The Effect of Cooling on the Degree of Crystallinity, Solid-State Properties, and Dissolution Rate of Multi-Component Hot-Melt Extruded Solid Dispersions

The effect of cooling on the degree of crystallinity, solid-state and dissolution properties of multi-component hot-melt extruded solid dispersions [SD] is of great interest for the successful formulation of amorphous SDs and is an area that is unreported, especially in the context of improving the stability of these specific systems. The thermal solid-state properties, degree of crystallinity, drug–polymer interactions, solubility and physical stability over time were investigated. X-ray powder diffraction [XRPD] and hyper differential scanning calorimetry [DSC] confirmed that indomethacin [INM] was converted to the amorphous state; however, the addition of poloxamer 407 [P407] had a significant effect on the degree of crystallinity and the solubility of the SD formulations. Spectroscopy studies identified the mechanism of interaction and solubility studies, showing a higher dissolution rate compared to amorphous and pure INM in pH 1.2 with a kinetic solubility of 20.63 µg/mL and 34.7 µg/mL after 3 and 24 h. XRPD confirmed that INM remained amorphous after 5 months stability testing in solid solutions with Poly(vinylpyrrolidone-co-vinyl acetate) [PVP VA64] and Plasdone S-630 [PL-S630]. Although cooling had a significant effect on the degree of crystallinity and on solubility of INM, the cooling method used did not have any significant effect on the amorphous stability of INM over time.

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FABRICATION AND EVALUATION OF SOLID DISPERSION CONTAINING GLIBENCLAMIDE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i8.26236 ◽

2018 ◽

Vol 11 (8) ◽

pp. 158

Author(s):

Nikita Sehgal ◽

Vishal Gupta N ◽

Gowda Dv ◽

Sivadasu P

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Solid Dispersions ◽

Amorphous State ◽

In Vitro Dissolution ◽

Dissolution Profile ◽

Stability Studies ◽

Scanning Calorimetry ◽

Dsc Studies

Objective: The aim of the present study was to increase the dissolution rate of glibenclamide (GLIB) by molecular dispersion of drug in the polymeric matrix of Pluronic F-127.Methods: GLIB-loaded solid dispersions were formulated by fusion method. The formulated solid dispersions were characterized for scanning electron microscopy (SEM), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), and evaluated for percentage yield, drug content, solubility, and in vitro dissolution profile, and stability studies were conducted as per International Conference on Harmonisation guidelines Q1A in stability chamber, both at intermediate and accelerated conditions.Results: Both XRD and DSC studies suggested that crystalline GLIB was converted to amorphous form after loading into carrier. SEM studies revealed that the prepared solid dispersions were in the form of irregular particles with the absence of crystalline material. Due to this conversion of crystalline to amorphous state, formulated solid dispersions had shown improved dissolution rate profile of GLIB and stability studies suggested that formulated solid dispersions showed no significant changes in appearance and also in drug content.Conclusion: Thus, from the obtained results, it can be concluded that dissolution profile of GLIB can be improved by formulating as solid dispersion.

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An Approach to Enhance Dissolution Rate of Tamoxifen Citrate

BioMed Research International ◽

10.1155/2019/2161348 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Nagaraja SreeHarsha ◽

Jagadeesh G. Hiremath ◽

Swathi Chilukuri ◽

Rajesh Kumar Aitha ◽

Bandar E. Al-Dhubiab ◽

...

