Dissolution rate enhancement of clarithromycin using ternary ground mixtures: nanocrystal formation

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.