Acta Poloniae Pharmaceutica ñ Drug Research, Vol. 67 No. 3 pp.299ñ306, 2010 ISSN 0001-6837 Polish Pharmaceutical Society Microencapsulation is used to modify and retard drug release. In pharmaceutical sustained release preparations, the uniqueness of microcap- sules lies in the wide distribution throughout the gastrointestinal tract. This potentially improves drug adsorption and reduces side effects related to local- ized build-up of irritating drugs against the gastroin- testinal mucosa (1). Nimesulide (NMS) is a non-steroidal anti- inflammatory drug (NSAID). It acts as a cyclooxy- genase-2 inhibitor (2). It also has other novel phar- macological features, which account for its effect in the control of pain and inflammation (3). Nimesulide attains peak serum concentrations of 1.98 to 9.85 mg/L within 1.22 to 3.17 h when given orally and extensively binds to plasma proteins (99%) having half-life 1.56 to 4.95 h, which requires frequent higher dosing to maintain plasma concen- tration (4, 5). Tizanidine (TZN) is a 2-adrenergic agonist and centrally active myotonolytic skeletal muscle relax- ant with a chemical structure unrelated to other mus- cle relaxants. It is a new treatment for spasticity associated with multiple sclerosis, stroke and back bone injury (6). The beneficial effects of administer- ing TZN in a controlled release formulation have been developed and presented by Smith in their clin- ical studies regarding spasticity and disability (7). Ethyl cellulose (EC) is a non-biodegradable and biocompatible polymer. It is one of the exten- sively studied encapsulating materials for the con- trolled release of pharmaceuticals and was selected as the retardant material for NMS and TZN. Several researchers have investigated the utilization of ethyl FORMULATION OF TWO-DRUG CONTROLLED RELEASE NON- BIODEGRADABLE MICROPARTICLES FOR POTENTIAL TREATMENT OF MUSCLES PAIN AND SPASM AND THEIR SIMULTANEOUS SPECTROPHOTOMETERIC ESTIMATION SHUJAAT A. KHAN, MAHMOOD AHMAD, GHULAM MURTAZA*, MUHAMMAD N. AAMIR, NAVEED AKHTAR, and ROZINA KOUSAR Department of Pharmacy, Faculty of Pharmacy and Alternative Medicines, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan Abstract: The objective of this study was to formulate stable and controlled release microparticles for simul- taneous delivery and UV spectrophotometric detection in combined dosage of an non-steroidal anti-inflamma- tory drug (NSAID) (Nimesulide, NMS) and a spasmolytic agent (Tizanidine, TZN) to maintain plasma con- centration 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 spec- tra 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 5.0ñ30.0 µg/mL of NMS and 0.5ñ3.0 µg/mL of TZN. The microparticles have a potential for the prolonga- tion 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. Keywords: coacervation, ethyl cellulose, microparticles, nimesulide, tizanidine 299 * Corresponding author: e-mail: gmdogar356@gmail.com; phone: +92-62-9255243