Study of the physicochemical properties and oral bioavailability of the solid dispersion of cantharidin with polyethylene glycol PEG 4000

Glimepiride (GMP) is poorly water soluble drug, so solubility is the main constraint for its oral bioavailability. Because, poor aqueous solubility and slow dissolution rate of the glimepiride lead to irreproducible clinical response or therapeutic failure in some cases due to sub therapeutic plasma drug levels. In this study, binary and ternary solid dispersion of glimepiride were prepared with polyethylene glycol 6000 (PEG 6000) and polyethylene glycol 4000 (PEG 4000) at different weight ratios using the solvent evaporation and melting method. It was found the drug was released 0.46% after 5 minutes and only 15.83% within 60 minutes from active glimepiride on the other hand the release pattern of glimepiride from the binary formulation containing PEG 4000 in 1:5 (Formulation coding: G5) showed the best result. It was found that the ternary different SD formulation containing(PEG4000:Glimepiride:Povidone) In ratio 1:1:0.25 (Formulation coding were : G13) showed the best result. The drug was changed to amorphous form after solid dispersion. Itwas also evident that solid dispersions improve solubility of drug particles thus enhancing dissolution characteristics of drugs they increase the oral bioavailability. Peer Review History: UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 4.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Name: Dr. Mohammed Abdel-Wahab Sayed Abourehab Affiliation: Umm Al-Qura University; Makkah Al-Mukarramah, Saudi Arabia E-mail: [email protected] Name: Dr. Evren Alğin Yapar Affiliation: Turkish Medicines and Medical Devices Agency, Turkiye E-mail: [email protected] Comments of reviewer(s):

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EVALUATING THE BEST POLYETHYLENE GLYCOL AS SOLID DISPERSION CARRIER BY TAKING ETORICOXIB AS A MODEL DRUG

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i3.30251 ◽

2019 ◽

pp. 250-255

Author(s):

HEMANTH A ◽

HINDUSTAN ABDUL AHAD ◽

DEVANNA N

Keyword(s):

Polyethylene Glycol ◽

Solid Dispersion ◽

Solid Dispersions ◽

Physicochemical Characteristics ◽

Peg 6000 ◽

Good Solubility ◽

Peg 4000 ◽

Tablet Compression ◽

Model Drug ◽

Peg 8000

Objective: The main objective of the current research is focused in discovering the best polyethylene glycol (PEG) as solid dispersion carrier using etoricoxib (ECB) as a model drug. Methods: Varieties of PEG, namely PEG - 3350, PEG - 4000, PEG - 6000, PEG - 8000, and PEG - 20000, were evaluated as a carrier for making ECB solid dispersions. ECB:PEG was taken in the ratios of 1:1, 1:2, 1:4, and 1:6. The solid dispersions were prepared by microwave fusion method and compressed using 8 station tablet compression machine. The fabricated solid dispersion tablets were tested for physicochemical characteristics and drug release rates. The release of ECB from the prepared solid dispersions was further analyzed kinetically using the first order and Hixson-Crowell’s plots. Results: All the solid dispersion batches were shown satisfactory physicochemical characteristics. ECB solid dispersion batches with PEG - 6000 showed good solubility in distilled water (up to 2.29±0.01 μg/ml) and in 0.1 N HCl (up to 2.18±0.01 μg/ml) when compared with ECB alone (0.21±0.01 μg/ml and 0.32±0.01 μg/ml). The prepared solid dispersions with PEG 6000 are shown good ECB release. Conclusion: Among PEG carriers, PEG - 6000 was found to be the best carrier for increasing the solubility and release rate of ECB form the solid dispersions compared to PEG - 3350, PEG - 4000, PEG - 8000, and PEG - 20000.

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Enhancement of solubility and oral bioavailability of manidipine by formation of ternary solid dispersion with d-α-tocopherol polyethylene glycol 1000 succinate and copovidone

Drug Development and Industrial Pharmacy ◽

10.1080/03639045.2017.1371731 ◽

2017 ◽

Vol 43 (12) ◽

pp. 2064-2075 ◽

Cited By ~ 7

Author(s):

Benchawan Chamsai ◽

Sontaya Limmatvapirat ◽

Srisagul Sungthongjeen ◽

Pornsak Sriamornsak

Keyword(s):

Polyethylene Glycol ◽

Solid Dispersion ◽

Oral Bioavailability ◽

Polyethylene Glycol 1000 ◽

Ternary Solid Dispersion

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Preparation and optimization of a resveratrol solid dispersion to improve the physicochemical properties and oral bioavailability of resveratrol

Journal of Dispersion Science and Technology ◽

10.1080/01932691.2020.1822861 ◽

2021 ◽

Vol 42 (4) ◽

pp. 605-613

Author(s):

Liyan Wang ◽

Aiping Tan ◽

Shan Zhao ◽

Jianbin Zhang ◽

Deshi Dong ◽

...

