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Aceclofenac (ACE) is a most commonly used drug for the relief of pain and inflammation associated with rheumatoid arthritis. The mean plasma elimination half-life of ACE is around 4 hrs and, therefore, frequent dosing is required which leads to patient noncompliance. Hence, to reduce the dosing frequency and adverse side effect, sustained release formulation of aceclofenac-loaded silica nanoparticles (ASiNPs) is beneficial to improve the patient noncompliance. Mesoporous silica nanoparticles (SiNPs) were prepared by precipitation method using tetra ethyl ortho silicate (TEOS) as a precursor. Response surface methodology (RSM) was used to optimise the independent variables such as SiNPs and 3-amino-propyl trimethoxysilane (APTMS) concentration, respectively, for dependent variables such as encapsulation efficiency (%EE) by using Design Expert software. The developed ASiNPs were characterized for their physiochemical properties. Results obtained from physiochemical characterisation confirmed the successful incorporation of drug in the SiNPs. The %EE was found to be in the range of 14.64–76.42%. In vitro drug release of ASiNPs in intestinal pH 6.8 shows sustained release up to 15 hrs compared to the pure ACE. From this study, we can conclude that ASiNPs would be able to sustain the drug release, reduced side effects and better patient compliance in combination with tablets and capsule. [ABSTRACT FROM AUTHOR]