3 full factorial design was used for the optimization . the levels for the selected independent variables y = b0 + b1x1 + b2x2 + b12x1x2 + b11x12 + b22 x22 on the basis of the preliminary trials a 3 full factorial design was employed to study the effect of independent variables i.e. drug - to - polymer - to - polymer ( x1 ) and the stirring speed ( x2 ) on dependent variables like particle size , drug entrapment efficiency , the time required for 50% drug release ( t50 ) and drug released up to 5 hr ( y5 ) and 12 hr ( y12 ) . the expected in vitro release pattern selected for the colonic delivery was not more than 10% of the drug release up to the end of small intestine ( 5 hr ) and more than 85% of drug release up to 12 hrs . in factorial design batches microspheres thus obtained were recovered from the medium and dried subsequently and stored properly for the further studies . the concentration of cross linking agent and stirring speed were varied in batches c1 to c9 . potential variables such as concentration of chitosan solution , polymers to drug ratio ( 2:1 ) and amount of dispersion medium ( 500 ml ) were kept constant . in vitro drug release studies in simulated gastro intestinal fluids showed a burst release pattern in the initial hour necessitating microencapsulation with eudragit s100 by solvent evaporation technique . the effect of different coat / core ratio on particle size , drug entrapment efficiency and in vitro drug release were studied . the microspheres of all the batches of the factorial design were spherical and free flowing . the average particle size of different chitosan microsphere formulations was found to be in the range of 9.93 m- 18.48 m and showed good correlation co - efficient ( 0.9932 ) . results indicate that the effect of x1 ( stirring speed ) is more significant than x2 ( amount of cross linking agent ) . when higher level of glutaraldehyde was used cross linking favoured and hence slower drug release was observed compared to the other batches . the entrapment efficiency of different formulations was found to be between 66.65 to 92.07% and showed good correlation co - efficient ( 0.9293 ) . the effect of stirring speed on entrapment efficiency showed that optimum speed should be 1000 rpm . in vitro dissolution of all the batches indicates that the burst release pattern in the initial hour . within 5 hr 70 to 90% of drug cumulative in vitro drug release of carvedilol from formulations c1 to c9 thus , only biodegradable polymers were not satisfactory for colonic delivery . the burst release may be due to solubility of chitosan in the acidic ph . in order to prevent the drug release in stomach and small intestine these chitosan microspheres were encapsulated with eudragit s100 , which shows solubility at a ph  7 . since formulation c4 showed high drug loading and drug release pattern , it is selected for microencapsulation process . chitosan microspheres ( c4 ) were microencapsulated with eudragit s100 to achieve colonic delivery of carvedilol . the effect of core - coat ratio on eudragit s100 microencapsulated chitosan microspheres was studied and found that the particle size was increased from 137.87 to 154.33 m with increasing the core - coat ratio from 1:8 to 1:12 . the entrapment efficiency of microencapsulated formulations varied between 90 - 95% with increasing core - coat ratio . the in vitro drug release studies of various eudragit coated chitosan microspheres were performed in simulated gastro intestinal fluids . results showed that 8 - 12% of drug was released within initial 4 hrs and increased thereafter when the formulations were exposed to ph which is above solubility of eudragit s100 . the best formulation then subjected to in vitro drug release in presence of rat ceacal contents . a result of release studies indicates that eudragit s100 coating offers a high degree of protection from premature drug release in the stomach and small intestine . eudragit coated chitosan microspheres deliver most of the drug load in the colon , an environment rich in bacterial enzyme that degrade the chitosan and allow drug release to occur at the desired site after proper transit time . thus , the designed formulation is potential systems as multiparticulate for the chronotherapy of hypertension .