Characterization of impurities formed by interaction of duloxetine HCl with enteric polymers hydroxypropyl methylcellulose acetate succinate and hydroxypropyl methylcellulose phthalate

Journal of Pharmaceutical Sciences

Volumn 87, Issue 1, 1998, Pages 81-85

  Jansen, Patrick J ^a   Oren, Peter L ^a   Kemp, Craig A ^a   Maple, Steven R ^a   Baertschi, Steven W ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DULOXETINE; HYDROXYPROPYLMETHYLCELLULOSE ACETATE SUCCINATE; HYDROXYPROPYLMETHYLCELLULOSE PHTHALATE; POLYMER;

ARTICLE; DRUG DEGRADATION; DRUG FORMULATION; DRUG IMPURITY; DRUG STABILITY; DRUG STRUCTURE; ENTERIC COATED TABLET; HEAT; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY;

EID: 0031937876     PISSN: 00223549     EISSN: None     Source Type: Journal    
DOI: 10.1021/js970133r     Document Type: Article

References (7)

1. Wong, D. T.; Bymaster, F. P.; Mayle, D. A.; Reid, L. R.; Krushinski, J. H.; Robertson, D. W. Neuropsychopharacology 1993, 8, 23-33.
2. Bopp, R.J.; Breau, A. P.; Faulkinbury, T. J.; Heath, P. C.; Miller, C.; Stephan, E. A.; Weigel, L. O.; Wong, D. T. The Rearrangement of Duloxetine Under Mineral Acid Conditions. Presented at the 206th National American Chemical Society Meeting, San Diego, CA; March 13, 1993; ORGN 111.
3. The level of the impurity was measured to be 0.3% in a sample stored at 30 °C/60% relative humidity for 12 months and 3.6% in a sample stored at 40 °C/75% relative humidity for 6 months.
4. Information obtained from product literature supplied by the manufacturer of HPMCAS. According to the manufacturer's certificate of analysis, the HPMCAS contained 0.06% free succinic acid and the HPMCP contained 0.57% free phthalic acid.
5. 2 (calculated 398.1426, found 398.1458); 3 (calculated 446.1426, found 446.1416)
6. Dorman, D. E.; Bovey, F. A. J. Org. Chem. 1973, 38, 1719-1721.
7. This corresponded to a molar ratio of methylamine to duloxetine of ∼450:1.