Ultra- sustained-release multi-particulate dosage form of Doxycycline as a platform of repurposing therapeutics in the fight against COVID 19: in-vitro and in-silico study

Purpose: Many recent studies highlighted Doxycycline beneficial multiple effects against SARS-COV2 either as a monotherapy or combination therapy. The creation of novel drug delivery systems is an attractive approach for the repurposing of drugs in a trial to fight COVID 19. In this study, ultra-sustained-release dosage forms were designed. Methods: A simple and cost-effective method was followed. Eudragit L100 (EL100), a pH sensitive water insoluble polymer, was combined with Doxycycline (DOX) in different ratios to form multi-particulate systems (MPs) with different drug release rates. Results: All the prepared MPs significantly sustained DOX release to reach a complete drug release after about 23.9, 142.57 and 165.58 h in case of MP1, MP2 and MP3, respectively compared to the pure drug which attained 100 % drug release within 30 min. The drug release was diffusion-dependent. Also, the prepared MPs showed satisfactory flow properties. The formula attaining the most extended drug release was subjected to characterization. In-silico molecular modeling study proved the high binding affinity of DOX/EL100 to S1-RBD of SARS-CoV-2. This high interaction may interfere with virus attachment to the host receptors and hence inhibit virus infection. Conclusion: This study shed the light on a possible platform to prepare ultra-long-acting dosage forms having different drug release rates by just simple, yet attractive, modifications which can offer promising therapeutic approaches.