scholarly journals Niclosamide–Clay Intercalate Coated with Nonionic Polymer for Enhanced Bioavailability toward COVID-19 Treatment

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1044
Author(s):  
Seungjin Yu ◽  
Huiyan Piao ◽  
N. Sanoj Rejinold ◽  
Geunwoo Jin ◽  
Goeun Choi ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Interlayer Space ◽  
Systemic Exposure ◽  
Aqueous Solubility ◽  
Drug Formulation ◽  
Nonionic Polymer ◽  
Enhanced Solubility ◽  
Tween 60 ◽  
Polymer Surfactant

Niclosamide (NIC), a conventional anthelmintic agent, is emerging as a repurposed drug for COVID-19 treatment. However, the clinical efficacy is very limited due to its low oral bioavailability resulting from its poor aqueous solubility. In the present study, a new hybrid drug delivery system made of NIC, montmorillonite (MMT), and Tween 60 is proposed to overcome this obstacle. At first, NIC molecules were immobilized into the interlayer space of cationic clay, MMT, to form NIC–MMT hybrids, which could enhance the solubility of NIC, and then the polymer surfactant, Tween 60, was further coated on the external surface of NIC–MMT to improve the release rate and the solubility of NIC and eventually the bioavailability under gastrointestinal condition when orally administered. Finally, we have performed an in vivo pharmacokinetic study to compare the oral bioavailability of NIC for the Tween 60-coated NIC–MMT hybrid with Yomesan®, which is a commercially available NIC. Exceptionally, the Tween 60-coated NIC–MMT hybrid showed higher systemic exposure of NIC than Yomesan®. Therefore, the present NIC–MMT–Tween 60 hybrid can be a potent NIC drug formulation with enhanced solubility and bioavailability in vivo for treating Covid-19.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

scholarly journals PREPARATION AND CHARACTERIZATION OF NANOCRYSTALS FOR SOLUBILITY AND DISSOLUTION RATE ENHANCEMENT OF PALIPERIDONE USING DIFFERENT HYDROPHILIC CARRIERS: IN VITRO-IN VIVO STUDY

2018 ◽  
Vol 11 (4) ◽  
pp. 393
Author(s):  
Moon Rajkumar ◽  
Gattani Surendra
Keyword(s):  
Dissolution Rate ◽  
Antipsychotic Agent ◽  
Aqueous Solubility ◽  
In Vivo Study ◽  
Scanning Calorimetry ◽  
Antisolvent Precipitation ◽  
Enhanced Solubility ◽  
Pure Drug

 Objective: The objective of this study was to increase the solubility and dissolution rate of paliperidone (PAL) by preparing its nanocrystals using different hydrophilic carriers by antisolvent precipitation technique.Methods: The nanoparticles (NP) were characterized for aqueous solubility, drug content, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, particle size, and in vitro-in vivo analysis.Results: The results showed improved solubility and dissolution rate of NPs when compared to pure drug and physical mixture (PM). Solubility data showed a linear graph giving an indication that there is a gradual increase in the solubility profile of the drug with an increase in concentration of the carriers. At highest concentration, the solubility of NPs with Plasdone S630, Povidone K-25, and PVP K-30 found to be increased by 12 folds, 9 folds and 6 folds, respectively, as compared to pure drug. The release profile of NPs with Plasdone S630 in terms of dissolution efficiency at 60 min (DE60), initial dissolution rate (IDR), amount release in 15 min (Q15 min), and time for 75% release (t75%) shows better results when compared to pure drug, PM, and also NPs with povidone 25 and povidone 30. In vivo study reveals that optimized NPs elicited significant induction of cataleptic behavior which is the indication of antipsychotic agent(s) effect.Conclusion: The process antisolvent precipitation under constant stirring may be a promising method to produce stable PAL NPs with markedly enhanced solubility and dissolution rate due to nanonization with the increased surface area, improved wettability, and reduced diffusion pathway.

scholarly journals Development of a Ternary Solid Dispersion Formulation of LW6 to Improve the In Vivo Activity as a BCRP Inhibitor: Preparation and In Vitro/In Vivo Characterization

