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

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.

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Enhancement of Dissolution Rate of Daidzein in Ternary Solid Dispersions

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.550-553.1000 ◽

2012 ◽

Vol 550-553 ◽

pp. 1000-1004 ◽

Cited By ~ 1

Author(s):

Hui Wang ◽

Hong Xin Xu ◽

Na Zhang ◽

Lian Dong Hu

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Drug Carrier ◽

Solid Dispersions ◽

X Ray Diffraction ◽

Positive Role ◽

X Ray ◽

Dissolution Tests ◽

Ternary Solid Dispersions ◽

Pvp K30

The purpose of this study was to enhance the dissolution rate of daidzein (DZ) by solid dispersions. DZ solid dispersion was prepared by solvent method, with PVP K30 and surfactant as carriers. The influences of drug-carrier proportion, the kind of surfactant and the amount of surfactant on the dissolution of DZ were examined. Solid dispersions were characterized by infrared spectroscopy (IR), X-ray diffraction spectroscopy, and dissolution tests. When appropriate amount of poloxamer was added into the solid dispersion, the dissolution of DZ could be improved obviously. The data of IR showed that the absence of well-defined drug-polymer interactions. The data of X-ray diffraction showed that the drug might exist in the form of amorphism or molecule in solid dispersions. Both the binary and ternary solid dispersions enhanced the dissolution of DZ. Moreover, poloxamer played an important positive role in improving the dissolution rate of DZ in the solid dispersion.

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Enhancing the Solubility of Curcumin Using a Solid Dispersion System with Hydroxypropyl-β-Cyclodextrin Prepared by Grinding, Freeze-Drying, and Common Solvent Evaporation Methods

Pharmacy ◽

10.3390/pharmacy8040203 ◽

2020 ◽

Vol 8 (4) ◽

pp. 203

Author(s):

Nguyen Ngoc Sao Mai ◽

Riko Nakai ◽

Yayoi Kawano ◽

Takehisa Hanawa

Keyword(s):

Freeze Drying ◽

Solid Dispersions ◽

Solvent Evaporation ◽

Order Complex ◽

Drug Solubility ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

X Ray ◽

Dissolution Studies ◽

Physical Mixtures

Cyclodextrins (CDs) and their derivatives significantly increase drug solubility by forming drug/CD complexes known as solid dispersions (SDs), which consist of an inclusion complex (IC), where the drug is entrapped within the CD cavity, and a non-IC. Here, the SDs of curcumin (CUR) and hydroxypropyl-β-cyclodextrin (HPβCD) were prepared using the grinding, freeze-drying (FD), and common solvent evaporation (CSE) methods and were physicochemically characterized using solubility, powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry, and dissolution studies. The second or higher order complex of CUR-HPβCD indicated the co-existence of ICs and non-ICs known as the SD system. When comparing the soluble drug amount with CUR crystals, the solubility of SDs was enhanced by up to 299-, 180-, and 489-fold, corresponding to the ground mixtures (GMs), freeze-drying mixtures (FDs), and common solvent evaporation mixtures (CSEs), respectively. The total transformation into the amorphous phase of CUR was observed in GMs and in CSE12, CSE14, and CSE18. The drug was well dispersed within HPβCD in GMs and CSEs, suggesting the formation of hydrogen bonds between CUR and HPβCD, whereas the dispersed behavior of FDs was similar to that of physical mixtures. In SDs, the melting temperature of CUR was in an increased order of CUR in 1:2 ICs, CUR in 1:1 ICs, and CUR crystals. The dissolution rate of CUR was positively improved as the amount of HPβCD in SDs increased. The SD system consisting of CUR and HPβCD significantly increased the drug solubility compared to ICs.

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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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Dissolution Enhancement of Atorvastatin Calcium by Cocrystallization

Advanced Pharmaceutical Bulletin ◽

10.15171/apb.2019.064 ◽

2019 ◽

Vol 9 (4) ◽

pp. 559-570 ◽

Cited By ~ 1

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 />

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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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Structure and properties of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)/poly(L-lactic acid) quasi core/sheath melt-electrospun microfibers

Textile Research Journal ◽

10.1177/0040517518779997 ◽

2018 ◽

Vol 89 (9) ◽

pp. 1770-1781 ◽

Cited By ~ 1

Author(s):

Huaizhong Xu ◽

Benedict Bauer ◽

Masaki Yamamoto ◽

Hideki Yamane

Keyword(s):

Mechanical Properties ◽

Tensile Strength ◽

Lactic Acid ◽

Tensile Tests ◽

Processing Parameters ◽

Structure And Properties ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

X Ray ◽

Diffraction Patterns

A facile route was proposed to fabricate core–sheath microfibers, and the relationships among processing parameters, crystalline structures and the mechanical properties were investigated. The compression molded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBH)/poly(L-lactic acid) (PLLA) strip enhanced the spinnability of PHBH and the mechanical properties of PLLA as well. The core–sheath ratio of the fibers was determined by the prefab strip, while the PLLA sheath component did not completely cover the PHBH core component due to the weak interfacial tension between the melts of PHBH and PLLA. A rotational target was applied to collect aligned fibers, which were further drawn in a water bath. The tensile strength and the modulus of as-spun and drawn fibers increased with increasing the take-up velocities. When the take-up velocity was above 500 m/min, the jet became unstable and started to break up at the tip of the Taylor cone, decreasing the mechanical properties of the fibers. The drawing process facilitated the crystallization of PLLA and PHBH, and the tensile strength and the modulus increased linearly with the increasing the draw ratio. The crystal information displayed from wide-angle X-ray diffraction patterns and differential scanning calorimetry heating curves supported the results of the tensile tests.

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

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i6.29257 ◽

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.

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Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties

Pharmaceutics ◽

10.3390/pharmaceutics12030289 ◽

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.

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Compression-Induced Phase Transitions of Bicalutamide

Pharmaceutics ◽

10.3390/pharmaceutics12050438 ◽

2020 ◽

Vol 12 (5) ◽

pp. 438 ◽

Cited By ~ 1

Author(s):

Joanna Szafraniec-Szczęsny ◽

Agata Antosik-Rogóż ◽

Justyna Knapik-Kowalczuk ◽

Mateusz Kurek ◽

Ewa Szefer ◽

...

Keyword(s):

Solid Dispersions ◽

Amorphous Solid ◽

Active Pharmaceutical Ingredient ◽

X Ray Diffraction ◽

Scanning Calorimetry ◽

Amorphous Solid Dispersions ◽

X Ray ◽

High Propensity ◽

Poorly Soluble ◽

Amorphous Drug

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.

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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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