RESUMO
Changes in structure of oral solid dosage forms (OSDF) elementally determine the drug release and its therapeutic effects. In this research, synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3D structure of enteric coated pellets recovered from the gastrointestinal tract of rats. The structures of pellets in solid state and in vitro compendium media were measured. Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media. Thus, optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media. The sphericity, pellet volume, pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for 2 h were recorded 0.47, 1.55 × 108 μm3, 0.44 × 108 μm3 and 27.6%, respectively. After adding pepsin and glass microspheres, the above parameters in vitro reached to 0.44, 1.64 × 108 μm3, 0.38 × 108 μm3 and 23.0%, respectively. Omeprazole magnesium pellets behaved similarly. The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3D structures to ensure better design, characterization and quality control of advanced OSDF.
RESUMO
OBJECTIVE:To establish a method for the simultaneous determination of 6 kinds of residual organic solvents in Omeprazole magnesium,such as methanol,isopropanol,acetonitrile,dichloromethane,ethyl acetate and toluenein. METHODS:Headspace GC was adopted. The determination was performed on the column of DB-624 column by temperature programming. The inlet temperature was 200 ℃,and hydrogen flame ionization detector was adopted with the temperature of 250 ℃;nitrogen gas was used as carrier gas with flow rate of 2.0 mL/min;the splitting-radio was 5 : 1,and sample size was 1 mL;the headspace tem-perature was 80 ℃ and the equilibrium time was 20 min. RESULTS:The linear range were 12.56-628.00 μg/mL for methanol(r=0.9997),20.22-1011.20 μg/mL for isopropanol(r=0.9999),1.96-97.76 μg/mL for acetonitrile(r=0.9997),3.10-154.88 μg/mL for dichloromethane(r=0.9998),20.69-1034.56 μg/mL for ethyl acetate(r=0.9998),and 3.53-176.72 μg/mL for toluene(r=0.9998);the limits of quantitation were 1.00,0.91,0.47,0.93,0.41 and 0.35 μg/mL respectively;the limits of detection were 0.31,0.30,0.14,0.31,0.12 and 0.11 μg/mL respectively;RSDs of precision,stability and reproducibility tests were lower than 3%;the recoveries were 94.53%-101.29%(RSD=2.15%,n=9),97.78%-103.42%(RSD=1.77%,n=9),96.99%-105.76%(RSD=2.59%,n=9),96.83%-102.05%(RSD=1.86%,n=9),97.98%-101.13%(RSD=0.88%,n=9)and 97.80%-102.40%(RSD=1.41%,n=9). CONCLUSIONS:The method is sensitive and accurate,can be used for the simultaneous determination of 6 kinds of residual organic solvents in Omeprazole magnesium,such as methanol,isopropanol,acetonitrile,dichloromethane,eth-yl acetate and toluenein.