Drug-drug/food interactions are major source of patient’s inconvenience and non-adherencernthrough disruption in a patient’s daily schedule. Hence, lack of knowledge of potentiallyrnsignificant drug-drug/food interactions lead to poor clinical outcomes. Thus, investigationrnof different incompatibilities of drugs using spectroscopic techniques is mostrnimportant inquiry of solving these problems. For this reason, the optical transition probabilitiesrnand interactions of some drugs (nicotinamide (NIC), neomycin sulfate (NOMS),rnnorfloxacin (NOR) and ciprofloxacin (CIP)) with biologically active compounds of coffeernbeans (chlorogenic acid (CGA) and caffeine (CAF)) have been investigated usingrnUltraviolet visible (UV-Vis) absorption and fluorescence spectroscopic techniques. Fromrnthe UV-Vis spectroscopic technique, the self-, hetero-association, thermodynamic properties,rnand optical transition probabilities of the drugs were investigated in aqueous solution.rnThe parameters were analysed using Dimer model and Bensi-Hildebrand equationsrnrespectively for the self-and hetero-associations. The obtained equilibrium dimerizationrnconstant (KC) values are 2.379 _ 104, 1.06 _ 105, 5.424 _ 103, 4.377 _ 103, 4.3135 _rn103 and 6.67 _ 103MÀ€€1 for NIC, NOMS, NOR, CIP, interaction of nicotinamide withrnchlorogenic acid (NIC-CGA), and interaction of norfloxacin with caffeine (NOR-CAF)rnrespectively. In order to understand the interaction mechanisms of the self and heteroassociations,rnthermodynamic properties were determined using Vant’s Hoff’s equation.rnThe molar enthalpy changes were found to be 4.826_0.415, 3.76_0.66, ð€€€(5.35_0.459),rnð€€€(1.98 _ 0.25),ð€€€(16.927 _ 0.836) and ð€€€(1.277 _ 0.103)kJ.molð€€€1 for NIC, NOMS, NOR,rnCIP, NIC-CGA and NOR-CAF respectively. Thus, hydrophobic interactions are dominantrnfor the interaction of NIC and NOMS molecules, and electrostatic forces play thernmajor role in the interactions of NOR, CIP, NIC-CGA and NOR-CAF molecules. The op-rn(Copyright C Ataklti Abraha June 22, 2018) virnviirntical transition probabilities of the drugs were determined using integrating absorptionrntechnique from the absorption spectra of the drugs. The values of the oscillator strengthsrnare 0.07, 0.1,0.37 and 0.46 for NIC, NOMS, NOR and CIP respectively. Besides, the bindingrnof CAF with NIC using fluorescence quenching technique was analysed at temperaturesrnof 295 and 303 K and it was confirmed with the absorption spectra of the bindingrnmolecules. From this fluorescence quenching spectral analysis the quenching constantrn(1.775_104L/mol), quenching rate constant (5.052_1013L/mol/s) and number of bindingrnsites 0.88 were determined at 295 K. The thermodynamic properties of interaction ofrnnicotinamide with caffeine (NIC-CAF) indicates that electrostatic forces play the majorrnrule in the binding of the molecules. The effect of solvent polarity on the absorption andrnfluorescence spectra of NIC were investigated. The ground state and excited state dipolernmoments of NIC are estimated from solvatochromic shifts of absorption and fluorescencernspectra as a function of the dielectric constant and refractive index functions. Thus, thernground and excited dipole moments were found to be 0.02D and 0.268D respectively usingrnBilot-Kawski method. The excited state dipole moment is found to be higher thanrnthose of ground state for all of the used methods, and the higher values are attributedrnto more polar excited state of NIC. Therefore, the results of the study are very importantrnfor understanding the binding reaction in biological system, nature and strength of therntransition, absorption spectral interpretation, and in providing stringent test of atomicrnand molecular structure calculations for theoretical work of the compounds. Thus, understandingrnthe interaction properties of the drugs may help in the field of pharma technologyrnand food companies in improving the efficiency and the capabilities of absorptionrnof the drugs in biological system and in induce rapid recovery of patient’s.