Comparative in vitro dissolution profiling with assay and content uniformity analysis of fingolimod for relapsing multiple sclerosis: An approach enhanced by AGREEprep and BAGI methodologies

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Abstract The use of fingolimod as a treatment for multiple sclerosis relapses is crucial in reducing disease activity, reducing relapses, and slowing down neurological impairment. A basic and efficient isocratic reverse-phase HPLC technique was designed and optimized for the quantitative analysis of Fingolimod under controlled chromatographic conditions in support of its critical clinical value. The separation was done under ambient temperature in a C18 column (250 × 4.6 mm, 5 µm) using a mobile phase, which consisted of 45% 0.05 M KH 2 PO 4 (pH 6.8) and 55% ethanol to ensure high retention and symmetry of the peaks. The process worked with a flow rate of 1.5 mL min −1 and UV detection of 210 nm, and 100 µL injection volume. The chromatographic system was allowed to equilibrate for 60 min so that the baseline could stabilize and consistent retention was achieved. An in-vitro dissolution comparison study identified that the test and reference products were very similar with a similarity factor f2 = 81 and a difference factor f1 = 2, which proved bio-relevant performance similarity. The excellent acceptance value (AV) of 2.4 was obtained by content uniformity testing which was within the pharmacopeial range. The method's linearity was excellent in the concentration range of 0.25–1.5 μg mL −1 with a r = 0.9999 whereas accuracy and recovery fell within a range of 100.14 percent to 101.07 percent indicating high reliability of the method in routine quantitative work. Forced degradation was studied in the presence of acid, base, oxidative, photolytic, and thermal stresses. Fingolimod was discovered to be unstable in all the degradation pathways tested, and so, it must be protected and not subjected to stressful conditions to avoid degradation. AGREEprep was used to assess the greenness of the method with a score of 0.6 and BAGI was used to evaluate the analytical eco-score with a score of 82.5, which confirmed that the method has a positive environmental footprint compared to other conventional HPLC methods. All in all, the devised method is accurate, precise, stable-indicating, environmentally thoughtful and appropriate to complete quality-assessment tests of Fingolimod preparations in dissolution profiling, assay, and content uniformity analyses.

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