scholarly journals Dissolution Enhancement of Atorvastatin Calcium by Cocrystallization

2019 ◽  
Vol 9 (4) ◽  
pp. 559-570 ◽  
Author(s):  
Reham Al-Kazemi ◽  
Yacoub Al-Basarah ◽  
Aly Nada
Keyword(s):  
Dissolution Rate ◽  
Dissolution Enhancement ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Atorvastatin Calcium ◽  
Molar Ratios ◽  
Poorly Soluble ◽  
Poorly Soluble Drug ◽  
Physical Mixtures ◽  
Biopharmaceutical Classification System

Purpose: To enhance the dissolution rate of the poorly soluble drug atorvastatin calcium (ATC) bycocrystallization with selected coformers. Enhancement of the dissolution rate and solubility of thedrug, which is classified as Class II of the Biopharmaceutical Classification System (BCS), is expectedto enhance the bioavailability.Methods: Two methods were used for preparing the cocrystals, solvent drop grinding (SDG) andsolvent evaporation (SE) method using 1:1, 1:3, and 1:10 drug-coformer molar ratios. Glucosaminehydrochloride (GluN) and nicotinamide (NIC) were investigated as coformers. The cocrystals,their physical mixtures, and the raw ATC were characterized by fourier transform infrared (FTIRspectroscopy), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), massspectroscopy (MS), scanning electron microscopy (SEM), solubility, and dissolution rate studies.Results: SDG and SE were effective in improving the dissolution rate of ATC with both coformers.Drug: coformer ratio 1:3 was optimum. The solubility values for ATC, GluN-, and NIC-cocrystals were26, to 35 and 50 μg/mL, respectively. The dissolution rate of ATC from cocrystals was > 90% after 5minutes, compared to 41% untreated ATC.Conclusion: Cocrystallization significantly improved the solubility and dissolution, in comparison tothe untreated ATC.<br />

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.

Manufacture of Ternary Solid Dispersions Composed of Nifedipine, Eudragit® E and Adsorbent

2011 ◽  
Vol 317-319 ◽  
pp. 185-188 ◽  
Author(s):  
Pornsak Sriamornsak ◽  
Srisuda Kontong ◽  
Yotsanan Weerapol ◽  
Jurairat Nunthanid ◽  
Srisagul Sungthongjeen ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersions ◽  
Ternary Systems ◽  
Dissolution Enhancement ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Ternary Solid Dispersions ◽  
Diffraction Patterns ◽  
Physical Mixtures

The aim of this study was to manufacture the ternary solid dispersions composed of nifedipine, Eudragit® E and adsorbent. Dissolution enhancement of nifedipine was also investigated. The inert solid carriers were added in the mixtures of nifedipine and Eudragit® E at varying ratios. The physicochemical properties of ternary systems, compared to physical mixtures, were analyzed using powder x-ray diffraction (PXRD) and differential scanning calorimetry (DSC). The dissolution of nifedipine from ternary systems was compared to the drug alone. The influence of drug:polymer: adsorbent ratio and type of adsorbent on the dissolution rate of the drug was also evaluated. The PXRD and DSC results of the systems with high amount of polymer showed that the drug was present in an amorphous form. On the other hand, the diffraction patterns and DSC thermograms of the physical mixtures revealed that to some extent the drug was present in a crystalline form. The results from this study demonstrated that an improvement in dissolution rate of nifedipine with Eudragit® E and adsorbents was obtained.

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 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.

scholarly journals Preparation and Characterization of a Novel Cocrystal of Atorvastatin Calcium with Succinic Acid Coformer

2019 ◽  
Vol 19 (3) ◽  
pp. 660
Author(s):  
Yudi Wicaksono ◽  
Dwi Setyawan ◽  
Siswandono Siswandono ◽  
Tri Agus Siswoyo
Keyword(s):  
Succinic Acid ◽  
Dissolution Rate ◽  
Intermolecular Hydrogen Bond ◽  
Acid Amide ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Atorvastatin Calcium ◽  
Hydrogen Bond Interactions

Preparation and characterization of a novel cocrystal of atorvastatin calcium with succinic acid coformer were successfully performed. This research aims to modify the crystalline form of atorvastatin calcium through cocrystallization with succinic acid coformer. The cocrystal was prepared by a solvent evaporation method and characterized by Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). The atorvastatin calcium-succinic acid cocrystal has new crystalline peaks at 2θ of 12.9, 18.2 and 26.7° indicating the formation of a new crystalline phase. The cocrystal showed the melting point at 205.7 °C with an enthalpy of fusion 30.2 J/g which is different from the initial components. The FTIR spectra of cocrystal showed the shifting of absorption peaks of groups of initial components indicating of formation of atorvastatin calcium-succinic acid cocrystal through acid–amide intermolecular hydrogen bond interactions. The solubility and dissolution test showed that the cocrystal has solubility and dissolution rate significantly higher than the solubility and dissolution rate of pure atorvastatin calcium.