Keyword(s):

Physicochemical Properties ◽

Solid Dispersion ◽

Oral Bioavailability

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Improving the dissolution and oral bioavailability of the poorly water-soluble drug aloe-emodin by solid dispersion with polyethylene glycol 6000

Drug Development Research ◽

10.1002/ddr.20312 ◽

2009 ◽

Vol 70 (5) ◽

pp. 363-369 ◽

Cited By ~ 10

Author(s):

Hao-gang Duan ◽

Yu-hui Wei ◽

Bo-xia Li ◽

Hong-yan Qin ◽

Xin-an Wu

Keyword(s):

Polyethylene Glycol ◽

Solid Dispersion ◽

Oral Bioavailability ◽

Water Soluble ◽

Water Soluble Drug ◽

Aloe Emodin ◽

Poorly Water Soluble ◽

Polyethylene Glycol 6000 ◽

Poorly Water Soluble Drug

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Enhanced Bioavailability and Efficacy of Silymarin Solid Dispersion in Rats with Acetaminophen-Induced Hepatotoxicity

Pharmaceutics ◽

10.3390/pharmaceutics13050628 ◽

2021 ◽

Vol 13 (5) ◽

pp. 628

Author(s):

Im-Sook Song ◽

So-Jeong Nam ◽

Ji-Hyeon Jeon ◽

Soo-Jin Park ◽

Min-Koo Choi

Keyword(s):

Alkaline Phosphatase ◽

Polyethylene Glycol ◽

Oral Administration ◽

Solid Dispersion ◽

Active Component ◽

Efflux Pump ◽

Therapeutic Effects ◽

Permeation Enhancer ◽

Efflux Ratio ◽

Polyethylene Glycol 1000

We evaluated the bioavailability, liver distribution, and efficacy of silymarin-D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) solid dispersion (silymarin-SD) in rats with acetaminophen-induced hepatotoxicity (APAP) compared with silymarin alone. The solubility of silybin, the major and active component of silymarin, in the silymarin-SD group increased 23-fold compared with the silymarin group. The absorptive permeability of silybin increased by 4.6-fold and its efflux ratio decreased from 5.5 to 0.6 in the presence of TPGS. The results suggested that TPGS functioned as a solubilizing agent and permeation enhancer by inhibiting efflux pump. Thus, silybin concentrations in plasma and liver were increased in the silymarin-SD group and liver distribution increased 3.4-fold after repeated oral administration of silymarin-SD (20 mg/kg as silybin) for five consecutive days compared with that of silymarin alone (20 mg/kg as silybin). Based on higher liver silybin concentrations in the silymarin-SD group, the therapeutic effects of silymarin-SD in hepatotoxic rats were evaluated and compared with silymarin administration only. Elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels were significantly decreased by silymarin-SD, silymarin, and TPGS treatments, but these decreases were much higher in silymarin-SD animals than in those treated with silymarin or TPGS. In conclusion, silymarin-SD (20 mg/kg as silybin, three times per day for 5 days) exhibited hepatoprotective properties toward hepatotoxic rats and these properties were superior to silymarin alone, which may be attributed to increased solubility, enhanced intestinal permeability, and increased liver distribution of the silymarin-SD formulation.

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Enhanced Oral Bioavailability of Resveratrol by Using Neutralized Eudragit E Solid Dispersion Prepared via Spray Drying

Antioxidants ◽

10.3390/antiox10010090 ◽

2021 ◽

Vol 10 (1) ◽

pp. 90

Author(s):

Eun-Sol Ha ◽

Du Hyung Choi ◽

In-hwan Baek ◽

Heejun Park ◽

Min-Soo Kim

Keyword(s):

