Co-crystal is believed to improve the solubility and<br> dissolution rates and thus, enhanc... more Co-crystal is believed to improve the solubility and<br> dissolution rates and thus, enhanced the bioavailability of poor water<br> soluble drugs particularly during the oral route of administration.<br> With the existing of poorly soluble drugs in pharmaceutical industry,<br> the screening of co-crystal formation using carbamazepine (CBZ) as<br> a model drug compound with dicarboxylic acids co-crystal formers<br> (CCF) namely fumaric (FA) and succinic (SA) acids in ethanol has<br> been studied. The co-crystal formations were studied by varying the<br> mol ratio values of CCF to CBZ to access the effect of CCF<br> concentration on the formation of the co-crystal. Solvent evaporation,<br> slurry and cooling crystallization which representing the solution<br> based method co-crystal screening were used. Based on the<br> differential scanning calorimetry (DSC) analysis, the melting point of<br> CBZ-SA in diff...
The study aimed to determine the solubility of carbamazepine (CBZ) co-crystals formed from co-cry... more The study aimed to determine the solubility of carbamazepine (CBZ) co-crystals formed from co-crystal formers (CCFs) of nicotinamide (NIC), saccharin (SAC), succinic acid (SUC) and fumaric acid (FUM) at various temperatures (25-50°C). High Performance Liquid Chromatography (HPLC) was used to determine the solubility and the X-Ray Powder Diffraction was used to characterize the crystals. The solubility of CBZ-NIC and CBZ-FUM co-crystals were found to be higher than the solubility of the CBZ for the range of studied temperatures. However, opposite findings was obtained for CBZ-SUC co-crystal as its solubility is lower than the solubility of CBZ. Different trend was found for CBZ-SAC co-crystal in which for temperature lower than 40°C, the solubility of CBZ crystal is higher than the CBZSAC co-crystal. The solubility of CBZ-SAC co-crystal is higher than the solubility of CBZ at a temperature above 40°C. CBZ co-crystals with NIC and FUM have shown to increase the solubility of CBZ by solubility ratio of 1.95 and 1.24 respectively. However, the CBZ co-crystal with SAC was found to have similar solubility value as the CBZ.
Co-crystals is a multi-component system which connected by non-covalent interactions, present phy... more Co-crystals is a multi-component system which connected by non-covalent interactions, present physically as a solid form under ambient conditions. Nowadays, co-crystal has becoming as an alternative approach to improve the bioavailability of poor water soluble drugs especially for a weakly ionisable groups or neutral compounds. In this study the co-crystal screening was carried out for carbamazepine (CBZ) and fumaric acid (FUM) co-crystal former (CCF) using non-stoichiometric method (addition of CBZ to CCF saturated solution) and stoichiometric method (evaporation of 1:1 molar ratio of CBZ to CCF) in acetonitrile, ethyl acetate, propanol, ethanol and formic acid solvent systems. The crystals produced from the screening were characterized using Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared (FT-IR). The PXRD analysis had confirmed that the co-crystal was successfully formed in both methods for all of the solvent system studied with an exception to formic acid in the stoichiometric method where no crystal was found precipitate. The findings from this study revealed that Form A and Form B of CBZ-FUM co-crystal had been successfully formed from different solvent systems.
Solubility of carbamazepine co-crystal produced from cooling co-crystallization process with succ... more Solubility of carbamazepine co-crystal produced from cooling co-crystallization process with succinic acid as a co-crystal former is investigated in this study. Two techniques were used to determine the solubility of the co-crystal which are gravimetry and HPLC. The solubility experiments in ethanol solvent systems were conducted at 6 different temperatures (25, 30, 35, 40, 45 and 50 °C) while for succinic acid ethanolic solution system were conducted at 5 different concentration ratios. Both of the systems are equilibrated for 72 hours. Result from the experiments has shown that the solubility of co-crystal is temperature dependent. As the temperature increases, the solubility of co-crystal also increases; this agrees with the Second Law of Thermodynamic which states that heat facilitates the dissolution process by providing more energy to the system.
International Journal of Chemical Engineering and Applications, 2017
Co-crystal plays a critical role in the pharmaceutical industry and becoming as an alternative ap... more Co-crystal plays a critical role in the pharmaceutical industry and becoming as an alternative approach to improve the bioavailability of poor water soluble drugs especially for a weakly ionisable groups or neutral compounds. In this study the co-crystal screening was carried out for carbamazepine (CBZ) and co-crystal former (CCF) of fumaric acid (FUM) and succinic acid (SA) using non-stoichiometric method (addition of CBZ to CCF saturated solution) and stoichiometric method (evaporation of 1:1 molar ratio of CBZ to CCF) in acetonitrile, ethyl acetate, propanol, ethanol and formic acid solvent systems. The crystals produced from the screening were characterized using Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared (FT-IR). The PXRD analysis had confirmed that the co-crystal was successfully formed in both methods for all of the solvent system studied with an exception to formic acid in the stoichiometric method for CBZ-FUM system and in all methods for CBZ-SA system. The findings from this analysis revealed that Form A and Form B of CBZ-FUM co-crystal had been successfully formed from different solvents systems. DSC analysis had shown that the melting point of CBZ-FUM and CBZ-SA co-crystals were in the range similar to the previous study. The characterization using FT-IR indicated that the functional groups which include amides and carboxylic acids were presented in the co-crystal produced. Further study on the co-crystal solubility and dissolution rate is needed in order to access the efficacy of the co-crystal since the screening methods have been successfully confirmed the formation of the co-crystal.