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 206 ◽  
Author(s):  
Rajiv Bajracharya ◽  
Sang Hoon Lee ◽  
Jae Geun Song ◽  
Minkyoung Kim ◽  
Kyeong Lee ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous State ◽  
Weight Ratio ◽  
Acid Methyl Ester ◽  
Systemic Exposure ◽  
Aqueous Solubility ◽  
Poloxamer 407 ◽  
Cancer Resistance ◽  
Ternary Solid Dispersion

LW6 (3-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-4-hydroxy-benzoic acid methyl ester) is a potent inhibitor of drug efflux by the breast cancer resistance protein (BCRP). However, its poor aqueous solubility leads to low bioavailability, which currently limits in vivo applications. Therefore, the present study aimed to develop ternary solid dispersion (SD) formulations in order to enhance the aqueous solubility and dissolution rate of LW6. Various SDs of LW6 were prepared using a solvent evaporation method with different drug/excipient ratios. The solubility and dissolution profiles of LW6 in different SDs were examined, and F8-SD which is composed of LW6, poloxamer 407, and povidone K30 at a weight ratio of 1:5:8 was selected as the optimal SD. The structural characteristics of F8-SD were also examined using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM). In the acidic to neutral pH range, F8-SD achieved rapid dissolution with a drug release of 76–81% within 20 min, while the dissolution of pure LW6 was negligible. The XRPD patterns indicated that F8-SD probably enhanced the solubility and dissolution of LW6 by changing the drug crystallinity to an amorphous state, in addition to the solubilizing effect of the hydrophilic carriers. Furthermore, F8-SD significantly improved the oral bioavailability of topotecan, which is a BCRP substrate, in rats. The systemic exposure of topotecan was enhanced approximately 10-fold by the concurrent use of F8-SD. In conclusion, the ternary SD formulation of LW6 with povidone K30 and poloxamer 407 appeared to be effective at improving the dissolution and in vivo effects of LW6 as a BCRP inhibitor.

Enhanced Oral Bioavailability and Improved Biological Activities of a Quercetin/Resveratrol Combination Using a Liquid Self-Microemulsifying Drug Delivery System

Planta Medica ◽  
2020 ◽  
Author(s):  
Patcharawalai Jaisamut ◽  
Subhaphorn Wanna ◽  
Surasak Limsuwan ◽  
Sasitorn Chusri ◽  
Kamonthip Wiwattanawongsa ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Oral Bioavailability ◽  
Biological Activities ◽  
Area Under The Curve ◽  
Aqueous Solubility ◽  
The Self

AbstractBoth quercetin and resveratrol are promising plant-derived compounds with various well-described biological activities; however, they are categorized as having low aqueous solubility and labile natural compounds. The purpose of the present study was to propose a drug delivery system to enhance the oral bioavailability of combined quercetin and resveratrol. The suitable self-microemulsifying formulation containing quercetin together with resveratrol comprised 100 mg Capryol 90, 700 mg Cremophor EL, 200 mg Labrasol, 20 mg quercetin, and 20 mg resveratrol, which gave a particle size of 16.91 ± 0.08 nm and was stable under both intermediate and accelerated storage conditions for 12 months. The percentages of release for quercetin and resveratrol in the self-microemulsifying formulation were 75.88 ± 1.44 and 86.32 ± 2.32%, respectively, at 30 min. In rats, an in vivo pharmacokinetics study revealed that the area under the curve of the self-microemulsifying formulation containing quercetin and resveratrol increased approximately ninefold for quercetin and threefold for resveratrol compared with the unformulated compounds. Moreover, the self-microemulsifying formulation containing quercetin and resveratrol slightly enhanced the in vitro antioxidant and cytotoxic effects on AGS, Caco-2, and HT-29 cells. These findings demonstrate that the self-microemulsifying formulation containing quercetin and resveratrol could successfully enhance the oral bioavailability of the combination of quercetin and resveratrol without interfering with their biological activities. These results provide valuable information for more in-depth research into the utilization of combined quercetin and resveratrol.

