scholarly journals Improving the Solubility of Aripiprazole by Multicomponent Crystallization

Crystals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 343
Author(s):  
Qi Zhou ◽  
Zhongchuan Tan ◽  
Desen Yang ◽  
Jiyuan Tu ◽  
Yezi Wang ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Weak Interactions ◽  
Theoretical Calculations ◽  
Water Soluble ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Intrinsic Dissolution ◽  
Intrinsic Dissolution Rate ◽  
X Ray ◽  
Water Soluble Drugs

Aripiprazole (ARI) is a third-generation antipsychotic with few side effects but a poor solubility. Salt formation, as one common form of multicomponent crystals, is an effective strategy to improve pharmacokinetic profiles. In this work, a new ARI salt with adipic acid (ADI) and its acetone hemisolvate were obtained successfully, along with a known ARI salt with salicylic acid (SAL). Their comprehensive characterizations were conducted using X-ray diffraction and differential scanning calorimetry. The crystal structures of the ARI-ADI salt acetone hemisolvate and ARI-SAL salt were elucidated by single-crystal X-ray diffraction for the first time, demonstrating the proton transfer from a carboxyl group of acid to ARI piperazine. Theoretical calculations were also performed on weak interactions. Moreover, comparative studies on pharmaceutical properties, including powder hygroscopicity, stability, solubility, and the intrinsic dissolution rate, were carried out. The results indicated that the solubility and intrinsic dissolution rate of the ARI-ADI salt and its acetone hemisolvate significantly improved, clearly outperforming that of the ARI-SAL salt and the untreated ARI. The study presented one potential alternative salt of aripiprazole and provided a potential strategy to increase the solubility of poorly water-soluble drugs.

scholarly journals Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 289
Author(s):  
Debora Zanolla ◽  
Dritan Hasa ◽  
Mihails Arhangelskis ◽  
Gabriela Schneider-Rauber ◽  
Michele R. Chierotti ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Polymorphic Form ◽  
In Vitro Tests ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Experimental Conditions ◽  
Intrinsic Dissolution ◽  
Intrinsic Dissolution Rate ◽  
X Ray ◽  
Enhanced Solubility

Praziquantel (PZQ) is the first-line drug used against schistosomiasis, one of the most common parasitic diseases in the world. A series of crystalline structures including two new polymorphs of the pure drug and a series of cocrystals of PZQ have been discovered and deposited in the Cambridge Structural Database (CSD). This work adds to the list of multicomponent forms of PZQ a relevant example of a racemic hemihydrate (PZQ-HH), obtainable from commercial PZQ (polymorphic Form A) through mechanochemistry. Noteworthy, the formation of the new hemihydrate strongly depends on the initial polymorphic form of PZQ and on the experimental conditions used. The new PZQ-HH has been fully characterized by means of HPLC, Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Hot-Stage Microscopy (SEM), Powder X-Ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), FT-IR, polarimetry, solid-state NMR (SS-NMR), solubility and intrinsic dissolution rate (IDR), and in vitro tests on Schistosoma mansoni adults. The crystal structure was solved from the powder X-ray diffraction pattern and validated by periodic-DFT calculations. The new bioactive hemihydrate was physically stable for three months and showed peculiar biopharmaceutical features including enhanced solubility and a double intrinsic dissolution rate in water in comparison to the commercially available PZQ Form A.

scholarly journals THE DEVELOPMENT OF GLIBENCLAMIDE-SACCHARIN COCRYSTAL TABLET FORMULATIONS TO INCREASE THE DISSOLUTION RATE OF THE DRUG

2019 ◽  
pp. 359-364 ◽  
Author(s):  
ARIF BUDIMAN ◽  
PATIHUL HUSNI ◽  
SHAFIRA ◽  
Tazyinul Q. Alfauziah
Keyword(s):  
Dissolution Rate ◽  
Dosage Form ◽  
Water Soluble ◽  
Crystal Habit ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Grinding Method ◽  
Water Soluble Drugs ◽  
Rate Test ◽  
Tablet Dosage

Objective: Cocrystallisation is a promising method in order to increase the solubility and dissolution of poorly water-soluble drugs. The aim of this study was to prepare, formulate and evaluate glibenclamide (GCM) cocrystal in direct compress tablet dosage form using saccharin (SAC) as the coformer. Methods: GCM cocrystal with various stoichiometric ratios were prepared by the solvent drop grinding method. The co-crystal was characterized by a saturated solubility test and dissolution rate test, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Powder X-Ray Diffraction (PXRD). The tablet dosage form of GCM was formulated and evaluated compare with the conventional dosage form. Results: The solubility and disso­lution rate of GCM-SAC cocrystals increased significantly compared with pure GCM, especially for 1:2 of ratio. The dissolution rate of cocrystal with ratio 1:2 increased by almost 91.9% compared with pure GCM. Based on the FTIR analysis, it showed the shifting of characteristic bands of GCM in the spectrum and there was no chemical reaction in GCM cocrystal. In PXRD measurement, the new crystalline peak was detected in the crystal habit of cocrystal compared with pure GCM and coformer. The new single melting of GCM-SAC cocrystal also was detected in DSC measurement. The tablets of GCM-SAC cocrystal were successfully prepared by direct compression method which rapidly disintegrated (1 min) and has higher dissolution compared with its pure form (32.36% greater than glibenclamide after 45 min). Conclusion: The tablet dosage form of GCM cocrystal with SAC as coformer was successfully prepared, formulated and improved its solubility and dissolution rate.

scholarly journals Coamorphous Atorvastatin Calcium to Improve its Physicochemical and Pharmacokinetic Properties

2013 ◽  
Vol 16 (4) ◽  
pp. 577 ◽  
Author(s):  
Ali Shayanfar ◽  
Hamed Ghavimi ◽  
Hamed Hamishekar ◽  
Abolghasem Jouyban
Keyword(s):  
Dissolution Rate ◽  
Plasma Concentrations ◽  
Solution Stability ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Intrinsic Dissolution ◽  
Intrinsic Dissolution Rate ◽  
Atorvastatin Calcium ◽  
Pharmacokinetic Properties ◽  
Improved Stability

Purpose: Atorvastatin calcium (ATC) is classified as class II (low solubility and high permeability) compound according to the biopharmaceutical classification system. The amorphous form of ATC possesses higher solubility, dissolution rate, and bioavailability than its crystalline form. Coamorphous drug system is a new and emerging method to prepare stable amorphous forms, in this case leading to the improved stability of ATC in dissolution medium. Methods: In this study, coamorphous form of ATC and nicotinamide (ATC-NIC) was  prepared from solvent evaporation method and characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and powder X-ray diffraction (PXRD). The intrinsic dissolution rate and solubility of ATC-NIC were determined along with plasma concentrations of ATC using HPLC after oral dosing in rats. Results: The crystalline ATC was converted to coamorphous form revealing a molecular interaction between ATC and NIC. The intrinsic dissolution rate, solubility and plasma concentration of coamorphous ATC-NIC are higher than those of crystalline ATC. ATC-NIC coamorphous system showed greater solution stability than those reported in the literature for amorphous ATC.   Conclusions: Coamorphous ATC-NIC has improved physicochemical and pharmacokinetic properties as compared to ATC. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Studies on the Preparation, Characterization and Solubility of -Cyclodextrin-Roxythromycin Inclusion Complexes

2009 ◽  
Vol 2 (2) ◽  
pp. 523-530
Author(s):  
D. Nagasamy Venkatesh ◽  
S. Karthick ◽  
M. Umesh ◽  
G. Vivek ◽  
R.M. Valliappan ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Inclusion Complexes ◽  
Phase Solubility ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Ir Studies ◽  
Poorly Soluble ◽  
Poorly Soluble Drug

Roxythromycin/ β-cyclodextrin (Roxy/ β-CD) dispersions were prepared with a view to study the influence of β-CD on the solubility and dissolution rate of this poorly soluble drug. Phase-solubility profile indicated that the solubility of roxythromycin was significantly increased in the presence of β-cyclodextrin and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Physical characterization of the prepared systems was carried out by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD) and IR studies. Solid state characterization of the drug β-CD binary system using XRD, FTIR and DSC revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement of dissolution rate.

Salts of purine alkaloids caffeine and theobromine with 2,6-dihydroxybenzoic acid as coformer: structural, theoretical, thermal and spectroscopic studies

2021 ◽  
Vol 77 (11) ◽  
Author(s):  
Mateusz Gołdyn ◽  
Anna Komasa ◽  
Mateusz Pawlaczyk ◽  
Aneta Lewandowska ◽  
Elżbieta Bartoszak-Adamska
Keyword(s):  
Hydrogen Bonds ◽  
Water Solubility ◽  
Theoretical Calculations ◽  
Spectroscopic Studies ◽  
X Ray Diffraction ◽  
Dihydroxybenzoic Acid ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Purine Alkaloids ◽  
Vis Spectroscopy

The study of various forms of pharmaceutical substances with specific physicochemical properties suitable for putting them on the market is one of the elements of research in the pharmaceutical industry. A large proportion of active pharmaceutical ingredients (APIs) occur in the salt form. The use of an acidic coformer with a given structure and a suitable pK a value towards purine alkaloids containing a basic imidazole N atom can lead to salt formation. In this work, 2,6-dihydroxybenzoic acid (26DHBA) was used for cocrystallization of theobromine (TBR) and caffeine (CAF). Two novel salts, namely, theobrominium 2,6-dihydroxybenzoate, C7H9N4O2 +·C7H5O4 − (I), and caffeinium 2,6-dihydroxybenzoate, C8H11N4O2 +·C7H5O4 − (II), were synthesized. Both salts were obtained independently by slow evaporation from solution, by neat grinding and also by microwave-assisted slurry cocrystallization. Powder X-ray diffraction measurements proved the formation of the new substances. Single-crystal X-ray diffraction studies confirmed proton transfer between the given alkaloid and 26DHBA, and the formation of N—H...O hydrogen bonds in both I and II. Unlike the caffeine cations in II, the theobromine cations in I are paired by noncovalent N—H...O=C interactions and a cyclic array is observed. As expected, the two hydroxy groups in the 26DHBA anion in both salts are involved in two intramolecular O—H...O hydrogen bonds. C—H...O and π–π interactions further stabilize the crystal structures of both compounds. Steady-state UV–Vis spectroscopy showed changes in the water solubility of xanthines after ionizable complex formation. The obtained salts I and II were also characterized by theoretical calculations, Fourier-transform IR spectroscopy (FT–IR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and elemental analysis.

scholarly journals Enhancement of solubility and dissolution rate of poorly water soluble raloxifene using microwave induced fusion method

2013 ◽  
Vol 49 (3) ◽  
pp. 571-578 ◽  
Author(s):  
Payal Hasmukhlal Patil ◽  
Veena Sailendra Belgamwar ◽  
Pratibha Ramratan Patil ◽  
Sanjay Javerilal Surana
Keyword(s):  
Dissolution Rate ◽  
Hydroxypropyl Methylcellulose ◽  
Microwave Treatment ◽  
Water Soluble ◽  
Fusion Method ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Wetting Properties ◽  
Poorly Soluble ◽  
Poorly Water Soluble

The objective of the present work was to enhance the solubility and dissolution rate of the drug raloxifene HCl (RLX), which is poorly soluble in water. The solubility of RLX was observed to increase with increasing concentration of hydroxypropyl methylcellulose (HPMC E5 LV). The optimized ratio for preparing a solid dispersion (SD) of RLX with HPMC E5 LV using the microwave-induced fusion method was 1:5 w/w. Microwave energy was used to prepare SDs. HPMC E5 LV was used as a hydrophilic carrier to enhance the solubility and dissolution rate of RLX. After microwave treatment, the drug and hydrophilic polymer are fused together, and the drug is converted from the crystalline form into an amorphous form. This was confirmed through scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies. These results suggested that the microwave method is a simple and efficient method of preparing SDs. The solubility and dissolution rate of the SDs were increased significantly compared with pure RLX due to the surfactant and wetting properties of HPMC E5 LV and the formation of molecular dispersions of the drug in HPMC E5 LV. It was concluded that the solubility and dissolution rate of RLX are increased significantly when an SD of the drug is prepared using the microwave-induced fusion method.

scholarly journals Intrinsic Dissolution Rate Profiling of Poorly Water-Soluble Compounds in Biorelevant Dissolution Media

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 493
Author(s):  
Alexandra Teleki ◽  
Olivia Nylander ◽  
Christel A.S. Bergström
Keyword(s):  
Dissolution Rate ◽  
Water Soluble ◽  
Small Scale ◽  
Intrinsic Dissolution ◽  
Intrinsic Dissolution Rate ◽  
Fed State ◽  
Pharmaceutical Ingredients ◽  
Biorelevant Dissolution ◽  
Intestinal Fluids ◽  
Simulated Intestinal Fluids

The intrinsic dissolution rate (IDR) of active pharmaceutical ingredients (API) is a key property that aids in early drug development, especially selecting formulation strategies to improve dissolution and thereby drug absorption in the intestine. Here, we developed a robust method for rapid, medium throughput screening of IDR and established the largest IDR dataset in open literature to date that can be used for pharmaceutical computational modeling. Eighteen compounds with diverse physicochemical properties were studied in both fasted and fed state simulated intestinal fluids. Dissolution profiles were measured in small-scale experimental assays using compound suspensions or discs. IDR measurements were not solely linked to API solubility in either dissolution media. Multivariate data analysis revealed that IDR strongly depends on compound partitioning into bile salt and phospholipid micelles in the simulated intestinal fluids, a process that in turn is governed by API lipophilicity, hydrophobicity, and ionization.

