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

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.

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

Brazilian Journal of Pharmaceutical Sciences ◽

10.1590/s1984-82502016000100002 ◽

2016 ◽

Vol 52 (1) ◽

pp. 1-13 ◽

Cited By ~ 6

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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Combined Use of Polymers and Porous Materials to Enhance Cinnarizine Dissolution

Pharmaceutical Sciences ◽

10.15171/ps.2019.44 ◽

2019 ◽

Vol 25 (4) ◽

pp. 331-337

Author(s):

Maryam Maghsoodi ◽

Fatemeh Shahi

Keyword(s):

Porous Materials ◽

Dissolution Rate ◽

Water Soluble ◽

Scanning Calorimetry ◽

Water Soluble Drug ◽

Dissolution Behaviour ◽

Water Soluble Drugs ◽

Poorly Soluble ◽

Precipitation Inhibitor ◽

Poorly Water Soluble

Background: Loading of poorly water-soluble drugs on the porous materials has attracted great interest as an effective approach for enhancement of dissolution rate of drugs. The Aerosil (Ae) with porous structure is expected to facilitate the dissolution of drugs which is generally associated with precipitation. Thus, the purpose of this investigation was thus to develop a formulation which combines a precipitation inhibitor and a poorly soluble drug loaded Ae. Methods: A poorly water-soluble drug, Cinnarizine (CNZ) was used as a model, and Eudragit L100 (Eu) was used as a precipitation inhibitor. Formulations were produced by solvent evaporation and characterized by FT-IR and differential scanning calorimetry (DSC). Dissolution experiments were carried out in phosphate buffer (pH 6.8) under non-sink conditions. Results: DSC thermograms revealed that no crystalline structure of CNZ was present in CNZ-loaded Ae formulations and no long-range order was arranged upon loading of CNZ into Ae. In dissolution test, the CNZ-loaded Ae physically blended with Eu achieved a remarkedly higher CNZ concentration over the plain CNZ and over the CNZ-Eu co-loaded Ae. The dissolution rate of CNZ from the CNZ-loaded Ae was enhanced with increasing Ae amount and the dissolution was maximum when the ratio of CNZ: Ae was 1:10 CNZ: Ae. In addition, the precipitation inhibition was increased when the amount of Eu was high. Conclusion: The results of this work revealed that the dissolution behaviour of CNZ-loaded Ae is enhanced by physically blending of Eu as a suitable precipitation inhibitor.

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

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2009.2.2.5 ◽

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.

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Enhancement of Solubility and Dissolution Rate of Poorly Water Soluble Drug using Cosolvency and Solid Dispersion Techniques

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2008.1.4.6 ◽

1970 ◽

Vol 1 (4) ◽

pp. 349-356

Author(s):

Meka Lingam ◽

Vobalaboina Venkateswarlu

Keyword(s):

Dissolution Rate ◽

Solid Dispersions ◽

Physicochemical Characterization ◽

Aqueous Solubility ◽

Water Soluble ◽

Scanning Calorimetry ◽

Peg 400 ◽

Water Soluble Drug ◽

Poorly Water Soluble ◽

Poorly Water Soluble Drug

The low aqueous solubility of celecoxib (CB) and thus its low bioavailability is a problem. Thus, it is suggested to improve the solubility using cosolvency and solid dispersions techniques. Pure CB has solubility of 6.26±0.23µg/ml in water but increased solubility of CB was observed with increasing concentration of cosolvents like PEG 400, ethanol and propylene glycol. Highest solubility (791.06±15.57mg/ml) was observed with cosolvency technique containing the mixture of composition 10:80:10%v/v of water: PEG 400: ethanol. SDs with different polymers like PVP, PEG were prepared and subjected to physicochemical characterization using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), differential scanning calorimetry (DSC), solubility and dissolution studies. These studies reveals that CB exists mainly in amorphous form in prepared solid dispersions of PVP, PEG4000 and PEG6000 further it can also be confirmed by solubility and dissolution rate studies. Solid dispersions of PV5 and PV9 have shown highest saturation solubility and dissolution rate

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The Solution Improvement of Quercetin Using Spontaneous Emulsification Systems

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.859.139 ◽

2020 ◽

Vol 859 ◽

pp. 139-144

Author(s):

Yotsanan Weerapol ◽

Sukannika Tubtimsri

Keyword(s):

Photon Correlation Spectroscopy ◽

Correlation Spectroscopy ◽

Water Soluble ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Spontaneous Emulsification ◽

Photon Correlation ◽

X Ray ◽

Emulsion Formulation ◽

Poorly Water Soluble

Quercetin has been used for health promotion for instance anti-bacterial, anti-inflammatory, anti-coagulative, antineoplastic and antioxidant. The poorly water-soluble quercetin has been a significant problem of bioavailability for oral administration. The objective of this study was to improve the quercetin solubility by spontaneous emulsion formulation (SEF). SEF was fabricated by dissolved quercetin in mixture of polyoxyl 35 castor oil, diethylene glycol monoethy ether, caprylic/capric glyceride. The solid-SEF was obtained by incorporation with solid carrier adsorbent (magnesium aluminometasilicate). The photon correlation spectroscopy was used to determine the emulsion size of diluted SEF and solid-SEF. The power X-ray diffraction and differential scanning calorimetry were also employed to elucidate the powder of solid-SEF compared with unmodified quercetin. The dissolution profiled at 120 min of unmodified quercetin, SEF and solid-SEF was about 2%, 77% and 89%, respectively.

