Preparation Of New Dosage Forms Of Paracetamol Using Supercritical Anti-solvent Process

Paracetamal also called acetaminophen,is the preferred antipyretic analgesics for the world health organization.Children and adults all can use because of its fast oral absorption and no damage to liver in normal dose.However,the application is limited by its weakness,including lack of drug dosage forms,incomplete specification,et al.Experimental and clinical studies found that cocrystal and loaded drugs could control the particle size distribution,improve drug?s solubility,increase drug?s tensile strength and control its release,which improves the medicinal value.In this paper,trimethylglycine（TMG）and hydroxypropylmethyl cellulose phthalate（HPMCP）were selected as coformer and carrier material respectively,the corresponding solvent systems were methylene chloride/methanol（DCM/Me OH）,methylene chloride/ethanol（DCM/EtOH）,respectively.And L₁₆（4⁵）orthogonal experiments were designed to prepare and optimize paracetamol cocrystal or loaded microsphere via supercritical anti-solvent process（SAS）.Samples were characterized with SEM,FT-IR,XRD,Raman,DSC and TG to investigate the influence on particle size,morphology,et al.While TMG as the coformer,DCM/MeOH as the solvent system,according to the orthogonal array design,the significant sequence influence of 5 process parameters on drug content（DC）is P>F>VR>C>T.The optimal operating condition is VR（MeOH/DCM,v/v）=0.5,C=30 mg/ml,F=1.2 mL/min,P=100 bar,T=45 ^oC.SEM and particle size results showed that PCA-TMG cocrystal has variety of crystal habits.XRD and DSC results suggested formation of cocrystal.In vitro release results showed that the cocrystals improved the release performance.Stability results suggested that the cocrystals provided good physical stability under different conditions.While HPMCP as the carrier,DCM/EtOH as the solvent system,the influence of all parameters on encapsulation efficiency（EE）is T>C>F>P>VR,and the optimal operating condition is VR（EtOH/DCM,v/v）=3:10,C=7 mg/m L,F=0.5 m L/min,P=100 bar,T=50^oC.SEM and particle size results showed that paracetamol loaded microspheres by SAS were smooth and uniform particle size.XRD and DSC results suggested paracetamol was firmly loaded in the carrier material with amorphous form.In vitro release results showed that the loaded microspheres had good performance.Stability results suggested that loading paracetamol into carrier material provided good physical stability under different conditions.