scholarly journals SOLID DOSAGE FORM DEVELOPMENT OF GLIBENCLAMIDE WITH INCREASING THE SOLUBILITY AND DISSOLUTION RATE USING COCRYSTALLIZATION

2018 ◽  
Vol 10 (6) ◽  
pp. 181
Author(s):  
Arif Budiman ◽  
Sandra Megantara ◽  
Putri Raraswati ◽  
Tazyinul Qoriah
Keyword(s):  
Dissolution Rate ◽  
Dosage Form ◽  
Crystallization Process ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Solid Dosage Form ◽  
Solid Dosage ◽  
Infra Red ◽  
Form Development

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.

Structures and physicochemical properties of vortioxetine salts

2016 ◽  
Vol 72 (5) ◽  
pp. 723-732 ◽  
Author(s):  
Xinbo Zhou ◽  
Xiurong Hu ◽  
Suxiang Wu ◽  
Jiali Ye ◽  
Mengying Sun ◽  
...  
Keyword(s):  
Antidepressant Drug ◽  
Drug Candidate ◽  
X Ray Diffraction ◽  
High Solubility ◽  
Scanning Calorimetry ◽  
Intrinsic Dissolution ◽  
X Ray ◽  
Acidic Proton ◽  
Water Ph ◽  
Ft Ir

In the present work, novel salts of the multimodal antidepressant drug vortioxetine (VT) were crystallized with pharmaceutically acceptable acids, aiming to improve the solubility of VT. The acids for VT were selected based on ΔpKabeing greater than 2 or 3. Salts of hydrobromic acid (HBr), hydrochloric acid (HCl),p-hydroxybenzoic acid (PHBA), saccharin (SAC) and L-aspartic acid (ASP) were reported. All salts were characterized by single-crystal X-ray diffraction, FT–IR, powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The acidic proton is transferred to the secondary N atom on the piperazine ring of VT, forming the charge-assisted hydrogen bond N+—H...X−(X= Cl, Br, O). Solubility and intrinsic dissolution rate (IDR) experiments were carried out in distilled water (pH = 7.0) to compare the solubilities of the salts with that of VT. The VT–ASP–H2O (1:1:2) salt showed 414 times higher solubility and 1722 times faster IDR compared with VT. VT–ASP–H2O (1:1:2) is a high solubility salt that is stable in a slurry experiment at 298 K in 95% ethanol. The experimental data for the VT–ASP–H2O (1:1:2) salt identify it as a promising drug candidate.

scholarly journals Preparation and evaluation of azithromycin binary solid dispersions using various polyethylene glycols for the improvement of the drug solubility and dissolution rate

2016 ◽  
Vol 52 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Ehsan Adeli
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Solid Dispersions ◽  
Water Soluble ◽  
Polyethylene Glycols ◽  
X Ray Diffraction ◽  
Drug Release Profile ◽  
Scanning Calorimetry ◽  
Peg 4000 ◽  
Poorly Soluble

ABSTRACT Azithromycin is a water-insoluble drug, with a very low bioavailability. In order to increase the solubility and dissolution rate, and consequently increase the bioavailability of poorly-soluble drugs (such as azithromycin), various techniques can be applied. One of such techniques is "solid dispersion". This technique is frequently used to improve the dissolution rate of poorly water-soluble compounds. Owing to its low solubility and dissolution rate, azithromycin does not have a suitable bioavailability. Therefore, the main purpose of this investigation was to increase the solubility and dissolution rate of azithromycin by preparing its solid dispersion, using different Polyethylene glycols (PEG). Preparations of solid dispersions and physical mixtures of azithromycin were made using PEG 4000, 6000, 8000, 12000 and 20000 in various ratios, based on the solvent evaporation method. From the studied drug release profile, it was discovered that the dissolution rate of the physical mixture, as the well as the solid dispersions, were higher than those of the drug alone. There was no chemical incompatibility between the drug and polymer from the observed Infrared (IR) spectra. Drug-polymer interactions were also investigated using Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Election Microscopy (SEM). In conclusion, the dissolution rate and solubility of azithromycin were found to improve significantly, using hydrophilic carriers, especially PEG 6000.

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