A Comparative Study on Dissolution Enhancement of Acetaminophen by Cooling, Anti-solvent, and Solvent Evaporation Crystallization.
2017
The aim of this study was to prepare APAP crystals by cooling, anti-solvent, and solvent evaporation crystallization to enhance its dissolution rate and to make comparisons of the three methods. Agitating speeds and types were regarded as factors affecting crystallization procedure. Samples were made with different ratios of PEG4000. They were characterized by X-ray diffraction and scanning electron microscopy. Dissolution tests were conducted to assess their dissolution property. The proportions of carriers existing in crystals by cooling and anti-solvent crystallization ranged from 1.3 to 5.1%. Mean dissolution time (MDT) of samples by the two methods was about 3 min, which was 17.2 min for untreated APAP. Addition of too much PEG4000 in solvent evaporation crystallization could decrease dissolution rate of APAP. Samples agitated by a rotor with speed of 100, 500, and 1000 rpm dissolved faster than those by a high shear mixer with speed of 3400 and 5000 rpm or by a glass rod. Agitating speed and type could affect particle size and drug dissolution. Dissolution enhancement of APAP might be attributed to decrease of fine particles and increase of particle wettability.
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