Studies on Cocrystal Formation of Metaxalone with Short-chain Dicarboxylic Acids

A possible cocrystal formation between metaxalone and short-chain dicarboxylic acids (HOOC-(CH2)n-COOH, n=0-3) was quickly investigated using a solvent-assisted grinding approach. Differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) microspectroscopy, and powder X-ray diffraction (PXRD) were used to verify the cocrystal formation between metaxalone and each dicarboxylic acid. A solvent evaporation method was used to prepare the standard cocrystal. The cocrystal formation was also estimated by using a one-step simultaneous DSC-FTIR microspectroscopy. The present study indicates that only n=2 of short-chain dicarboxylic acids such as succinic acid, fumaric acid and maleic acid could form a cocrystal with metaxalone. Both solvent-assisted grinding technique and solvent evaporation method were successfully applied to prepare the metaxalone cocrystal with n=2 of short-chain dicarboxylic acids. Moreover, this cocrystal formation was also easily screened and estimated using a unique DSC-FTIR microspectroscopy in real time. Acknowledgement This work was supported by National Science Council, Taipei, Taiwan, ROC (NSC 100-2320-B- 264-001-MY3).

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Glibenclamide-Nicotinamide Cocrystals Synthesized by The Solvent Evaporation Method to Enhance Solubility and Dissolution Rate of Glibenclamide

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.9.1.4 ◽

2019 ◽

Vol 9 (01) ◽

pp. 21-26

Author(s):

Arif Budiman ◽

Ayu Apriliani ◽

Tazyinul Qoriah ◽

Sandra Megantara

Keyword(s):

Solvent Evaporation ◽

Physical Mixture ◽

Dissolution Profile ◽

Solvent Evaporation Method ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Evaporation Method ◽

Dissolution Properties ◽

Mixture Characterization

Purpose: To develop glibenclamide-nicotinamide cocrystals with the solvent evaporation method and evaluate their solubility and dissolution properties. Methods: Cocrystals of glibenclamide-nicotinamide (1:2) were prepared with the solvent evaporation method. The prediction of interactive cocrystals was observed using in silico method. The solubility and dissolution were performed as evaluation of cocrystals. The cocrystals also were characterized by differential scanning calorimetry (DSC), infrared spectrophotometry, and powder X-ray diffraction (PXRD). Result: The solubility and dissolution profile of glibenclamide-nicotinamide cocrystal (1:2) increased significantly compared to pure glibenclamide as well as its physical mixture. Characterization of cocrystal glibenclamide-nicotinamide (1:2) including infrared Fourier transform, DSC, and PXRD, indicated the formation of a new solid crystal phase differing from glibenclamide and nicotinamide. Conclusion: The confirmation of cocrystal glibenclamide-nicotinamide (1:2) indicated the formation of new solid crystalline phases that differ from pure glibenclamide and its physical mixture

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COMPLEX OF ELUXADOLINE WITH SODIUM CAPRYLATE FOR IMPROVED SOLUBILITY AND DISSOLUTION RATE

INDIAN DRUGS ◽

10.53879/id.57.11.11857 ◽

2021 ◽

Vol 57 (11) ◽

pp. 22-26

Author(s):

Manisha Dhere ◽

◽

Arti Majumdar ◽

Neelesh Malviya

Keyword(s):

Dissolution Rate ◽

Solvent Evaporation ◽

Drug Dissolution ◽

Dissolution Enhancement ◽

Solvent Evaporation Method ◽

Scanning Calorimetry ◽

Evaporation Method ◽

Solubility Study ◽

Sodium Caprylate

In the present research, newly developed complex with sodium caprylate was investigated for solubility and dissolution enhancement of eluxadoline. Complexes were prepared in different ratios by solvent evaporation method and characterised solubility study, Infrared spectroscopy (IR), Diffrential scanning calorimetry (DSC), X-Ray Diffraction (XRD), drug content analysis and in vitro Drug release. The solubility and dissolution rate revealed most suitable ratio of eluxadoline and sodium caprylate (1:4). The IR, DSC and X-RD data also confirmed the results. It was concluded that complex prepared with (1:4 drug:sodium caprylate ratio) using solvent evaporation method showed significant improvement in solubility and drug dissolution.

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Co-crystallization of quercetin and isonicotinamide using solvent evaporation method

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i4.3 ◽

2021 ◽

Vol 18 (4) ◽

pp. 697-702

Author(s):

Budipratiwi Wisudyaningsih ◽

Dwi Setyawan ◽

Siswandono

Keyword(s):

Minimum Energy ◽

Solvent Evaporation ◽

Crystal Habit ◽

In Vitro Dissolution ◽

Molar Ratio ◽

Dissolution Profile ◽

Solvent Evaporation Method ◽

Scanning Calorimetry ◽

Evaporation Method

Purpose: To obtain quercetin-isonicotinamide co-crystal (CQINA) with improved physicochemical and in-vitro dissolution characteristics. Methods: Co-crystallization of quercetin (Q) and isonicotinamide (INA) in molar ratio of 1:1 was performed using solvent evaporation method with the addition of 50 mL of ethanol (99.9%, v/v). The resultant solution was thoroughly mixed and stirred at room temperature for 48 h to slowly evaporate the solvent until CQINA was obtained. The co-crystal phase was characterized using differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), scanning electron microscopy (SEM), and fourier transform infrared (FTIR) spectroscopy. In-vitro dissolution was performed by USP method II in 900 mL citrate buffer (pH 5.0 ± 0.05), with stirring at 100 rpm and at 37 ± 0.5 °C. Results: Computational approach predicted the formation of hydrogen bonds between Q and coformers used, and the interaction involved minimum energy. In CQINA thermogram, a new endothermic peak was formed with a melting point of 255.26 °C, while Q (314.85 °C) and INA (156.62 °C). Images from DSC, PXRD, SEM and FTIR showed that the crystal habits and morphologies of the CQINA differed from those of the original components. There was an improvement in the dissolution profile of CQINA, when compared with those of the original components. Conclusion: Q and INA subjected to solvent evaporation result in the formation of a CQINA with different crystal habit, which possess physicochemical characteristics different from those of its constituents. Modification of Q crystals in CQINA increases its in vitro dissolution, making it a potential pharmaceutical agent.

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Identification of Physical Interaction in Binary Systems of Acyclovir – Succinic Acid

JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA ◽

10.20473/jfiki.v3i12016.27-31 ◽

2017 ◽

Vol 3 (1) ◽

pp. 27

Author(s):

Agnes Nuniek Winanta ◽

Dwi Setyawan ◽

Siswandono

Keyword(s):

Succinic Acid ◽

Binary Systems ◽

Antiviral Drug ◽

Solvent Evaporation ◽

Crystal Habit ◽

Physical Interaction ◽

Solvent Evaporation Method ◽

Scanning Calorimetry ◽

Pxrd Pattern ◽

Evaporation Method

Background: Acyclovir, a guanosine analogue antiviral drug with low solubility of water. Due to its poor solubility and permeability, causes low oral bioavailability. Objective: The aim of this research is to investigate the physical interaction in binary systems acyclovir-succinic acid (AS). Methods: The msystem was prepared by solvent evaporation method. Results: Thermogram Differential Scanning Calorimetry showed endothermic peaks at 172.68oC (ethanol) and 171.84oC (methanol). The Powder X-Ray Diffraction (PXRD) pattern of AS was different from pure component and physical mixtures. Furthermore, physical characterization showed the binary system of AS have unique crystal habit by polarization microscope. Conclusion: New crystalline phase is formed from the interaction between acyclovir and succinic acid by solvent evaporation method using ethanol and methanol.

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Multi-Component Crystals of 2,2′-Bipyridine with Aliphatic Dicarboxylic Acids: Melting Point-Structure Relations

Crystals ◽

10.3390/cryst11101151 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1151

Author(s):

Vhukhudo Nethanani ◽

Eustina Batisai

Keyword(s):

Melting Point ◽

Dicarboxylic Acids ◽

Conformation Analysis ◽

Solvent Evaporation Method ◽

X Ray Diffraction ◽

Melting Points ◽

Scanning Calorimetry ◽

X Ray ◽

Aliphatic Dicarboxylic Acids ◽

The Relationship

The aim of the study was to investigate the relationship between the melting point and the supramolecular structure of three multi-component crystals of aliphatic dicarboxylic acids with 2,2′-bipyridine and to investigate the conformations of 2,2′-bipyridine in published multi-component crystals. The crystals were prepared using the solvent evaporation method and were characterized using single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). The crystal structures were further analyzed using CrystalExplorer, and the results were correlated with the melting points. The results of the conformation analysis of the reported multi-component crystals of 2,2′-bipyridine are also presented.