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.

scholarly journals Co-Amorphous Formulations of Furosemide with Arginine and P-Glycoprotein Inhibitor Drugs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 171
Author(s):  
Marika Ruponen ◽  
Konsta Kettunen ◽  
Monica Santiago Pires ◽  
Riikka Laitinen
Keyword(s):  
Storage Conditions ◽  
Scanning Calorimetry ◽  
Glycoprotein P ◽  
Molar Ratios ◽  
P Glycoprotein ◽  
Permeation Studies ◽  
Poorly Soluble ◽  
Biopharmaceutics Classification ◽  
Permeability Assay ◽  
Simultaneous Dissolution

In this study, the amino acid arginine (ARG) and P-glycoprotein (P-gp) inhibitors verapamil hydrochloride (VER), piperine (PIP) and quercetin (QRT) were used as co-formers for co-amorphous mixtures of a Biopharmaceutics classification system (BCS) class IV drug, furosemide (FUR). FUR mixtures with VER, PIP and QRT were prepared by solvent evaporation, and mixtures with ARG were prepared by spray drying in 1:1 and 1:2 molar ratios. The solid-state properties of the mixtures were characterized with X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) in stability studies under different storage conditions. Simultaneous dissolution/permeation studies were conducted in side-by-side diffusion cells with a PAMPA (parallel artificial membrane permeability assay) membrane as a permeation barrier. It was observed with XRPD that ARG, VER and PIP formed co-amorphous mixtures with FUR at both molar ratios. DSC and FTIR revealed single glass transition values for the mixtures (except for FUR:VER 1:2), with the formation of intermolecular interactions between the components, especially salt formation between FUR and ARG. The co-amorphous mixtures were found to be stable for at least two months under an elevated temperature/humidity, except FUR:ARG 1:2, which was sensitive to humidity. The dissolution/permeation studies showed that only the co-amorphous FUR:ARG mixtures were able to enhance both the dissolution and permeation of FUR. Thus, it is concluded that formulating co-amorphous salts with ARG may be a promising option for poorly soluble/permeable FUR.

scholarly journals Solubility and Dissolution Enhancement of Atorvastatin Calcium using Solid Dispersion Adsorbate Technique

2019 ◽  
Vol 28 (2) ◽  
pp. 105-114
Author(s):  
Samer K. Ali ◽  
Eman B. H. Al-Khedairy
Keyword(s):  
Polyethylene Glycol ◽  
Solid Dispersion ◽  
Water Solubility ◽  
Drug Carrier ◽  
Solid Dispersions ◽  
Poloxamer 407 ◽  
Dissolution Enhancement ◽  
Drug Solubility ◽  
Scanning Calorimetry ◽  
Poorly Soluble

            Atorvastatin (ATR) is poorly soluble anti-hyperlipidemic drug; it belongs to the class II group according to the biopharmaceutical classification system (BCS) with low bioavailability due to its low solubility. Solid dispersions adsorbate is an effective technique for enhancing the solubility and dissolution of poorly soluble drugs.           The present study aims to enhance the solubility and dissolution rate of ATR using solid dispersion adsorption technique in comparison with ordinary solid dispersion. polyethylene glycol 4000 (PEG 4000), polyethylene glycol 6000 (PEG 6000), Poloxamer188 and Poloxamer 407were used as hydrophilic carriers and Aerosil 200, Aerosil 300 and magnesium aluminium silicate (MAS) as adsorbents.            All solid dispersion adsorbate (SDA) formulas  were prepared in ratios of 1:1:1  (drug: carrier: adsorbent) and evaluated for their water solubility, percentage yield, drug content,  , dissolution, crystal structure using  X-ray powder diffraction (XRD) and Differential Scanning Calorimetry (DSC)  studies and Fourier Transform Infrared Spectroscopy (FTIR) for determination the drug-carrier- adsorbate interaction.                The prepared (SDA) showed significant improvement of drug solubility in all prepared formula. Best result was obtained with formula SDA12(ATR :Poloxamer407 : MAS 1:1:1) that showed 8.07 and 5.38  fold increase in solubility compared to  solubility of pure ATR and  solid dispersion(SD4) (Atorvastatin: Poloxamer 407 1:1) respectively due to increased wettability and reduced crystallinity of the drug which leads to improve drug solubility  and  dissolution .

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

INDIAN DRUGS ◽  
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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