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Improving the Solubility of Aripiprazole by Multicomponent Crystallization

Crystals ◽

10.3390/cryst11040343 ◽

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.

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

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019v11i4.33802 ◽

2019 ◽

pp. 359-364 ◽

Cited By ~ 1

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.

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ENHANCEMENT OF GLIBENCLAMIDE DISSOLUTION RATE BY SOLID DISPERSION METHOD USING HPMC AND PVP

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019v11i5.34137 ◽

2019 ◽

pp. 19-24 ◽

Cited By ~ 1

Author(s):

ARIF BUDIMAN ◽

IYAN SOPYAN ◽

DENIA SEPTY RIYANDI

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Solid Dispersions ◽

Hydroxypropyl Methylcellulose ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

X Ray ◽

Rate Test ◽

Ft Ir

Objective: The aim of this study was to investigate the effects of changing in the proportions of the solid dispersion formula on the dissolution rate of glibenclamide. Methods: Solid dispersions were prepared by solvent evaporation method by using methanol as solvent, hydroxypropyl methylcellulose (HPMC) and polyvinyl pyrrolidone (PVP) as polymers. The prepared product was evaluated by the saturated solubility test and the dissolution rate test. The prepared product was characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) and Scanning Electron Microscopy (SEM). Results: The result showed solid dispersion with a ratio of glibenclamide: PVP: HPMC (1: 3: 6) has the highest increase in solubility (20 fold) compared to pure glibenclamide. This formula also showed an improvement in dissolution rate from 19.9±1.19% (pure glibenclamide) to 99±1.60% in 60 min. Characterization of FT-IR showed that no chemical reaction occurred in solid dispersion of glibenclamide. The results of X-ray diffraction analysis showed an amorphous form in all solid dispersion formulas. The results of DSC analysis showed that endothermic peak melting point of solid dispersion occurred, and the morphology of solid dispersion was more irregular than pure glibenclamide based on SEM characterization Conclusion: The solid dispersion of glibenclamide using PVP: HPMC as carriers can increase the solubility and dissolution rate compared to pure glibenclamide.

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Applicability of an Experimental Grade of Hydroxypropyl Methylcellulose Acetate Succinate as a Carrier for Formation of Solid Dispersion with Indomethacin

Pharmaceutics ◽

10.3390/pharmaceutics13030353 ◽

2021 ◽

Vol 13 (3) ◽

pp. 353

Author(s):

Hiroshi Ueda ◽

Yuya Hirakawa ◽

Hironori Tanaka ◽

Tetsuya Miyano ◽

Katsuji Sugita

Keyword(s):

Solid Dispersion ◽

Hydroxypropyl Methylcellulose ◽

Principal Component ◽

Amorphous Solid ◽

Water Soluble ◽

Amorphous Solid Dispersion ◽

Scanning Calorimetry ◽

Water Soluble Drugs ◽

Poorly Water Soluble ◽

Amorphous Drug

The transformation of a crystalline drug into an amorphous form is a promising way to enhance the oral bioavailability of poorly water-soluble drugs. Blending of a carrier, such as a hydrophilic polymer, with an amorphous drug is a widely used method to produce a solid dispersion and inhibit crystallization. This study investigates an experimental grade of hydroxypropyl methylcellulose acetate succinate, HPMCAS-MX (MX), as a solid dispersion carrier. Enhancement of thermal stability and reduction of the glass transition temperature (Tg) of MX compared with those of the conventional grade were evaluated through thermogravimetric analysis and differential scanning calorimetry (DSC). The formation of a homogeneous amorphous solid dispersion between MX and indomethacin was confirmed by X-ray powder diffraction analysis, DSC, and Raman mapping. It was observed that 10–30% MX did not act as an anti-plasticizer, but the utilization of >40% MX caused an increase in Tg and reduction of molecular mobility. This could be explained by a change in intermolecular interactions, inferred from infrared spectroscopy combined with principal component analysis. HPMCAS-MX exhibited similar performance to that of conventional-grade, HPMCAS-MG. Although HPMCAS-MX has thermal properties different from those of conventional-grade HPMCAS-MG, it retains its ability as a solid dispersion carrier.

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Poorly Water Soluble Drug Nanostructures via Surface Solvent Evaporation

Nano LIFE ◽

10.1142/s179398441540005x ◽

2015 ◽

Vol 05 (03) ◽

pp. 1540005 ◽

Cited By ~ 1

Author(s):

Michael Graham ◽

Yonghong Yang ◽

Aled D Roberts ◽

Haifei Zhang

Keyword(s):

Solvent Evaporation ◽

Water Soluble ◽

Aluminum Surface ◽

X Ray Diffraction ◽

Nanoparticle Suspension ◽

Water Soluble Drug ◽

Drug Compounds ◽

Poorly Soluble ◽

Poorly Water Soluble ◽

Poorly Water Soluble Drug

A high percentage of developed drug compounds are poorly soluble in water, which severely limits their applications. Nanotechnology has been used to address this issue. Here we describe a simple and versatile bottom-up approach for the preparation of drug nanostructures by surface solvent evaporation on aluminum surface and polymer-coated surface. Three poorly water soluble drug compounds, including griseofulvin (GF), curcumin and antimalarial compound SL-2-25 have been investigated as model compounds. The structures are mainly characterized by scanning electronic microscopy (SEM) while the GF nanoparticles are also examined by powder X-ray diffraction (PXRD) and thermogravimetric analysis (TGA). A variety of structures including microassemblies composed of nanoparticles, nanospheres and nanofibers have been produced. A sonication method can be employed to produce aqueous nanoparticle suspension.

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