Development and validation of the analytical methods for determination of bromhexine hydrochloride and related impurities in novel orodispersible tablets
M. Strozik, M. Strzebońska, Katarzyna Skiba, Wiktor Tatara
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引用次数: 1
Abstract
Bromhexine hydrochloride (BRX) is widely applied as an active pharmaceutical ingredient of oral solutions and tablets for the treatment of the infections of the respiratory tract. However, fulfillment of the present regulations, required for the registration process of BRX, might constitute a challenge, due to the occurrence of (3RS)-6,8-dibromo-3-cyclohexyl-3-methyl-1,2,3,4-tetrahydroquinazolin-3-ium, specified as impurity E by European Pharmacopeia. To overcome this issue, a novel BRX orodispersible tablets (ODT) with improved chemical stability were developed that contain low level of impurity E. Herein the analytical methods, elaborated for the determination of BRX and the related impurities in this product are presented. Stability of the product was tested at accelerated (ACC), intermediate (INT) and long-term (LT) conditions for ICH zones II and III. The degradant E was the most common impurity detected. In the samples stored in INT and LT conditions only a slight increase in the impurities and a slight drop in the assay of the BRX was observed, however the results did not exceed the pre-established acceptance criteria. In the samples stored at ACC conditions, an increase of the known impurities, including degradant E, degradant B and N-oxide, was noted. Noteworthily, even after three years of the product’s shelf-life, the level of the degradant E is still below 0.2 % which corresponds to the ICH identification threshold for the BRX related impurities.
期刊介绍:
The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General.
A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.