scholarly journals DEVELOPMENT OF SELF NANO-EMULSIFYING DRUG DELIVERY SYSTEM FOR AN ANTI-HYPERTENSIVE AGENT FELODIPINE: A SYSTEMATIC APPROACH FOR LIPID NANO-FORMULATION WITH IMPROVED ORAL BIOAVAILABILITY IN RATS

2020 ◽  
pp. 86-94
Author(s):  
K. TRIDEVA SASTRI ◽  
G. V. RADHA
Keyword(s):  
Droplet Size ◽  
Aqueous Solubility ◽  
Bioavailability Enhancement ◽  
Cinnamon Oil ◽  
Stability Robustness ◽  
Tween 60 ◽  
Spherical Droplets ◽  
Nano Formulation

Objective: The present study involves the development of SNEDDS employing essential oils for enhancing biopharmaceutical performance. Methods: Preliminary investigations suggested the selection of cinnamon oil as an essential oil, tween 60 as a surfactant, while transcutol HP as a cosolvent for formulating SNEDDS. Formulations evaluated for stability, robustness to dilution, and emulsification time, droplet size, zeta potential (ζ), cloud point, in vitro drug release, drug excipient compatibility, TEM, stability assessment and in vivo pharmacokinetic performance in rats. Results: All formulations were robust, stable, and revealed excellent emulsification time<40 s, with fine droplet size (11.41±2.41 nm), lower PDI (0.028-0.277). Formulation F(FLD)6 exhibited a release of 97.7% within 4h, and TEM photograph confirmed spherical droplets. The bioavailability results revealed a higher rate and extent of absorption, AUC, and Cmax for the formulations found to be 1212.4 and 355.40±13.67 (p<0.05). The results recommend that the developed formulation approach offers bioavailability enhancement of FLD. Conclusion: The study concluded that SNEDDS would be an effective formulation system in increasing the aqueous solubility and potentially bioavailability. Furthermore, it can be applied for other therapeutic categories of drugs belonging to BCS class II and IV that show comparable biopharmaceutical challenges.

In Vitro and In Vivo Evaluation of Olmesartan Medoxomil Microcrystals and Nanocrystals: Preparation, Characterization, and Pharmacokinetic Comparison in Beagle Dogs

2019 ◽  
Vol 16 (6) ◽  
pp. 500-510
Author(s):  
Rong Chai ◽  
Hailing Gao ◽  
Zhihui Ma ◽  
Meng Guo ◽  
Qiang Fu ◽  
...  
Keyword(s):  
Particle Size ◽  
Oral Bioavailability ◽  
Olmesartan Medoxomil ◽  
Water Soluble ◽  
Size Reduction ◽  
Drug Dissolution ◽  
Beagle Dogs ◽  
Enhanced Solubility

Background: Olmesartan medoxomil (OLM) is a promising prodrug hydrolyzed to olmesartan (OL) during absorption from the gastrointestinal tract. OL is a selective angiotensin II receptor antagonist, with high drug resistance and low drug interaction. However, OLM has low solubility and low bioavailability. Therefore, it is extremely urgent to reduce the drug particle size to improve its biological bioavailability. Objective: The aim of the study was to improve the oral bioavailability of poorly water-soluble olmesartan medoxomil (OLM) by using different particle size-reduction strategies. Method: Raw drug material was micronized or nanosized by either jet or wet milling processes, respectively. The particle sizes of the prepared nanocrystals (100-300 nm) and microcrystals (0.5-16 μm) were characterized by DLS, SEM, and TEM techniques. Solid state characterization by XPRD and DSC was used to confirm the crystalline state of OLM after the milling processes. Results: We demonstrated that OLM nanocrystals enhanced solubility and dissolution in the non-sink condition in which high sensitivity was found in purified water. After 1 h, 65.4% of OLM was dissolved from nanocrystals, while microcrystals and OLMETEC® only showed 37.8% and 31.9% of drug dissolution, respectively. In the pharmacokinetic study using Beagle dogs, an increase in Cmax (～2 fold) and AUC (～1.6 fold) was observed after oral administration of OLM nanocrystals when compared to microcrystals and reference tablets, OLMETEC®. In contrast, OLM microcrystals failed to improve the oral bioavailability of the drugs. Conclusion: Particles size reduction to nano-scale by means of nanocrystals technology significantly increased in vitro dissolution rate and in vivo oral bioavailability of OLM.

The effect of nanonization on poorly water soluble glibenclamide using a liquid anti-solvent precipitation technique: aqueous solubility, in vitro and in vivo study

RSC Advances ◽  
2015 ◽  
Vol 5 (99) ◽  
pp. 81728-81738 ◽  
Author(s):  
Rohan D. Deshpande ◽  
Gowda D. V. ◽  
Naga Sravan Kumar Varma Vegesna ◽  
Rudra Vaghela ◽  
Kulkarni P. K.
Keyword(s):  
Process Parameters ◽  
Oral Bioavailability ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
In Vivo Study ◽  
Precipitation Technique ◽  
Poorly Water Soluble

In the present study, efforts were made to optimize the process parameters of LAS technique for developing GLB NPs, in order to enhance the aqueous solubility as well as oral bioavailability.

Lutein encapsulated oleic - linoleic acid nanoemulsion boosts oral bioavailability of retinal protective carotenoid lutein in rat model

2021 ◽  
Author(s):  
Veeresh B Toragall ◽  
Twinkle Godhwani ◽  
V Baskaran ◽  
Naveen Jayapala
Keyword(s):  
Linoleic Acid ◽  
Oral Bioavailability ◽  
Mixed Micelles ◽  
Water Solubility ◽  
Health Benefits ◽  
Aqueous Solubility ◽  
Mean Size ◽  
The Mean

Abstract There is excessive interest in emerging colloidal delivery systems to enhance the water solubility and oral bioavailability of lutein, which is a hydrophobic carotenoid claimed to possess health benefits. The present study aimed to design lutein-enriched nanoemulsions with improved physicochemical properties and to achieve various health benefits of lutein. The prepared lutein nanoemulsion was characterized, and its bioavailability was examined in vitro (simulated gastrointestinal digestion) and in vivo. The mean size, PDI and zeta potential of the lutein nanoemulsion were 110 ± 8 nm, 0.271 and 36 ± 2 mV, respectively. Furthermore, TEM examination revealed that the particles are nanosized and spherical in shape. Notably, the aqueous solubility of the nanoemulsion was 726-fold higher than that of free lutein. The composite nanoemulsion also showed exceptionally higher (87.4%) in vitro bioaccessibility than that of nonencapsulated or free lutein (15%). The in vivo bioavailability of lutein nanoemulsion (112.6 ng/mL) was much higher than that of nonencapsulated lutein (48.6 ng/ml) and mixed micelles (68.5 ng/mL), and the tissue distribution pattern of lutein nanoemulsion showed higher lutein accumulation in the liver (2.80- and 1.70-fold) and eye (1.91- and 1.48-fold) compared to free lutein and mixed micelle-fed groups. These results suggested that oleic acid-linoleic acid composite nanoemulsions may be a promising delivery system for lutein and may help enhance the solubility, oral bioavailability and bioefficacy of lutein and could be used as an ingredient for the formulation of beverages or functional foods.

scholarly journals Precise Dissolution Control and Bioavailability Evaluation for Insoluble Drug Berberine via a Polymeric Particle Prepared Using Supercritical CO2

Polymers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1198 ◽  
Author(s):  
Jingfu Jia ◽  
Kerong Zhang ◽  
Xue Zhou ◽  
Dan Zhou ◽  
Fahuan Ge
Keyword(s):  
Oral Bioavailability ◽  
Supercritical Co2 ◽  
Pharmaceutical Research ◽  
Particle Morphology ◽  
Aqueous Solubility ◽  
Dissolution Enhancement ◽  
Resonance Spectroscopy ◽  
Pharmacokinetic Studies ◽  
Scanning Calorimetry

