CAS: 199191-66-7; (S)-Duloxetine Succinamide

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succinic acid anhydride duloxetine hydr°Chloride

📜丁二酸酐,盐酸度洛西汀置于三乙胺体系中,用 氯仿 用作溶剂,化学反应 0.25H,以200 Mg的收率获得4-[甲基[(3S)-3-(1-萘基氧基)-3-(2-噻吩基)丙基]氨基]-4-氧代丁酸
参考文献:Characterization Of Impurities Formed By Interaction Of Duloxetine Hcl With Enteric Polymers Hydroxypropyl Methylcellulose Acetate Succinate And Hydroxypropyl Methylcellulose Phthalate
标题:Characterization Of Impurities Formed By Interaction Of Duloxetine Hcl With Enteric Polymers Hydroxypropyl Methylcellulose Acetate Succinate And Hydroxypropyl Methylcellulose Phthalate
摘要:Duloxetine Hydrochloride ((S)-N-Methyl-3-(1-Naphthalenyloxy)-2-Thiophenepropanamine Hydrochloride) Has Been Found To React With Polymer Degradation Products Or Residual Free Acids Present In The Enteric Polymers Hydroxypropyl Methylcellulose Acetate Succinate (Hpmcas) And Hydroxypropyl Methylcellulose Phthalate (Hpmcp) In Dosage Formulations To Form Succinamide And Phthalamide Impurities,Respectively. The Rate Of Formation Of The Impurities Is Accelerated By Heat And Humidity. The Structures Were Deduced Using Molecular Weights Obtained From Lc-Ms Experiments And Confirmed By Comparison Of Uv Spectra,HPLC Retention Times,And Electrospray Mass Spectra To Independently Synthesized Material. It Is Proposed That Polymer-Bound Succinic And Phthalic Substituents Can Be Cleaved From The Polymer,Resulting In The Formation Of Either The Free Acids Or The Anhydride. It Is Postulated That The Reaction Is Enabled By Migration Of Either (1) The Free Acid Or Anhydride Or (2) The Parent Drug Through The Formulation. The Formation Of These Impurities Was Minimized By Increasing The Thickness Of The Physical Barrier Separating The Enteric Coating From The Drug.
Doi:10.1021/js970133R