Research Article Development of Eudragit RS 100 Microparticles Loaded with Ropinirole: Optimization and In Vitro Evaluation Studies Prince Muhammad Kashif, 1 Asadullah Madni, 1,2 Muhammad Ashfaq, 1 Mubashar Rehman, 1 Muhammad Ahmad Mahmood, 1 Muhammad Imran Khan, 1 and Nayab Tahir 1 Received 9 August 2016; accepted 24 October 2016 ABSTRACT. The current study aimed to develop novel pH independent microparticles loaded with ropinirole (ROP) for sustained drug release. Eudragit RS 100 was used as release retardant and microparticles were fabricated by oil-in-oil emulsion solvent evaporation method. A three-factor three-level Box-Behnken design using Design-Expert software was employed to optimize formulation variables. Ropinirole loaded microparticles were evaluated with respect to morphology, particle size, encapsulation efficiency, and in vitro release profile. Optical microscopy and SEM micrographs indicated spherical shape with smooth surface and well-defined boundary. The particle size was in the range of 98.86 to 236.29 μm, being significantly increased with increasing polymer concentration. Higher polymer load also increased the thickness of internal polymer network, which led to reduced drug loss and higher entrapment efficiency (89%). The cumulative in vitro release was found to be in the range of 54.96 to 99.36% during the release studies (12 h) following zero order release kinetics and non-Fickian diffusion pattern. The developed microparticles have the potential to sustain the release of ropinirole, which may lead to a reduction in its adverse effects and improved management of Parkinson’s disease. KEY WORDS: Box-Behnken design; emulsion solvent evaporation; Eudragit RS 100; microparticles; ropinirole. INTRODUCTION Ropinirole HCl (ROP), an orally active non-ergot dopaminergic receptors (D2/D3) agonist, is considered a drug of choice in the management of Parkinsonism and restless legs syndrome (RLS) (1,2). ROP is rapidly absorbed from the gastrointestinal tract with a reported bioavailability of about 50% with very low plasma protein binding 10–40% (3). It is excreted through the urine with t 1/2 elimination half-life of about 6 h (4,5). Parkinson’s disease (PD) is the world’s second most common neurodegenerative condition related to the deple- tion of dopamine (6). It is estimated that about 1% of the global population of the age above 60 is being affected by PD (7). PD involves the death of dopaminergic neurons of substantia nigra pars compacta resulting in the imbalance of normal levels of dopamine and acetylcholine (8,9). The characteristic sign and symptoms of PD include anxiety, tremors, muscle rigidity, dementia, bradykinesia, depression, postural instability, and sleep disturbances (10). Encapsulation has been widely accepted technique to control release behavior, protect the properties, and im- prove the stability of capsulated core material by shielding from external environment (7,11). Several techniques have been adopted for the development of microparticles such as conservation, solvent evaporation, spray drying, fluidized bed technique, interfacial polymerization, and supercritical fluid expansion (12,13). Emulsification solvent evaporation (ESE) technique has attracted the attention because it is easy to fabricate, does not compromise the activity of drugs, and require room temperature and stirring rate (14). Oil in oil (O/O) ESE technique is more suitable for encapsulation of hydrophilic molecules to avoid the diffusion of drugs to the continuous phase during emulsification. Furthermore, the polar organic internal phase employed in oil in oil ESE technique ensures the solubility of hydrophilic molecules (15). Polymethacrylates (Eudragits), among the wide range of polymers (polyesters, poly (ortho esters), polyphosphazenes, polyanhydrides, polymethacrylates, polysaccharides), are pre- ferred for the development of microparticles by emulsion solvent evaporation technique because of biocompatibility, excellent stability, easy handling, and low cost (16,17). 1 Department of Pharmacy, Faculty of Pharmacy & Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, 63100, Punjab, Pakistan. 2 To whom correspondence should be addressed. (e-mail: asadullah.madni@iub.edu.pk; asadpharmacist@hotmail.com) AAPS PharmSciTech ( # 2016) DOI: 10.1208/s12249-016-0653-5 1530-9932/16/0000-0001/0 # 2016 American Association of Pharmaceutical Scientists