Evaluation of the stability of morphine sulphate in combination with Instillagel.

BACKGROUND AND OBJECTIVE: The Pharmacy Department at the Western General Hospital in Edinburgh prepares a topically applied product in which morphine sulphate is incorporated into Instillagel for use in reducing pain associated with rectal and other cancers. A stability indicating method was required for assessment of the stability of this combination. METHODS: A gradient high performance liquid chromatography method was developed to assess stability and an LC-MS method was used to characterize the degradants from forced degradation of the components in the formulation. RESULTS AND DISCUSSION: The method was found to have acceptable inter- and intra-day precisions. Under all storage conditions investigated morphine sulphate remained within 98.1% and 103.2% of the initial concentration, lidocaine hydrochloride within 96.07% and 104.9% and chlorhexidine gluconate within 97.3% and 105.5%, except for samples stored at 37 degrees C beyond 240 h. A sample of the admixture was stored up to 7 months at 37 degrees C and was found to be reasonably stable with only the chlorhexidine concentration declining appreciably to 92% of the initial concentration. Some of the degradants of chlorhexidine and morphine were characterized by liquid chromatography mass spectrometry. It could be concluded that the admixture was stable for over 22 days at 4 degrees C protected from light, over 22 days at 25 degrees C exposed to normal light, and for 7 months at 37 degrees C protected from light. CONCLUSION: The components in the combination were found to have good long-term stability.

The chemical and pharmaceutical equivalence of sulphadoxine/pyrimethamine tablets sold on the Tanzanian market.

This study investigated chemical and pharmaceutical equivalence of 11 brands of pyrimethamine-sulphadoxine combination tablets sold on the Tanzanian market. Physical and chemical tests were performed for all the 11 brands. These tests included hardness test, friability, disintegration, dissolution, weight uniformity and assay for the active components. All the brands passed all the quality specifications of the United States Pharmacopoeia (USP) and British Pharmacopoeia (BP) in terms of hardness, friability, disintegration, assay and dissolution test, except for three brands that failed the hardness, disintegration or friability tests. One brand failed both the hardness and disintegration test; one failed the hardness test, whereas another one failed the friability test. The percentage content of pyrimethamine in the brands was in the range of 91.04-100.20% whereas that of sulphadoxine ranged from 91.53% to 99.88%. There were no major differences between the different brands of tablets containing pyrimethamine and sulphadoxine and the innovator product (Fansidar), and all brands were physically and chemically equivalent. The results indicate that the post-market surveillance and registration process in Tanzania is having an impact on product quality as there was no brand which could be considered of very poor quality. Impurity profiling of all the locally produced brands indicated that they all contained the same sulphadoxine impurity, which was absent in the innovator product, suggesting a common source of generic raw material.