they stays just only for a while because of the influence of peristalsis.In order to prolong contacting time of the drug,enhance the therapeutic effect,reduce the frequency of drug delivery and improve patient compliance,our subject has 5-ASA pH sensitive gel enema was developed in this paper.This enema can keep liquid state before use so that the drug can be administrated more conveniently.And it can gelated at pH6.8?7.8 so that the drug stays longer at diseased region compared with ordinary enema.5-ASA pH sensitive gel enema was prepared with Carbomer as gel matrix and the xanthan gum as thickener.Through signal-factor experiment,Effects of mixing time,pH of gel and the concentrations of Carbomer?xanthan gum and anti oxygen on the characteristics of pH sensitive gel were investigated.Orthogonal design,factor design and response surface methodology were used to optimize the amount of Carbomer,xanthan gum and anti oxygen.The quality parameters of three batch pH sensitive gel prepared with the optimal formulation and technology was as follows:pH 4.0?5.0;gelling viscosity before:500?1000(mPa-s);gelling viscosity after:2200?2700(mPa·s);inversing time:40?80(min);volume ratio of sedimentation:98.5%?100%.5-ASA can decarboxylate to benzoquinone and hydroquinone,or gentisic acid under the light and heat.At higher temperatures,it can also decarboxylate to aminophenol.Both gentisic acid and aminophenol are useless and toxicity.Gradient elution chromatography was applied to measure and analyze 5-ASA and those related substances in this research.Specific chromatographic mobile phase system were PBS(pH7.5)-TBAH-methanol-water(600:50:50:300)and PBS(pH7.5)-TBAH-methanol-water(200:50:300:450).In this chromatographic conditions,5-ASA and its degradation products can be separated completely.RSD of repeatability was 1.177%.In the concentration range of 25?250?g· ML-1,the linear regression equation wasA = 2.3 ×106C +6.85 × 107(r = 0.9997),concentration and peak area had a good linear relationship.The average recovery rate was 99.44%(n = 9),RSD was 0.94%(n = 9).The influencing factor tests(60?,RH75%,45001x)and acceleration tests(40 ?,RH75%)were performed with appearance,pH,drug content and related substances as ananlysis items.It was shown in the acceleration tests that the results of ananlysis items of 5-ASA pH sensitive gel enema had not significantly changed.