Design, development and in vitro-in vivo study of a colon-specific fast disintegrating tablet.
OBJECTIVE
Targeted delivery systems for the treatment of Inflammatory bowel disease (IBD) are designed to increase local tissue concentrations of anti-inflammatory drugs from lower doses compared with systemic administration. The objective of this study was to formulate and evaluate an oral system designed to achieve site-specific and instant drug release in the colon for effective treatment of IBD.


METHODS
The system consists of a core tablet containing the model drug diclofenac sodium, superdisintegrant sodium starch glycolate, and coated with enteric polymer Eudragit FS 30 D to achieve different total percentage weight gain. Drug release studies were carried out using a changing pH method. A placebo formulation containing barium sulphate in the tablet was administered to human volunteers for in vivo X-ray studies. SEM studies were performed to determine coating thickness and film topography.


RESULTS
In vitro studies revealed that the tablet with 10% coating level released the drug after 5 h lag time corresponding to the colonic region. Tablets with 10% coating level could maintain their integrity in human volunteers for 5 h, approximating colon arrival time and release the drug instantaneously.


CONCLUSIONS
Colon-targeting and instant drug release for 10% coating level was due to the dissolution of the Eudragit FS 30 D and the immediate release effect of superdisintegrant. It was observed that as the coating level increased, the lag time also increased. This was because of increased diffusion path length and tortuosity at higher coating levels.


CONCLUSIONS
An in vivo-in vitro study revealed that not only the sensitivity of the polymer to the pH environment but also the thickness of coating plays an important role in colon delivery and the tablet with 5% superdisintegrant and 10% coating level achieved the desired performance of the colon targeting.
Kshirsagar
Sanjay J
SJ
Department of Pharmaceutics, AISSMS College of Pharmacy, Pune 410001, Maharashtra, India. sanjayjk@rediffmail.com
Bhalekar
Mangesh R
MR
Umap
Rajesh R
RR
D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism; D004008:Diclofenac / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D008297:Male; D008855:Microscopy, Electron, Scanning / Q000379:methods; D011109:Polymethacrylic Acids / Q000737:chemistry; D011859:Radiography / Q000379:methods; D013608:Tablets, Enteric-Coated / Q000008:administration & dosage* / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D005079:Excipients; D011109:Polymethacrylic Acids; D013608:Tablets, Enteric-Coated; D004008:Diclofenac; C038300:methylmethacrylate-methacrylic acid copolymer