Co-processing of nateglinide with meglumine for enhanced dissolution rate: in vitro and in vivo evaluation
| Autor: | Ebtessam A. Essa, Gamal M. El Maghraby, Ahmed Nouh, Alaa Y. Bazeed |
|---|---|
| Přispěvatelé: | Bazeed, Alaa Y., Essa, Ebtessam A, Nouh, Ahmed, El Maghraby, Gamal M |
| Rok vydání: | 2020 |
| Předmět: |
Pharmacology
Meglumine salt formation Chemistry Organic Chemistry Pharmaceutical Science Nateglinide 02 engineering and technology 021001 nanoscience & nanotechnology 030226 pharmacology & pharmacy hypoglycemic effect In vitro 03 medical and health sciences 0302 clinical medicine In vivo Drug Discovery medicine dissolution rate meglumine 0210 nano-technology Enhanced dissolution Salt formation medicine.drug Nuclear chemistry |
| Zdroj: | Drug Development and Industrial Pharmacy. 46:1676-1683 |
| ISSN: | 1520-5762 0363-9045 |
| DOI: | 10.1080/03639045.2020.1820035 |
| Popis: | Refereed/Peer-reviewed Objective: The aim of this work was to investigate dry co-grinding of nateglinide with meglumine for enhanced dissolution rate of nateglinide. The study was extended to investigate the effect of this dissolution enhancement on the hypoglycemic effect of the drug in diabetic rats. Methods: Nateglinide was subjected to dry co-grinding with increasing proportions of meglumine to prepare products containing the drug with meglumine at 1:1, 1:2, and 1:3 molar ratios. These products were evaluated using combined instrumental analysis which employed Fourier transform infrared spectroscopy (FTIR), differential thermal analysis (DTA), and X-ray diffraction (XRD). Drug dissolution was also monitored before and after processing with and without meglumine. The optimum ratio was used to assess the effect of dissolution enhancement on the hypoglycemic effect of nateglinide on diabetic rats. The unprocessed nateglinide was used as control. Results: Co-grinding of nateglinide resulted in changes in the FTIR spectral patterns of nateglinide and meglumine. The changes suggested the formation of amide bond between both compounds at 1:1 molar ratio. The new species was confirmed by DTA and XRD. This species exhibited fast dissolution of nateglinide after incorporation of higher proportions of meglumine. Co-grinding was essential as indicated from slower dissolution from physical mixture containing the highest proportion of meglumine. Enhanced dissolution was reflected in vivo as improved rate and extent of hypoglycemia. Conclusion: Dry co-grinding of nateglinide with meglumine developed new species which liberated nateglinide rapidly and enhanced the rate and extent of hypoglycemia of nateglinide. usc |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |