Poor oral bioavailability is a major challenge affecting the new drugs reaching the market due to its low aqueous solubility. Nanosuspensions have the potential and rap-idly providing a platform solution to substantially increase dissolution rate, solubility with subsequent enhanced bioavailability via the oral route of administration of a range of poor water-soluble drugs. In this study cost effective simplest approach of precipitation combined with ultrasonication were utilized with aims to enhance the dissolution and hence the bioavailability of these selected drugs. Nanosuspensions of aceclofenac (AC) and glimepiride (GLM) were fabricated in precipitation and precipitation ultrasonication method. Stable nanocrystals of AC and GLM with particle size 112.0±2.01 nm and 152.4±2.42 nm with narrow polydis-persity index (PDI) (0.16±0.01) and (0.23±0.01) respectively, were produced in less than one hour using hydroxypropylmethyl cellulose (HPMC 6cps) (1.0%), PVP-K30 (1.0% w/v) and SLS (0.12% w/v) as stabilizers/particles growth inhibitors. Similarly, the batch sizes were successfully scale up from 5ml to 400 ml for AC and from 5 ml to 300 ml for GLM with no significant increase in the mean particle size and PDI were observed. The crystallinity of the processed AC and GLM was confirmed using DSC (Differential scanning calorimetry) and P-XRD (powder x ray diffraction). The satu-ration solubility of the AC and GLM nanocrystals were substantially increased. The solubility of AC nanocrystals were increased to (752.4± 2 μg/mL) compared to the AC in water (171.4 ± 1.3 μg/mL) and stabilizer solution (358.3± 2.0 μg/mL), whereas for GLM the solubility of nanocrystals were increased to (900±1.8 μg/mL) and (684.6 μg/mL± 2.0) respectively, compared to the raw AC and GLM in water (145.0 ± 2.3 μg/mL) and (56.35 μg/mL ± 1.85) respectively and in stabilizer solution the sol- ii ubility were (300.0± 2.0 μg/mL) and (248.2 μg/mL ± 2.7) respectively. The physical stability studies of AC and GLM were conducted for 90 days at different storage tem-peratures including, 2-8°C, 25°C and 40°C, demonstrated that nanocrystals stored at 2-8°C and 25°C were most stable compared to the samples stored at 40°C. Similarly, AC and GLM nanocrystals showed enhanced dissolution rate compared to unpro-cessed, micronized and their marketed counterparts. The in-vivo studies conducted in rabbits (as animal model) of both AC and GLM nanosuspensions resulted in signifi-cantly greater Cmax and AUC compared to unprocessed drug. The liquid nanosuspen-sions of both selected drugs were incorporated as granulating fluid into other excipi-ents for conversion to solid dosage form (tablets). Prepared granules were tested for flow parameters and satisfactory results showed. The compressed tablets were evalu-ated for weight variation, disintegration, hardness, % assay, in-vitro dissolution and finally stability studies. In summary, the study demonstrates that both standard crystallization com-bined with ultrasonication are effective in producing stable nanocrystals with smallest particle sizes and enhanced dissolution rate, while controlling the key experimental and process conditions. The tablets prepared using nanosuspension as granulating agent in AC and GLM showed marked improvement in in-vitro dissolution when compared with using raw drug in the formulation