Spray Drying ◽

Solid Dispersion ◽

Oral Bioavailability ◽

Solid Dispersions ◽

Amorphous Solid ◽

Pharmaceutical Products ◽

In Vitro Dissolution ◽

Dependent Manner ◽

Amorphous Solid Dispersions ◽

Eudragit E

In this study, we designed amorphous solid dispersions based on Eudragit E/HCl (neutralized Eudragit E using hydrochloric acid) to maximize the dissolution of trans-resveratrol. Solid-state characterization of amorphous solid dispersions of trans-resveratrol was performed using powder X-ray diffraction, scanning electron microscopy, and particle size measurements. In addition, an in vitro dissolution study and an in vivo pharmacokinetic study in rats were carried out. Among the tested polymers, Eudragit E/HCl was the most effective solid dispersion for the solubilization of trans-resveratrol. Eudragit E/HCl significantly inhibited the precipitation of trans-resveratrol in a pH 1.2 dissolution medium in a dose-dependent manner. The amorphous Eudragit E/HCl solid dispersion at a trans-resveratrol/polymer ratio of 10/90 exhibited a high degree of supersaturation without trans-resveratrol precipitation for at least 48 h by the formation of Eudragit E/HCl micelles. In rats, the absolute oral bioavailability (F%) of trans-resveratrol from Eudragit E/HCl solid dispersion (10/90) was estimated to be 40%. Therefore, trans-resveratrol-loaded Eudragit E/HCl solid dispersions prepared by spray drying offer a promising formulation strategy with high oral bioavailability for developing high-quality health supplements, nutraceutical, and pharmaceutical products.

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Effect of surfactant on the in vitro dissolution and the oral bioavailability of a weakly basic drug from an amorphous solid dispersion

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2021.105836 ◽

2021 ◽

pp. 105836

Author(s):

Nguyen-Thach Tung ◽

Cao-Son Tran ◽

Tran-Linh Nguyen ◽

Thi-Minh-Hue Pham ◽

Sang-Cheol Chi ◽

...

Keyword(s):

Solid Dispersion ◽

Oral Bioavailability ◽

Amorphous Solid ◽

In Vitro Dissolution ◽

Amorphous Solid Dispersion ◽

Basic Drug

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The Influence of Temperature and Viscosity of Polyethylene Glycol on the Rate of Microwave-Induced In Situ Amorphization of Celecoxib

Molecules ◽

10.3390/molecules26010110 ◽

2020 ◽

Vol 26 (1) ◽

pp. 110

Author(s):

Nele-Johanna Hempel ◽

Tra Dao ◽

Matthias M. Knopp ◽

Ragna Berthelsen ◽

Korbinian Löbmann

Keyword(s):

Polyethylene Glycol ◽

Microwave Radiation ◽

Magnesium Stearate ◽

Einstein Equations ◽

Dissolution Process ◽

Target Temperature ◽

Peg 4000 ◽

Lower Viscosity ◽

Model Drug

Microwaved-induced in situ amorphization of a drug in a polymer has been suggested to follow a dissolution process, with the drug dissolving into the mobile polymer at temperatures above the glass transition temperature (Tg) of the polymer. Thus, based on the Noyes–Whitney and the Stoke–Einstein equations, the temperature and the viscosity are expected to directly impact the rate and degree of drug amorphization. By investigating two different viscosity grades of polyethylene glycol (PEG), i.e., PEG 3000 and PEG 4000, and controlling the temperature of the microwave oven, it was possible to study the influence of both, temperature and viscosity, on the in situ amorphization of the model drug celecoxib (CCX) during exposure to microwave radiation. In this study, compacts containing 30 wt% CCX, 69 wt% PEG 3000 or PEG 4000 and 1 wt% lubricant (magnesium stearate) were exposed to microwave radiation at (i) a target temperature, or (ii) a target viscosity. It was found that at the target temperature, compacts containing PEG 3000 displayed a faster rate of amorphization as compared to compacts containing PEG 4000, due to the lower viscosity of PEG 3000 compared to PEG 4000. Furthermore, at the target viscosity, which was achieved by setting different temperatures for compacts containing PEG 3000 and PEG 4000, respectively, the compacts containing PEG 3000 displayed a slower rate of amorphization, due to a lower target temperature, than compacts containing PEG 4000. In conclusion, with lower viscosity of the polymer, at temperatures above its Tg, and with higher temperatures, both increasing the diffusion coefficient of the drug into the polymer, the rate of amorphization was increased allowing a faster in situ amorphization during exposure to microwave radiation. Hereby, the theory that the microwave-induced in situ amorphization process can be described as a dissolution process of the drug into the polymer, at temperatures above the Tg, is further strengthened.

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