Co-crystal is believed to improve the solubility and<br> dissolution rates and thus, enhanc... more Co-crystal is believed to improve the solubility and<br> dissolution rates and thus, enhanced the bioavailability of poor water<br> soluble drugs particularly during the oral route of administration.<br> With the existing of poorly soluble drugs in pharmaceutical industry,<br> the screening of co-crystal formation using carbamazepine (CBZ) as<br> a model drug compound with dicarboxylic acids co-crystal formers<br> (CCF) namely fumaric (FA) and succinic (SA) acids in ethanol has<br> been studied. The co-crystal formations were studied by varying the<br> mol ratio values of CCF to CBZ to access the effect of CCF<br> concentration on the formation of the co-crystal. Solvent evaporation,<br> slurry and cooling crystallization which representing the solution<br> based method co-crystal screening were used. Based on the<br> differential scanning calorimetry (DSC) analysis, the melting point of<br> CBZ-SA in diff...
The study aimed to determine the solubility of carbamazepine (CBZ) co-crystals formed from co-cry... more The study aimed to determine the solubility of carbamazepine (CBZ) co-crystals formed from co-crystal formers (CCFs) of nicotinamide (NIC), saccharin (SAC), succinic acid (SUC) and fumaric acid (FUM) at various temperatures (25-50°C). High Performance Liquid Chromatography (HPLC) was used to determine the solubility and the X-Ray Powder Diffraction was used to characterize the crystals. The solubility of CBZ-NIC and CBZ-FUM co-crystals were found to be higher than the solubility of the CBZ for the range of studied temperatures. However, opposite findings was obtained for CBZ-SUC co-crystal as its solubility is lower than the solubility of CBZ. Different trend was found for CBZ-SAC co-crystal in which for temperature lower than 40°C, the solubility of CBZ crystal is higher than the CBZSAC co-crystal. The solubility of CBZ-SAC co-crystal is higher than the solubility of CBZ at a temperature above 40°C. CBZ co-crystals with NIC and FUM have shown to increase the solubility of CBZ by solubility ratio of 1.95 and 1.24 respectively. However, the CBZ co-crystal with SAC was found to have similar solubility value as the CBZ.
Co-crystals is a multi-component system which connected by non-covalent interactions, present phy... more Co-crystals is a multi-component system which connected by non-covalent interactions, present physically as a solid form under ambient conditions. Nowadays, co-crystal has becoming as an alternative approach to improve the bioavailability of poor water soluble drugs especially for a weakly ionisable groups or neutral compounds. In this study the co-crystal screening was carried out for carbamazepine (CBZ) and fumaric acid (FUM) co-crystal former (CCF) using non-stoichiometric method (addition of CBZ to CCF saturated solution) and stoichiometric method (evaporation of 1:1 molar ratio of CBZ to CCF) in acetonitrile, ethyl acetate, propanol, ethanol and formic acid solvent systems. The crystals produced from the screening were characterized using Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared (FT-IR). The PXRD analysis had confirmed that the co-crystal was successfully formed in both methods for all of the solvent system studied with an exception to formic acid in the stoichiometric method where no crystal was found precipitate. The findings from this study revealed that Form A and Form B of CBZ-FUM co-crystal had been successfully formed from different solvent systems.
Solubility of carbamazepine co-crystal produced from cooling co-crystallization process with succ... more Solubility of carbamazepine co-crystal produced from cooling co-crystallization process with succinic acid as a co-crystal former is investigated in this study. Two techniques were used to determine the solubility of the co-crystal which are gravimetry and HPLC. The solubility experiments in ethanol solvent systems were conducted at 6 different temperatures (25, 30, 35, 40, 45 and 50 °C) while for succinic acid ethanolic solution system were conducted at 5 different concentration ratios. Both of the systems are equilibrated for 72 hours. Result from the experiments has shown that the solubility of co-crystal is temperature dependent. As the temperature increases, the solubility of co-crystal also increases; this agrees with the Second Law of Thermodynamic which states that heat facilitates the dissolution process by providing more energy to the system.
International Journal of Chemical Engineering and Applications, 2017
Co-crystal plays a critical role in the pharmaceutical industry and becoming as an alternative ap... more Co-crystal plays a critical role in the pharmaceutical industry and becoming as an alternative approach to improve the bioavailability of poor water soluble drugs especially for a weakly ionisable groups or neutral compounds. In this study the co-crystal screening was carried out for carbamazepine (CBZ) and co-crystal former (CCF) of fumaric acid (FUM) and succinic acid (SA) using non-stoichiometric method (addition of CBZ to CCF saturated solution) and stoichiometric method (evaporation of 1:1 molar ratio of CBZ to CCF) in acetonitrile, ethyl acetate, propanol, ethanol and formic acid solvent systems. The crystals produced from the screening were characterized using Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared (FT-IR). The PXRD analysis had confirmed that the co-crystal was successfully formed in both methods for all of the solvent system studied with an exception to formic acid in the stoichiometric method for CBZ-FUM system and in all methods for CBZ-SA system. The findings from this analysis revealed that Form A and Form B of CBZ-FUM co-crystal had been successfully formed from different solvents systems. DSC analysis had shown that the melting point of CBZ-FUM and CBZ-SA co-crystals were in the range similar to the previous study. The characterization using FT-IR indicated that the functional groups which include amides and carboxylic acids were presented in the co-crystal produced. Further study on the co-crystal solubility and dissolution rate is needed in order to access the efficacy of the co-crystal since the screening methods have been successfully confirmed the formation of the co-crystal.
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