Cellulose nanocrystals (CNCs) are charged nanoparticles with a high aspect ratio derived from the most common biological polymer, cellulose. Acid hydrolysis is one of the most common methods for CNC production. Whatman #1 filter paper was hydrolyzed by sulfuric acid and characterized by AFM in this research to examine the morphology and size distribution of CNCs. One drop of CNC suspension was air-dried on microscope cover glass to be analyzed by AFM with non-contact mode. The CNC dimensions were determined by measuring individual and isolated particles (n=88) via Nanosurf Easyscan2 software. The measurement data was analyzed by Excel statistically. Synthesized CNCs were ellipsoidal with the length, height, and aspect ratio of 219.87 ± 42.12, 6.25 ± 2.27, and 41.17 ± 21.70 nm, respectively. Although the length and height of the produced CNCs were in acceptable range, but the width of CNCs was an overestimation and it was not reliable, mostly due to AFM tip broadening effect. Particle size measurement of CNCs is a challenging process because of their rapid aggregation and rod shape. Although hydrolysis parameters are influential on the final shape and size of CNCs, but it is necessary to optimize and maximize the quality of sample preparation and AFM adjustment to obtain the size of CNCs with the most accuracy and reliability. The CNC dimensions were determined by AFM are slightly different in the literature but height (thickness) is the most reliable one based on this experiment. Further studies are required to standardize CNC size measurement by AFM.

Clarithromycin (CLA), a broad-spectrum macrolide, is a poorly soluble drug with dissolution rate limited absorption. The aim of this investigation was to prepare CLA nanoparticles from a ternary ground mixture in the presence of sodium lauryl sulfate (SLS) and polyvinyl pyrrolidone (PVP) as co-grinding water-soluble compounds, in order to improve the drug dissolution rate. Different weight ratios of CLA: SLS: PVP were ground in a dry process by planetary ball mill using different grinding ball size. Following the dissolution rate study, physical properties of the best dissolved co-ground formulation was studied. The accelerated stability studies were also conducted on the co-ground formulation.The results revealed that the dissolution rate of ternary ground mixtures was much higher than that of the intact drug (p<0.001). Decreasing the grinding ball size and weight with the same rotation speed resulted in particles with decreased dissolution. On the other hand, increasing the PVP concentration in the formulations reduced the drug dissolution. Dissolution efficiencies (DE10 and DE30) for the best dissolved formulation, which consisted of the equal ratio of each co-ground component, were 8.7 and 5 folds higher than the untreated CLA, respectively. This formulation formed nanocrystals with enhanced solubility after dispersing in water. X-ray diffraction, differential scanning calorimetry and infrared spectrophotometry confirmed no chemical interaction and phase transition during the process. Accelerated stability studies confirmed that the co-ground mixture almost remained unchanged in terms of dissolution rate, drug assay and particle size after exposing in stability conditions for three months.