Preparation and Characterization of Danazol Nanoparticles for Dissolution Improvement

Abstract

Danazol is a synthetic steroid used for endometriosis treatment, haslow bioavailability as it is practically insoluble in water. This study has been carried out to prepare and characterize danazol nanoparticles by nanoprecipitation method at a different polymer to drug ratios of 0.5:1,1:1,2:1 and 3:1 using different polymers of CMC-30 and various grades of HPMC and PVP,as stabilizers. Variables that might affect the particle size as polymer type,polymer to drug ratio,temperature of precipitation,addition rate of danazol solution,volume ratio,time of stirring,concentrationof drug,have been investigated. The particle size of the prepared formulas has been in the nano-sized except those using CMC and the best formula has beenF20 at a polymer to drug ratio of0.5:1 which has given the smallest particle sizeof 33nm.The investigations of the drug–stabilizer compatibility havebeen studied by FTIR and DSC,crystalline state by XRD,size,and shape of nanoparticles by FESEM and the results showed that there has been no interaction between the danazol and stabilizer and there has been a partial conversion of danazol from crystalline to an amorphous state with a size below 100nm. Most of the studied factors havebeen found affect the particle size of the nanoparticles.The Entrapment efficiency has been (91.3% ± 0.4) in the (F20). The solubility study revealed that 6.75,4.97 and 5.1 folds increased of solubility of danazol for nanoparticles than that for raw in distilled water,0.1N HCl and in phosphate buffer of pH 6.8.The simple capsule has been prepared by incorporation of freeze-dried of F20 with lactose as a filler and the in vitro dissolution study has been conducted using 0.1N HCl (pH 1.2) with 2% w/v Brij-35,phosphate buffer solution(pH 6.8) with 2% w/v Brij-35as dissolution media. Within 30 minutes,100% of the danazol has been released from the nanoparticle capsule in both dissolution media compared to the raw and physical blend capsules as controls havebeen nearly complete in 120 minutes.One can conclude that Antisolvent method is an easy,efficient method to prepare danazol nanoparticles with an intense effect on solubility and faster in vitro dissolution rate than raw drug and its physical blend with stabilizer.