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Identification of Physical Interaction in Binary Systems of Acyclovir – Succinic Acid

JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA ◽

10.20473/jfiki.v3i1.4091 ◽

2017 ◽

Vol 3 (1) ◽

pp. 27

Author(s):

Agnes Nuniek Winanta ◽

Dwi Setyawan ◽

Siswandono

Keyword(s):

Succinic Acid ◽

Binary Systems ◽

Antiviral Drug ◽

Solvent Evaporation ◽

Crystal Habit ◽

Physical Interaction ◽

Solvent Evaporation Method ◽

Scanning Calorimetry ◽

Pxrd Pattern ◽

Evaporation Method

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SOLID DOSAGE FORM DEVELOPMENT OF GLIBENCLAMIDE-ASPARTAME COCRYSTAL USING THE SOLVENT EVAPORATION METHOD TO INCREASE THE SOLUBILITY OF GLIBENCLAMIDE

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019v11i3.32121 ◽

2019 ◽

pp. 150-154

Author(s):

ARIF BUDIMAN ◽

SANDRA MEGANTARA ◽

AYU APRILIANI

Keyword(s):

Hydrogen Bonding ◽

Dissolution Rate ◽

In Silico ◽

Active Pharmaceutical Ingredient ◽

Solvent Evaporation ◽

Solvent Evaporation Method ◽

Scanning Calorimetry ◽

Evaporation Method ◽

Rate Test ◽

Ft Ir

Objective: The solubility of a drug in water plays an important role in the absorption of the drug after oral administration. Cocrystal is one method that improves the solubility of the active pharmaceutical ingredient (API). The aim of this study was to investigate the formation of a glibenclamide (GCM)-aspartame (APM) cocrystal using the solvent evaporation method and to evaluate its solubility and dissolution rate. Methods: Molecular docking of the GCM-APM cocrystal was observed using an in silico method. The GCM-APM cocrystal (1:2) was prepared by using the solvent evaporation method. The cocrystal of GCM-APM was evaluated by the saturated solubility test and the dissolution rate test (USP type 2 apparatus). The solvent evaporation product of GCM-APM was characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD). Results: In silico study showed that the interaction of GCM-APM has hydrogen bonding and the potential to improve the solubility of GCM. Evaluation of the cocrystal of GCM-APM showed that the solubility and dissolution rate of the cocrystal are significantly increased. Characterization of FT-IR showed that no chemical reaction occurred in the GCM-APM cocrystal. The DSC analysis showed the changes in the melting point of GCM. Measurement of PXRD showed the formation of a new solid crystal phase that is different from GCM and APM. Conclusion: GCM-APM has hydrogen bonding can improve the solubility and dissolution rate of GCM.

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Facile Preparation of Polylactic Acid/Ketoconazole Composite Microspheres by Oil/Water Solvent Evaporation Method

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.652-654.335 ◽

2013 ◽

Vol 652-654 ◽

pp. 335-338 ◽

Cited By ~ 3

Author(s):

Yan Hong Zhang ◽

Yan Wang ◽

Xian Chao Kong ◽

Qian Ke Cheng ◽

Xi Yuan Yang ◽

...

Keyword(s):

Polylactic Acid ◽

Solvent Evaporation ◽

Thermal Decomposition Mechanism ◽

Solvent Evaporation Method ◽

X Ray Diffraction ◽

Evaporation Method ◽

Composite Microspheres ◽

Water Solvent ◽

Ft Ir ◽

Oil Water

In this study, polylactic acid(PLA)/ketoconazole(KCZ) composite microspheres were prepared by oil/water solvent evaporation method. Those drug-loaded microspheres were characterized in morphology using the scanning electron microscope (SEM). Fourier transform infrared spectroscopy (FT-IR) was used to determine the chemical functional groups in the sample and to analysis whether a chemical reaction occured between PLA and KCZ. The thermogravimetric spectra of PLA and PLA/KCZ microspheres were used to analyse the influence of KCZ on the thermal decomposition mechanism of PLA. Crystallinities of the KCZ and PLA/KCZ were analyzed by X-ray diffraction analysis (XRD).

