Pickering Emulsion For Overdose Acetaminophen Removal

Acetaminophen is one of the most commonly administered analgesic and antipyretic,however,intentional or accidental administration overdose of acetaminophen by oral route could lead to acute drug intoxication.In clinical,the blood concentration of acetaminophen after overdose beyond the therapeutic dose reaches 150 mg/L~ 200 mg/L within 0.5~ 4 hours,leading to acute intoxication.In emergency units,the common treatments for acute intoxication,such as patient-intolerable emetics,medicinal carbon adsorption and gastric washing,are risky,poorly efficient,expensive and hard to implement.In this study,an innovative oral emulsion was proposed for the removal of overdose acetaminophen.The active Pickering emulsion was prepared with the hydrophobically modified montmorillonite as the emulsifier,tributyl phosphate as the carrier,liquid paraffin as the oil,and sodium hydroxide as inner phases respectively.Acetaminophen was removed with the facilitation of TBP into the inner aqueous phase,forming acetaminophen sodium with NaOH,to achieve the purpose of removing overdose acetaminophen.Meanwhile,some acetaminophen was adsorbed inside the montmorillonite,with the adsorptivity of montmorillonite,to improve its removal performance with rapidity,safety and efficiency.In this reasearch,the hydrophobically modified montmorillonite particles,also namely organoclay particles(HMMT)were prepared by the ion exchange of di-ethyldimethylammonium chloride(DODMACl)as modifier and montmorillonite.The montmorillonite was successfully modified by FTIR,SEM and TEM characterization.The effect of modifier content on the contact angle of organiclay was investigated.With the increase of the modifier content,the contact angle increased,and the orgnoclay particle with the contact angle closed to 90° was determined to stabilize the W/O Pickering emulsion.The effects of NaOH concentration,TBP content,HMMT particle content,oil-water volume ratio and preparation temperature on the detoxification performance of acetaminophen were investigated.The effects of HMMT particle content,oil-water volume ratio and preparation temperature on the stability of the emulsion were investigated on the basis of the demulsification ratio,viscosity change and morphology of the emulsion.The optimum preparation condition of the emulsion for acetaminophen removal was determined by univariate analysis.Such detoxifying emulsion was prepared at 55 ℃ with 2% organoclay(HMMT)as the emulsifier,6% tributyl phosphate(TBP)as the extractant,and 0.1 mol/L NaOH as the inner phase in the volume ratio of 5:7.A relatively stable and homogeneous emulsion with 74 μm of average particle size was prepared with the above condition.0.5 g/L acetaminophen was reduced to 0.13 g/L in 2 minutes,lower than the intoxication content of 0.15 g/L,and the demulsification ratio is less than 3% within 2 h,performing a fast removal rate and good stability,Finally,the detoxification performance and stability of the emulsions prepared under the optimal conditions in simulated artificial gastrointestinal fluid were studied.The detoxification performance of acetaminophen with initial concentration of 0.5 g/L,1.0 g/L and 2.0 g/L in the artificial gastric fluid(SGF)was investigated.With the increase of the initial acetaminophen concentration,residual content of acetaminophen increased,and the initial concentration of 0.5 g/L acetaminophen decreased to 0.13 g/L in 6 min.The emulsion separated from the SGF was put into the artificial intestinal fluid(SIF)for in vitro stability investigation.The results showed that the leakage ratio was less than 4% in 10 h with good metabolic stability.The long-term stability of the prepared emulsion was investigated and stored for more than 10 months at 4 ℃.