Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and in vivo Profile
Fahad Mehmood Khan,1 Mahmood Ahmad,2 Hafiz Arfat Idrees1 1Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Punjab 63100, Pakistan; 2Faculty of Pharmacy, University of Central Punjab, Punjab 54000, PakistanCorrespondence: Mahmood Ahmad Tel +92 300 9682258Email ma786...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2020-10-01
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| Series: | Drug Design, Development and Therapy |
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| Online Access: | https://test.dovepress.com/simvastatin-nicotinamide-co-crystals-formation-pharmaceutical-characte-peer-reviewed-article-DDDT |
| _version_ | 1819232183977508864 |
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| author | Khan FM Ahmad M Idrees HA |
| author_facet | Khan FM Ahmad M Idrees HA |
| author_sort | Khan FM |
| collection | DOAJ |
| description | Fahad Mehmood Khan,1 Mahmood Ahmad,2 Hafiz Arfat Idrees1 1Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Punjab 63100, Pakistan; 2Faculty of Pharmacy, University of Central Punjab, Punjab 54000, PakistanCorrespondence: Mahmood Ahmad Tel +92 300 9682258Email ma786_786@yahoo.comPurpose: To enhance the solubility and dissolution profile of simvastatin (SIM) through co-crystallization with varying ratios of nicotinamide (NIC) using various co-methods.Materials and Methods: Twelve SIM:NIC co-crystal formulations (F01–F12) were prepared using dry grinding, slurry, liquid-assisted grinding, and solvent-evaporation methods, and their properties compared. Optimized formulations were selected on the basis of dissolution profiles and solubility for in vivo studies. The angle of repose, Carr Index and Hausner ratio were calculated to evaluate flow properties. Differential light scattering (DLS) was used to estimate particle-size distribution. Scanning electron microscopy (SEM) was employed to evaluate surface morphology. Thermal analyses and Fourier-transform infrared (FTIR) spectroscopy were used to determine the ranges of thermal stability and physical interaction of formulated co-crystals. X-ray powder diffraction (XPD) spectroscopy was used to determine the crystalline nature. Solubility and dissolution studies were undertaken to determine in vitro drug-release behaviors.Results: Micromeritic analyses revealed the good flow properties of formulated co-crystals. DLS showed the particle size of co-crystals to be in the nanometer range. SEM revealed that the co-crystals were regular cubes. Thermal studies showed the stability of co-crystals at > 300°C. FTIR spectroscopy revealed minor shifts of various peaks. XPD spectroscopy demonstrated co-crystal formation. The formulations exhibited an improved dissolution profile with marked improvements in solubility. In vivo studies showed a 2.4-fold increase in Cmax whereas total AUC(0–∞) was increased 4.75-fold as compared with that of SIM tablets.Conclusion: Co-crystallization with NIC improved the solubility and dissolution profile and, hence, the bioavailability of the poorly water-soluble drug SIM.Keywords: pharmacokinetics, solubility enhancement, simvastatin, nicotinamide, co-crystal |
| first_indexed | 2024-12-23T11:56:49Z |
| format | Article |
| id | doaj.art-7436fe025fe84831a717eb055ce7bc1e |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-23T11:56:49Z |
| publishDate | 2020-10-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-7436fe025fe84831a717eb055ce7bc1e2022-12-21T17:48:03ZengDove Medical PressDrug Design, Development and Therapy1177-88812020-10-01Volume 144303431358231Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and in vivo ProfileKhan FMAhmad MIdrees HAFahad Mehmood Khan,1 Mahmood Ahmad,2 Hafiz Arfat Idrees1 1Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Punjab 63100, Pakistan; 2Faculty of Pharmacy, University of Central Punjab, Punjab 54000, PakistanCorrespondence: Mahmood Ahmad Tel +92 300 9682258Email ma786_786@yahoo.comPurpose: To enhance the solubility and dissolution profile of simvastatin (SIM) through co-crystallization with varying ratios of nicotinamide (NIC) using various co-methods.Materials and Methods: Twelve SIM:NIC co-crystal formulations (F01–F12) were prepared using dry grinding, slurry, liquid-assisted grinding, and solvent-evaporation methods, and their properties compared. Optimized formulations were selected on the basis of dissolution profiles and solubility for in vivo studies. The angle of repose, Carr Index and Hausner ratio were calculated to evaluate flow properties. Differential light scattering (DLS) was used to estimate particle-size distribution. Scanning electron microscopy (SEM) was employed to evaluate surface morphology. Thermal analyses and Fourier-transform infrared (FTIR) spectroscopy were used to determine the ranges of thermal stability and physical interaction of formulated co-crystals. X-ray powder diffraction (XPD) spectroscopy was used to determine the crystalline nature. Solubility and dissolution studies were undertaken to determine in vitro drug-release behaviors.Results: Micromeritic analyses revealed the good flow properties of formulated co-crystals. DLS showed the particle size of co-crystals to be in the nanometer range. SEM revealed that the co-crystals were regular cubes. Thermal studies showed the stability of co-crystals at > 300°C. FTIR spectroscopy revealed minor shifts of various peaks. XPD spectroscopy demonstrated co-crystal formation. The formulations exhibited an improved dissolution profile with marked improvements in solubility. In vivo studies showed a 2.4-fold increase in Cmax whereas total AUC(0–∞) was increased 4.75-fold as compared with that of SIM tablets.Conclusion: Co-crystallization with NIC improved the solubility and dissolution profile and, hence, the bioavailability of the poorly water-soluble drug SIM.Keywords: pharmacokinetics, solubility enhancement, simvastatin, nicotinamide, co-crystalhttps://test.dovepress.com/simvastatin-nicotinamide-co-crystals-formation-pharmaceutical-characte-peer-reviewed-article-DDDTpharmacokineticssolubility enhancementsimvastatinnicotinamideco-crystal |
| spellingShingle | Khan FM Ahmad M Idrees HA Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and in vivo Profile Drug Design, Development and Therapy pharmacokinetics solubility enhancement simvastatin nicotinamide co-crystal |
| title | Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and in vivo Profile |
| title_full | Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and in vivo Profile |
| title_fullStr | Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and in vivo Profile |
| title_full_unstemmed | Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and in vivo Profile |
| title_short | Simvastatin-Nicotinamide Co-Crystals: Formation, Pharmaceutical Characterization and in vivo Profile |
| title_sort | simvastatin nicotinamide co crystals formation pharmaceutical characterization and in vivo profile |
| topic | pharmacokinetics solubility enhancement simvastatin nicotinamide co-crystal |
| url | https://test.dovepress.com/simvastatin-nicotinamide-co-crystals-formation-pharmaceutical-characte-peer-reviewed-article-DDDT |
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