ABSTRACT
OBJECTIVE： To synthetize the synthesis of mitoxantrone and evaluate its quality. METHODS： Crude product of mitoxantrone was prepared by slow oxidation of 1，4，5，8-tetrahydro-anthraquinone with N-（2-hydroxyethyl） ethylenediamine in water bath at 50 ℃ for 2 h under argon protection and in dry air for 4 h. The crude product was crystallized by ethanol-n-hexane （4 ∶ 1，V/V） mixture solution， which was cooled overnight and then washed by ethanol-n-hexane mixture for many times. The melting range， pH value of solution， ultraviolet-visible absorption spectrum， infrared structural characteristics， drying weight loss （water loss rate） and critical relative humidity （CRH） of the purified products （4 batches） were investigated. HPLC method was used to determine the contents of mitoxantrone. RESULTS： The mitoxantrone was prepared successfully， and synthetic yield of mitoxantrone was 34.3％； the melting point ranged from 159.1-163.6 ℃. The aqueous solution was alkaline （pH 7.63-9.54）； there was a maximum ultraviolet absorption peak at 235-245 nm； there was a maximum absorption peak of visible light at 590-600 nm； the infrared characteristics were consistent with those described of mitoxantrone in the 2015 edition of the Infrared Spectrum Collection of Drugs； water loss rate were －0.83％-2.36％； CRH value was 54.7％， and the average content of the product was 78.1％（n＝4） by HPLC method. CONCLUSIONS： The mitoxantrone is synthesized under mild， non-toxic and harmless experiment conditions. The synthesis step is simple， the cost is low and the yield is high. The quality of products meets the quality requirements.
ABSTRACT
Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles. The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 degrees C, crystallization pressure 12 MPa, PVP concentration 4 mgmL(-1), and CO2 velocity 3.5 Lmin(-1). Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 microm. IR and DSC analysis showed that PVP might complex with EC. The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect. Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.