| With the accelerated pace of modern life,social pressures increase,and people’s mental pressures also increase.The incidence of depression is rising rapidly,making it a common and frequently-occurring disease in modern society.It is predicted that by 2030,depression will become the second leading cause of disability besides cancer.Currently,the commonly used antidepressants are tricyclic antidepressants,monoamine oxidase inhibitors and reversible selective monoamine oxidase inhibitors,5-serotonin and norepinephrine reuptake inhibitors(SNRIs)[3].SNRIs drugs can significantly inhibit the 5-HT and the reuptake of NA,thereby increase the concentration of these two substances in the synaptic cleft,resulting in the effect of anti-depression.Desvenlafaxine Succinate(DVS)is a potent,selective 5-HT and NA reuptake inhibitor.This drug was developed by Wyeth pharms Inc.and currently it’s the most widely used prescription antidepressants in the world.Desvenlafaxine succinate sustained release tablets(DVS XR trade name:PRISTIO)is developed by the United States Wyeth,with usage and dosage for once a day.With the advantages of stable plasma concentration,low side effects and good clinical compliance,this prparation can ensure the clinical efficacy.Firstly,in this paper,a high performance liquid chromatography(HPLC)method for the determination of the content,release and related substances of DVS sustained-release tablets was established.The method was validated in details and the specificity,sensitivity,accuracy and durability of each method were confirmed.On this basis,the key quality properties of the original pharmaceutical preparations were fully analyzed,which provides a clear goal of development for the self-made products.Secondly,the prescription of the self-made product was studied on the basis of the prescription information and key quality properties of the original product.The compatibility test confirmed that the raw materials to be used have a good compatibility among raw materials.The particle size,flowability,compressibility,friability and coated tablet release curve(0.9%sodium chloride solution)were used as indexes to screen the types and amount of wetting agent and hypromellose(HPMC).The results showed that when ethanol was used as the wetting agent,HPMC K15M and K100M were used as the sustained-release matrix material,the tablets could be well prepared and achieve the desired release-inhibiting effect.On the basis of determining the composition of the prescription,the process parameters of preparation process were studied by small scale test and pilot scale up.The control ranges of the key parameters such as the granulation process,the drying process,the total mixing process,the tabletting process and the coating process were determined,which ensured the reproducibility of the preparation process and the industrialization production of the product.The in vitro release curve showed that the product had a significant sustained-release effect.And the release profiles had a good homogeneity between batches.The release behavior and the release curve fitting results of desvenlafaxine sustained-release tablets were consistent with that of the original preparations in various media.Finally,the quality and stability of three batches of pilot samples were studied.The results of the quality showed that the tablets had a good homogeneity between batches and all the quality indicators were consistent with that of the original preparations.The stability results showed that DVS sustained-release tablets were stable under the conditions of strong light and high temperature.But the moisture absorption was observed in high humidity condition,which indicated the DVS sustained-release tablets must be stored under seal.Accelerated test and long-time test results indicated that the DVS sustained-release tablets were stable in the commercially available package. |
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