It is still controversial whether poor aqueous solubility is the most primary reason for the low oral bioavailability of insoluble drugs. Therefore, in this study, berberine-loaded solid polymeric particles (BPs) of varied dissolution profiles with β-cyclodextrin (β-CD) as carrier were fabricated using solution-enhanced dispersion by supercritical fluids (SEDS), and the relationship between dissolution and berberine (BBR) bioavailability was evaluated. Dissolution property was controlled via particle morphology manipulation, which was achieved by adjusting several key operating parameters during the SEDS process. Characterization on BP using infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction indicated that BBR was dispersed in amorphous form, while nuclear magnetic resonance spectroscopy showed that methoxy groups of BBR were included into the cavities of β-CD. In vivo pharmacokinetic studies showed that oral bioavailability increased by about 54% and 86% when the dissolution rate of BBR was increased by 51% and 83%, respectively. The entry speed of BBR into the bloodstream was also advanced with the degree of dissolution enhancement. It seemed that dissolution enhancement gave positive effect to the oral bioavailability of berberine, but this might not be the crucial point. Meanwhile, supercritical CO2 technology is a promising method for pharmaceutical research due to its advantages in regulating drug-dosage properties.

scholarly journals Improved antimalarial activity of caprol-based nanostructured lipid carriers encapsulating artemether-lumefantrine for oral administration

2020 ◽  
Vol 20 (4) ◽  
pp. 1679-97
Author(s):  
Paul Achile Akpa ◽  
Joseph Abuchi Ugwuoke ◽  
Anthony Amaechi Attama ◽  
Chinenye Nnenna Ugwu ◽  
Ezinwanne Nneoma Ezeibe ◽  
...  
Keyword(s):  
Oral Bioavailability ◽  
Antimalarial Activity ◽  
Aqueous Solubility ◽  
Organ Damage ◽  
Nanostructured Lipid Carriers ◽  
Release Formulation ◽  
Sustained Release Formulation ◽  
Logical Investigations ◽  
Histopathological Studies

Background: Artemether and lumefantrine display low aqueous solubility leading to poor release profile; hence the need for the use of lipid-based systems to improve their oral bioavailability so as to improve their therapeutic efficacy. Aim and objective: The objective of this work was to utilize potentials of nanostructured lipid carriers (NLCs) for im- provement of the oral bioavailability of artemether and lumefantrine combination and to evaluate its efficacy in the treat- ment of malaria. This study reports a method of formulation, characterization and evaluation of the therapeutic efficacies of caprol-based NLC delivery systems with artemether and lumefantrine. Method: The artemether-lumefantrine co-loaded NLCs were prepared using the lipid matrix (5% w/w) (containing beeswax and Phospholipon® 90H and Caprol-PGE 860), artemether (0.1%w/w) and lumefantrine (0.6%w/w), sorbitol (4%w/w), Tween® 80( 2%w/was surfactant) and distilled water (q.s to 100%) by high shear homogenization and evaluated for phys- icochemical performance. The in vivo antimalarial activities of the NLC were tested in chloroquine-sensitive strains of Plasmodium berghei (NK-65) using Peter´s 4-day suppressive protocol in mice and compared with controls. Histopathological studies were also carried out on major organs implicated in malaria. Results: The NLC showed fairly polydispersed nano-sized formulation (z-average:188.6 nm; polydispersity index, PDI=0.462) with no major interaction occurring between the components while the in vivo study showed a gradual but sus- tained drug release from the NLC compared with that seen with chloroquine sulphate and Coartem®. Results of histopatho- logical investigations also revealed more organ damage with the untreated groups than groups treated with the formulations. Conclusion: This study has shown the potential of caprol-based NLCs for significant improvement in oral bioavailability and hence antimalarial activity of poorly soluble artemether and lumefantrine. Importantly, this would improve patient com- pliance due to decrease in dosing frequency as a sustained release formulation. Keywords: Nanostructured lipid carriers; artemether-lumefantrine; malaria; Caprol.

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