Keyword(s):

Dissolution Rate ◽

Solid Dispersions ◽

Amorphous State ◽

Binary Complex ◽

Physicochemical Interaction ◽

Dissolution Profile ◽

Scanning Calorimetry ◽

Drug Content ◽

Tamoxifen Citrate

We tested the solubility and dissolution of tamoxifen citrate to ascertain the optimal conditions for faster dissolution. Using the solvent evaporation method and hydrophilic carriers, we formulated tamoxifen citrate (TC) that contained solid dispersions (SDs). We increased the solubility and dissolution rate of TC with a solid dispersion system that consisted of polyethylene glycol (PEG-6000), beta-cyclodextrin (β-CD), and a combination of carriers. Physicochemical characteristics of solubility (mg/ml) were found to be 0.987±0.04 (water), 1.324±0.05 (6.8pH PBS), and 1.156±0.03 (7.4 pH PBS) for F5 formulation, percentage yield was between 98.74 ± 1.11% and 99.06 ± 0.58%, drug content was between 98.06±0.58 and 99.06±1.10, and dissolution studies binary complex showed a faster release of TC as compared to a single polymer and pure drug. Furthermore, thermal properties, physicochemical drug and polymer interaction, crystal properties, and morphology were determined using differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), X-ray differential studies, and scanning electron microscopy. We used the same proportion of carrier concentrations of the formulations to calculate the solubility of TC. Our results demonstrated that increased concentrations of β-C yielded an improved solubility of TC, which was two times higher than pure TC. The uniformity in drug content was 97.99 %. A quicker drug release occurred from the binary complex formulation as seen in the dissolution profile. FTIR demonstrated an absence in the physicochemical interaction between the drug and carriers. The drug was also found to be dispersed in the amorphous state as revealed by DSC and XRD. The drug concentration did not vary during various storage conditions. Our in vivo studies demonstrated that SD displayed significantly higher values of Cmax (p < 0.05) and AUC0-24 (p < 0.05) as compared to free TC. Furthermore, Tmax in SD was significantly lower (p < 0.05), as compared to free TC.

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Artemether-Soluplus Hot-Melt Extrudate Solid Dispersion Systems for Solubility and Dissolution Rate Enhancement with Amorphous State Characteristics

Journal of Pharmaceutics ◽

10.1155/2013/151432 ◽

2013 ◽

Vol 2013 ◽

pp. 1-15 ◽

Cited By ~ 3

Author(s):

Ritesh A. Fule ◽

Tarique S. Meer ◽

Ajay R. Sav ◽

Purnima D. Amin

Keyword(s):

Dissolution Rate ◽

Solid Dispersion ◽

Amorphous State ◽

Polymer Melt ◽

Aqueous Solubility ◽

Dissolution Profile ◽

Scanning Calorimetry ◽

Peg 400 ◽

Hot Melt

This work studied artemether (ARTM) solid dispersion (SD) formulation using mixture of polymer excipient Soluplus, PEG 400, Lutrol F127, and Lutrol F68 melts at temperatures lower than the melting point of ARTM using a laboratory-size, single-screw rotating batch extruder. The effects of three surfactants PEG 400, Lutrol F127, and Lutrol F68 and parameters like mixing temperature, screw rotating speed, and residence time were systematically studied. SEM, XRD, and FT-IR were employed to investigate the evolution of ARTM’s dissolution into the molten excipient. Differential scanning calorimetry (DSC) was used to quantitatively study the melting enthalpy evolution of the drug. The results showed that the dissolution rate increased with increasing the ratio of polymer and surfactant to that of drug. It was concluded that the dissolution of the drug in the polymer melt is a convective diffusion process and that laminar distributive mixing can significantly enhance the dissolution rate. The aqueous solubility and dissolution rate of prepared solid dispersion were significantly enhanced. In vitro antimalarial studies revealed marked improvement in IC50 values. Thus hot-melt extrusion (HME) is a promising technology for improving solubility and dissolution profile of ARTM.

