The objective of this study was to formulate stable and controlled release microparticles for simultaneous delivery and UV spectrophotometric detection in combined dosage of an non-steroidal anti-inflammatory drug (NSAID) (nimesulide, NMS) and a spasmolytic agent (tizanidine, TZN) to maintain plasma concentration that may increase patients compliance, improved therapeutic efficacy, The aim was also to reduce severity of upper GI side effects of NMS because of alteration in delivery pattern via slow release of drug from microparticles and to increase the benefits of spasticity and disability for spastic patients by administering TZN in a modified release formulation as these two drugs are often prescribed in combination for the management of pain associated with muscles spasm. Ethyl cellulose was used as a retardant polymer. Drug-polymer and drug-drug compatibility study were conducted by different analytical tests. Microparticles were prepared by coacervation thermal change method. The prepared microparticles were characterized for their micromeritics and drug loading. The prepared microparticles were light yellow, free flowing and spherical in shape. The drug-loaded microparticles showed 87% and 91% entrapment efficiency of NMS and TZN, respectively, and release was extended up to 10 h. The infrared spectra, differential scanning calorimetry thermograms and XRD spectra showed the stable character of both the drugs in the drug-loaded microparticles. The in vitro release study of microparticles was performed in phosphate buffer pH 6.8. Linearity was observed in the concentration range of 5.0-30.0 microg/mL of NMS and 0.5-3.0 microg/mL of TZN. The microparticles have a potential for the prolongation and simultaneous delivery of the NIM and TIZ. The proposed UV method for simultaneous detection can be used for routine analysis of combined dosage form.