Shahul Hussain Shaik*1, Dr. S.N. Sri Harsha2, D. Yashwanth kumar3, K.S.S.N. Neelima4, B. Poornima chandran
Department of Pharmacy NIMS University, Jaipur
PACIFIC University, Udaipur, Rajasthan
Krishna Chaitanya Institute of Pharmaceutical Sciences, Madanapalli
*E-mail: [email protected]
Targeted drug delivery to colon is highly desired for the treatment of diseases such as colon cancer, IBD, Crohn’s disease etc., and for the systemic delivery of proteins and peptide drugs. A colonic drug delivery system is expected to protect the drug during the transit time in the GIT and to allow its release only in the colon. The objectives of the present project are to investigate the colon specificity of polysaccharides in synthesis of prodrugs and in formulations. The polysaccharides as polymer are mainly used to carry the drug moiety to the colon both in prodrug concept and formulation. Two prodrugs (Ibuprofen-β-cyclodextrin and Budesonide -β-cyclodextrin) have been synthesized and investigated. They were found to be colon specific, though, the yield was found to be very poor. From the IN-VIVO study they were also found to be very effective. As far as the formulations with polysaccharides are concerned, a novel polymer khaya gum was investigated for its colon specificity and compared with a well established polysaccharide polymer guar gum. It was found that the polysaccharides are very effective for targeting the drug to colon provided they are further coated with enteric polymer. Further, the present investigation also revealed that the effect of solubility of the drugs on the colon specificity of the polysaccharides. The weakly basic drug being very soluble in the acidic pH and the hydrophilic nature of the polysaccharides leads to release the drug in the stomach to greater extent compared to a drug molecule which is poorly soluble in the acidic pH. The investigation revealed that the prodrugs of drug molecules with polysaccharides are better colon specific compared to the formulations prepared with the polysaccharides. This is because the hydrophilicity nature of the polysaccharides releases the drug in the stomach to some extent especially weakly basic drugs. However, they are very effective when coated further with enteric polymer. Prodrugs with polysaccharides, though soluble in the aqueous solutions, there is a need of enzyme system to break the covalent bond formed between the drug molecule and the polysaccharide. Hence, irrespective of the nature of the drugs, prodrug approach is better to target the drugs to colon compared to the formulations with polysaccharides.
Keywords: Prodrug, polysaccharide, khaya gum, guar gum, colon specificity.