Abstract
Objective: The aim of this study was to develop a solid dosage form of glibenclamide with increasing the solubility properties of glibenclamide with cocrystallization method.Methods: Virtual screening was performed to investigate the interaction between glibenclamide and a co-former. Saccharin, the selected co-former, then co-crystallized with glibenclamide with equimolar ratios of 1:1 and 1:2 using the solvent evaporation method. Further characterization was performed using an infra-red (IR) spectrophotometer, differential scanning calorimetry (DSC), and powder x-ray diffraction (PXRD).Results: Co-crystals of 1:2 equimolar ratio were more highly soluble compared to pure glibenclamide (30-fold for 12 h and 24-fold for 24 h). The dissolution rate had also increased from 46.838% of pure glibenclamide to 77.655% of glibenclamide co-crystal in 60 min. There was no chemical reaction observed during the co-crystallization process based on the IR spectrum. However, there was a new peak in the X-Ray diffractogram and a reduction of melting point in the DSC curve, indicating the formation of co-crystals.Conclusion: The optimal co-crystal ratio of glibenclamide-saccharin was found to be 1:2, which was successful in improving the solubility of glibenclamide.
Highlights
Oral preparation is the easiest and most widely used drug delivery route because it has several advantages, namely ease of administration, high level of patient compliance, cost-effective, and tends to be flexible in terms of dosage formulations
Molecular docking was used to determine that the selected parameter of the co-former had a high number of hydrogen bonds and a small value of energy of interaction (Ei); the smaller the Ei, the stronger the bond [20]
Hydrogen bonds were formed from hydrogen atoms of the amide groups of glibenclamide and oxygen atoms of sulfonyl of saccharin
Summary
Oral preparation is the easiest and most widely used drug delivery route because it has several advantages, namely ease of administration, high level of patient compliance, cost-effective, and tends to be flexible in terms of dosage formulations. The biggest challenge in designing oral dosage form is low bioavailability property. Bioavailability is influenced by several factors, including water solubility, drug permeability, dissolution rate, first-pass metabolism, and pre-systemic metabolism. The most common causes of low bioavailability are low solubility and permeability [1, 2]. Nearly 40% of pharmaceutical preparations on the market have low solubility based on the biopharmaceutical classification system (BCS). The industry consensus thought that those candidates was highly risk in drug development. Because of the large number of them, the industry consensus changed the point of view of the drugs from avoidance to acceptance as the dedication of the research provided to solve the challenges regarding the solubility [4, 5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
