| Hydroxypropyl methylcellulose(HPMC)is a 2-hydroxypropyl ether methylcellulose which is a semi-synthetic material and is a nonionic ether formed by partial methylation and partial hydroxypropylation of cellulose and it is white or off-white powder.It is widely used in sustained release or controlled release preparations because of its excellent properties not found in other excipients,such as cold water solubility,acid-base stability,good film formation and metabolic inertness.This experiment collected 4 batches of domestic and imported HPMC respectively.Solvent residue,polymer structure,degree of substitution,crystallinity,molecular weight,viscosity,gelation temperature,water content,appearance morphology,particle size,bulk density and specific surface area were characterized to find the difference between domestic and imported HPMC.The difference in the sustained-release effect of domestic and imported HPMC in sustained-release tablets was compared by the dissolution curve.And based on the results of the indicator characterization,the specific effects of domestic and imported HPMC on the sustained release effect were discussed,which provided research ideas and experimental basis for improving the quality standard of domestic HPMC.The chloroform residue was determined by gas chromatography-mass spectrometry and the results showed that no chloroform residue was detected in 8 batches of HPMC.Infrared and near-infrared,gas chromatography,X-ray diffraction and differential scanning calorimetry,gel exclusion chromatography-eighteen-angle laser scattering were used to determine the structural indicators:polymer structure,degree of substitution,crystallinity and molecular weight.The results showed that no difference in the infrared and near-infrared spectra of the 8 batches of HPMC.The hydroxypropoxyl content of the domestic manufacturer’s 4 batches of HPMC were 7.50%,7.61%,8.47%,8.78%,and the molecular weight were 3.97×10~5,6.76×10~5,4.26×10~5,7.03×10~5respectively;corresponding to the import manufacturer the hydroxypropoxyl content were 8.52%,8.85%,8.92%,9.39%,the molecular weight were 4.36×10~5,7.22×10~5,4.27×10~5,6.98×10~5.In terms of crystallinity,two of the domestic batches have two peaks at 2θ=31.65°,45.35°and the rest are diffuse peaks.It can be seen that there were differences in the degree of substitution,crystallinity and molecular weight between domestic and imported HPMC.The rotational viscosity meter,gelation method and Karl Fischer meter were used to determine the viscosity percentage,gelation temperature and water content.The results showed that the percentage of viscosity of the domestic manufacturer’s 4 batches of HPMC were 106%,99%,105%,100%,and the water content were 2.9%,3.27%,3.39%,3.55%respectively;corresponding to the import manufacturer the percentage of viscosity were 89%,77%,89%,78%,the water content were 2.94%,4.41%,3.69%,4.01%,and 8batches of HPMC have no difference in gelation temperature.Scanning electron microscopy was used to determine its appearance.The results showed that the domestic manufacturer of HPMC was round,while the imported manufacturer HPMC was in the form of flakes.The specific surface area,particle size and bulk density were measured by a specific surface area measuring instrument,a laser particle size analyzer and a bulk density measuring device.The results showed that the specific surface area of the domestic manufacturer’s 4 batches of HPMC were 0.2199,0.2256,0.2783,0.2966 m2·g-1,and the bulk density were 0.3965,0.4096,0.3517,0.3340 g·mL-1,respectively;corresponding to the import manufacturer the specific surface area were 0.5051,0.4185,0.4533,0.4132 m2·g-1,and the bulk density were 0.2600,0.2531,0.2741,0.2439 g·mL-1;The results of particle size distribution showed that about small-size products imported HPMC has a wider distribution area than domestic.In summary,there were differences in viscosity,water content,appearance,specific surface area,particle size and distribution and bulk density between domestic and imported HPMC.In this study,one batch of domestic and imported HPMC was applied to the sustained release tablets of diclofenac sodium,and the difference in sustained release effect was compared by measuring the dissolution curve and disintegration.The results showed that in the pH 6.8 and pH 7.4 buffers,the release amount of domestic HPMC compressed sustained-release tablets reached about 70%at 2 h and the tablet disintegrated at 1 min,while the release amount of imported HPMC was about 20%,and there was no significant change in the tablets at 1 min,indicating that the sustained release effect of domestic HPMC was poor.The single influencing factor of HPMC was controlled to suppress the sustained release tablets,and the effect of the difference between the domestic and imported HPMC on the sustained release effect was determined by comparing the dissolution curves.The experiment results showed that when the methoxyl content was low,the hydroxypropoxy group content was high,the viscosity was large,and the smaller particle size of product was more,it will has a better sustained release effect.This experiment established the evaluation method of the key quality attributes of HPMC,and compared the difference of the quality index and its sustained release effect between domestic and imported HPMC.Through the single factor impact experiment,the relationship between the key quality properties of HPMC and the sustained release effect of sustained release preparation were established,which provided a theoretical basis for controlling the quality standard of HPMC. |
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