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Preparation and Evaluation of Glipizide Tablets Containing both Enhanced and Sustained Release Solid Dispersions

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2009.2.4.5 ◽

1970 ◽

Vol 2 (4) ◽

pp. 714-725

Author(s):

Adel M. Aly ◽

Ahmed S. Ali

Keyword(s):

Blood Glucose ◽

Blood Glucose Level ◽

Glucose Level ◽

Solid Dispersions ◽

Solvent Evaporation ◽

In Vivo Studies ◽

Solvent Evaporation Method ◽

Evaporation Method ◽

Tablet Formulations

: Glipizide (GZ) is an oral blood-glucose-lowering drug of the sulfonylurea class characterized by its poor aqueous solubility. Aiming for the production of GZ tablets with rapid onset of action followed by prolonged effect; GZ-Polyethylene glycol (PEG 4000 and 6000) solid dispersions with different ratios, (using melting and solvent evaporation method), as well as, coprecipitate containing GZ with polymethyl-methacrylate (PMMA) were prepared. Four tablet formulations were prepared containing; a) GZ alone, b) GZ: PEG6000, 1:10, c) GZ:PMMA 1:3, and, d)both GZ:PEG6000 1:10 and GZ:PMMA 1:3. The solvent evaporation method showed more enhancement of GZ solubility than the melting one, and this solubilizing effect increased with PEG increment. Generally, PEG6000 showed more enhancement of dissolution than PEG4000 especially at 1:10 drug: polymer ratio (the most enhancing formula). Also, the prepared tablet formulations showed acceptable physical properties according to USP/NF requirements. The dissolution results revealed that tablets containing PEG6000 (1:10) have the most rapid release rate, followed by the formula containing both PEG6000 and PMMA, while that including PMMA alone showed the slowest dissolution rate. Moreover, In-vivo studies for each of the above four formulations, were performed using four mice groups. The most effective formula in decreasing the blood glucose level, through the first 6 hours, was that containing GZ and PEG6000, 1:10. However, formula containing the combination of enhanced and sustained GZ was the most effective in decreasing the blood glucose level through 16 hours. Successful in-vitro in-vivo correlations could be detected between the percent released and the percent decreasing of blood glucose level after 0.5 hours.

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Formulation Design and Optimization of Repaglinide Solid Dispersions by Central Composite Design

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2018.11.6.7 ◽

2018 ◽

Vol 11 (6) ◽

pp. 4337-4348

Author(s):

Bhikshapathi D. V. R. N. ◽

Srinivas I

Keyword(s):

Central Composite Design ◽

Dissolution Rate ◽

Solid Dispersion ◽

Solid Dispersions ◽

Solvent Evaporation ◽

Release Mechanism ◽

Solvent Evaporation Method ◽

Onset Of Action ◽

Evaporation Method ◽

Central Composite

Repaglinide is a pharmaceutical drug used for the treatment of type II diabetes mellitus, it is characterized with poor solubility which limits its absorption and dissolution rate and delays onset of action. In the present study, immediate release solid dispersion of repaglinide was formulated by solvent evaporation technique. Repaglinide solid dispersions were prepared using PEG 8000, Pluronic F 127 and Gelucire 44/14 by solvent evaporation method. A 3-factor, 3-level central composite design employed to study the effect of each independent variable on dependent variables. FTIR studies revealed that no drug excipient interaction takes place. From powder X-ray diffraction (p-XRD) and by scanning electron microscopy (SEM) studies it was evident that polymorphic form of repaglinide has been converted into an amorphous form from crystalline within the solid dispersion formulation. The correlation coefficient showed that the release profile followed Higuchi model anomalous behavior and hence release mechanism was indicative of diffusion. The obtained results suggested that developed solid dispersion by solvent evaporation method might be an efficacious approach for enhancing the solubility and dissolution rate of repaglinide.

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