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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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Preparation and Characterization of Talc Filled Thermoplastic Polyurethane/Polypropylene Blends

Journal of Polymers ◽

10.1155/2014/289283 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Emi Govorčin Bajsić ◽

Vesna Rek ◽

Ivana Ćosić

Keyword(s):

Thermal Properties ◽

Thermoplastic Polyurethane ◽

Mechanical Analysis ◽

Degree Of Crystallinity ◽

Scanning Calorimetry ◽

Polypropylene Blends ◽

Pp Blends ◽

The Degree Of Crystallinity ◽

Better Than

The effect of the addition of talc on the morphology and thermal properties of blends of thermoplastic polyurethane (TPU) and polypropylene (PP) was investigated. The blends of TPU and PP are incompatible because of large differences in polarities between the nonpolar crystalline PP and polar TPU and high interfacial tensions. The interaction between TPU and PP can be improved by using talc as reinforcing filler. The morphology was observed by means of scanning electron microscopy (SEM). The thermal properties of the neat polymers and unfilled and talc filled TPU/PP blends were studied by using dynamic mechanical analysis (DMA), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The addition of talc in TPU/PP blends improved miscibility in all investigated TPU/T/PP blends. The DSC results for talc filled TPU/PP blends show that the degree of crystallinity increased, which is due to the nucleating effect induced by talc particles. The reason for the increased storage modulus of blends with the incorporation of talc is due to the improved interface between polymers and filler. According to TGA results, the addition of talc enhanced thermal stability. The homogeneity of the talc filled TPU/PP blends is better than unfilled TPU/PP blends.

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Impact of environmental agents on non-woven polylactide/natural rubber agrofiber

E3S Web of Conferences ◽

10.1051/e3sconf/202128507034 ◽

2021 ◽

Vol 285 ◽

pp. 07034

Author(s):

Yulia Tertyshnaya ◽

Maksim Zakharov ◽

Alina Ivanitskikh ◽

Anatoliy Popov

Keyword(s):

Natural Rubber ◽

Uv Irradiation ◽

Thermal Characteristics ◽

Degree Of Crystallinity ◽

Distilled Water ◽

Fibrous Materials ◽

Scanning Calorimetry ◽

Melting Temperatures ◽

Environmental Agents ◽

The Degree Of Crystallinity

In the work an eco-friendly non-woven fiber made of polylactide and natural rubber with a rubber content from 0 to 15 wt.% was obtained by electrospinning. The influence of distilled water and UV irradiation on the agrofibers has been investigated. The water sorption test showed that the addition of natural rubber into the polylactide matrix does not significantly affect the degree of water absorption of the fibrous materials, which is in the range of 49-50.6%. Thermal characteristics after 180 days of degradation in distilled water at 22±2 oC and UV irradiation at a wavelength of 365 nm during 100 hours were determined using the differential scanning calorimetry. Changes in the values for glass transition and melting temperatures, and the degree of crystallinity were determined.

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

Iraqi Journal of Pharmaceutical Sciences ( P-ISSN 1683 - 3597 E-ISSN 2521 - 3512) ◽

10.31351/vol28iss2pp105-114 ◽

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 .

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Fusion as an Approach to Enhance Dissolution Rate of a Poorly Water-Soluble Drug (Curcurmin)

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.393-395.119 ◽

2011 ◽

Vol 393-395 ◽

pp. 119-122

Author(s):

Dong Hua Wan ◽

Fen Lin ◽

Qu Xiang Liao

Keyword(s):

