Curcumin is a hydrophobic polyphenol isolated from dried rhizome of turmeric (Curcuma Longa Linn & zingiberaceae family), which is responsible for various pharmacological activities including anti-cancer, anti-oxidant, anti-bacterial, anti-fungal, anti-viral and anti-inflammatory and expected to have medicinal benefits in arthritis, psoriasis, diabetes, acquired immunodeficiency syndrome, cardiovascular diseases, multiple sclerosis, cancer and lung fibrosis.1,2 However, clinical usefulness of curcumin in the treatment of cancer is limited due to poor aqueous solubility, hydrolytic degradation in alkaline pH, metabolism via glucuronidation and sulfation in the liver and in intestine, and poor oral bioavailability. These limitations results in decreased therapeutic efficacy or absence of therapeutic efficacy in in-vivo studies.2 Though there are many novel approaches to overcome these limitations, nanotechnology (Particle size <1000 nm) is the most recent and offer significant improvement.3,4 Hence, to overcome these limitations we proposed to fabricate curcumin-piperine, curcumin-quercetin and curcumin-silibinin loaded polymeric nanoformulation. However, unfavourable combinations of drug-drug and drug-excipient may result in interaction, which leads to physical instability or chemical instability. Physical instability refers to changes in the characteristics of a drug that do not involve chemical bond formation or breakage in the drug structure, which can be identified by changes in the organoleptic parameters such as appearance, form etc. Chemical instability refers to changes in the chemical structure of the drug molecule resulting in drug degradation, reduced drug content and formation of other molecule such as degradation products. Both physical and chemical instability may cause safety concerns. Hence, a thorough drug-drug/drug-excipient compatibility study is mandatory.5 The present study was aimed to assess the physical and chemical instability of curcumin with various excipients to be used in the proposed nanoformulations.