Biopharmaceutical and marketing evaluation of diosmin- and hesperidin-containing products on the Bulgarian market

Introduction Diosmin and hesperidin are commonly used flavonoids in the therapy of vascular diseases. Aim This study aimed to present an independent evaluation of the market status, quality and biopharmaceutical characteristics of diosmin- and hesperidin-containing oral tablet-products (DHCPs) on the Bulgarian market. Materials and Methods Seven products, among which medicines (used as reference) and food supplements, with sustainable or growing market were selected for the survey: Detralex 500 mg, Phlebodia 600 mg, Dioket 600 mg, Novarix 650 mg, Asketon 500 mg, Venocode and Dih max 1000 mg. Sales analysis for 2016, 2017 and 2018 (year-to-date) was done with the kind support of Iqvia TM. All products were subjected to European Pharmacopoeia (EP) tests for tablet quality - disintegration, resistance to crushing, uniformity of mass and uniformity of dosage units. Biopharmaceutical profile regarding tablet drug release and dissolution potency was investigated on EP Apparatus 2 (Paddle method). Results Although all products were found to almost fully fulfill the EP criteria, extremely unsatisfying drug release was established in all tested media (pH 1,5, pH 4,5 and pH 7,2), reaching not more than 1.6% of the labeled content after 24 hours for the best performing products - Novarix and Venocode. Conclusion These results were not surprising considering diosmin and hesperidin`s water insolubility and respective low bioavailability. However, it would be reasonable to approach these two bioactive compounds technologically in preformulation stage in order to improve their solubility and therapeutic potency.