ABSTRACT
After the global pandemic of the new coronavirus, its rapid spreadand many victims, it is necessary to find an effective vaccine or drugs to overcome it. Most specialists consider that repositioning somemedications is the best, fastestand most reliable option for treating patients with the new coronavirus without delay. One of these drugs was an old antimalarial drug, hydroxychloroquine. The current review aimed to explore its potential mechanism, as well as its pharmacokinetics and toxicity, in an attempt to suggest a treatment protocol for its use in treating the COVID-19 virus effectively and safely. This study reviewed the published references on the popular search engines as well as the reference books regarding the pharmacological effects of HCQ.The results of this study suggested the following practical guidelines to optimize HCQ efficacy and safety in the management of COVID-19. HQC should be used as early as possible, i.e., once the viral infection is confirmed or suspected. A loading dose is recommended to be given in 3-4 divided doses to minimize cardiac toxicity. Maintenance daily dose (divided into two doses), should be continued until complete remission. Precautions,drug-interaction, contraindications, variable metabolic pathways in the particular population should be considered. This study suggests more clinical trials regarding the use of HCQ in the management of early identified COVID-19 patients under close medical observation to minimize HCQ cardiac toxicity
ABSTRACT
Sulindac is a poorly soluble nonsteroidal anti-inflammatory drug associated with gastrointestinal intolerance as its serious side effect. This work investigated the ability of Eudragit Ll00-55 (Eud L100-55), Cellulose acetate phthalate (CAP) and β-cyclodextrin (β-CD) to ameliorate its gastric ulcers induced in rats. Binary solid dispersions (SD) using solvent evaporation method were fabricated for the drug with different drug to polymer weight ratios of 1:1, 1:2 and 1:3. SD and physical mixture were characterized through in vitro dissolution, infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. The best enteric SD and SD using β-CD was tested in vivo for their ulcerogenic activity. Sulindac was highly dispersed inside CAP system that efficiently limited its release inside the stomach while no occurrence of any physicochemical interactions with the drug. β-CD improved the drug aqueous solubility, however it couldn’t protect against gastric ulcers induced by sulindac. SD using CAP as enteric polymer at a ratio of 1:2 significantly suppressed gastric ulceration. Direct exposure of sulindac to the stomach wall had the major contribution to its ulcerogenic activity rather than its poor gastric solubility. The gastrointestinal intolerance of sulindac could be addressed by avoiding its acute local contact with the ulcer-prone areas.