Dissolution Rate ◽

Drug Loading ◽

Solid Dispersions ◽

Gastric Fluid ◽

Molecular State ◽

Water Soluble ◽

Drug Dissolution ◽

Simulated Gastric Fluid ◽

Scanning Calorimetry ◽

Rate Improvement

It’s well known that curcumin is practically insoluble in water. Therefore, to improve the drug dissolution rate, fusion approach was employed to prepare curcumin solid dispersions (SDs) in the carrier Pluronic F68 with three different drug loads. The dissolution rate of curcumin from the SDs was measured at simulated gastric fluid. The concentration of the dissolved drug in the medium was determined by HPLC. The dissolution rates of the formulations were dependent on the drug loading in SDs. 92.2% CUR was dissolved in 10 min from the SDs with 8.97% drug load, whereas the amounts of drug released were 65.8% and 84.2% within 120 min from the SDs with 18.9% and 29.0% drug loads, respectively. The Fourier transform infrared spectra indicated hydrogen bond between the drug and carrier. Furthermore, their physicochemical properties were well investigated using differential scanning calorimetry and X-ray diffraction. In the dispersions containing 8.97% CUR, the drug was in the molecular state. At a composition of approximately 18.9%, CUR was dispersed as micro-fine crystals. These interesting results indicate that the physical states of the drug in the carrier, which are governed by the drug loading, can affect the dissolution rate improvement.

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Thermal solid-state Z/E isomerization of 2-alkylidene-4-oxothiazolidines: Effects of non-covalent interactions

Journal of the Serbian Chemical Society ◽

10.2298/jsc100607038d ◽

2011 ◽

Vol 76 (3) ◽

pp. 317-328 ◽

Cited By ~ 4

Author(s):

Zdravko Dzambaski ◽

Milovan Stojanovic ◽

Marija Baranac-Stojanovic ◽

Dragica Minic ◽

Rade Markovic

Keyword(s):

Solid State ◽

1H Nmr Spectroscopy ◽

Amorphous State ◽

Intramolecular Hydrogen Bonding ◽

Scanning Calorimetry ◽

X Ray ◽

Configurational Isomerization ◽

Non Covalent Interactions ◽

Intramolecular Hydrogen ◽

Covalent Interactions

Configurational isomerization of stereo-defined 5-substituted and unsubstituted 2-alkylidene-4-oxothiazolidines 1 in the solid state, giving the Z/E mixtures in various ratios, was investigated by 1H-NMR spectroscopy, X-ray powder crystallography and differential scanning calorimetry (DSC). The Z/E composition can be rationalized in terms of non-covalent interactions, involving intermolecular and intramolecular hydrogen bonding and directional non-bonded 1,5-type S...O interactions. X-Ray powder crystallography, using selected crystalline (Z)-4- oxothiazolidine substrates, revealed transformation to the amorphous state during the irreversible Z ? E process. A correlation between previous results on the Z/E isomerization in solution and now in the solid state was established.

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The Effect of Crystallinity on the Toughness of Cast Polyamide 6 Rods with Different Diameters

Polymers ◽

10.3390/polym12020293 ◽

2020 ◽

Vol 12 (2) ◽

pp. 293

Author(s):

Miklós Odrobina ◽

Tamás Deák ◽

László Székely ◽

Tamás Mankovits ◽

Róbert Zsolt Keresztes ◽

...

Keyword(s):

Impact Strength ◽

Impact Test ◽

Charpy Impact ◽

Polyamide 6 ◽

Degree Of Crystallinity ◽

Scanning Calorimetry ◽

Tensile Impact ◽

Different Diameters ◽

The Impact ◽

The Degree Of Crystallinity

The present paper concentrates on the toughness and the degree of crystallinity of the magnesium-catalyzed polyamide 6 rods cast in different diametres, which are commonly used for gear manufacturing. Its toughness cannot be regarded as a constant feature due to the casting technology. The mechanical properties of the semi-finished products are sensitive to the manufactured dimension, e.g., cast diameter, which are investigated by the Charpy impact test and tensile impact test. It is generally accepted that the impact strength and tensile-impact strength correlate with the degree of crystallinity beside many other material’s feature. Crystallinity is evaluated by Differential Scanning Calorimetry. The aim of this study is to determine the relationship between toughness and crystallinity of the magnesium-catalyzed cast PA6 rods with different diameters. For the research cast rods between 40 and 300 mm diameter were selected in seven-dimensional steps. Based on the results, it was found that the toughness depends strongly on the diameter size. Furthermore, it is proved that the crystallinity explains 62.3% of the variation of the Charpy’s impact strengths, while the tensile impact method was not suitable to detect the difference between the test samples.

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