scholarly journals Bioavailability Enhancement of Vitamin E TPGS Coated Liposomes of Nintedanib Esylate Formulation Developed Using Quality by Design Approach

2022 ◽  
Author(s):  
Shabari Girinath Kala ◽  
Santhivardhan Chinni
Keyword(s):  
Drug Release ◽  
Oral Bioavailability ◽  
High Speed ◽  
Drug Loading ◽  
Physicochemical Characterization ◽  
Amorphous State ◽  
Male Rats ◽  
Molar Ratio ◽  
Pharmacokinetic Data

Abstract PurposeNintedanib esylate (NE) is a kinase inhibitor designated for the cure of non-small cell lung cancer suffers from first-pass metabolism which resulted in low oral bioavailability (~4.7%). The intent of this exploration was to increase the oral bioavailability of NE by means of TPGS coated liposomes. MethodsThe NE-loaded TPGS coated liposomes were formulated by high-speed homogenization by optimizing process parameters like phospholipids: cholesterol molar ratio, drug loading and sonication time through the design of experiments. The drug's behaviour was studied using a variety of techniques, including physicochemical characterization, in-vitro and in-vivo studies. ResultsThe NE-liposomes had a particle size of 125±6.68 nm, entrapment efficiency of 88.64±4.12% and zeta potential of +46±2.75 mV. X-ray diffraction analysis revealed that NE had been converted to an amorphous state, while transmission electron microscope images showed spherical shape and smooth coating of TPGS on surface of liposomes. The formulation showed Higuchi kinetics with sustained drug release of 88.72 ± 3.40% in 24 hours. Cellular uptake of C-6 labelled liposomes was observed in A-549 cells and cytotoxicity testing revealed that NE-liposomes were more effective than marketed formulation Ofev®. Formulation remained in simulated fluids and for three months in stability chamber and. Liposomal oral bioavailability was ~6.23 times greater in sprague dawley male rats compared to marketed formulation Ofev®, according to in-vivo pharmacokinetic data. ConclusionNE-Liposomal formulations are better for oral administration compared to the marketed capsules because of the prolonged drug release and increased oral bioavailability as a result, the developed formulation can become a successful strategy in cancer chemotherapy.

scholarly journals Improved Bioavailability of Poorly Water-Soluble Drug by Targeting Increased Absorption through Solubility Enhancement and Precipitation Inhibition

2021 ◽  
Vol 14 (12) ◽  
pp. 1255
Author(s):  
Ju-Hyun Lee ◽  
Chulhun Park ◽  
Kwon-Yeon Weon ◽  
Chin-Yang Kang ◽  
Beom-Jin Lee ◽  
...  
Keyword(s):  
Drug Release ◽  
Amorphous State ◽  
Water Soluble ◽  
Pharmacokinetic Data ◽  
In Vivo Test ◽  
Water Soluble Drug ◽  
Absorption Area ◽  
Poorly Water Soluble

Itraconazole (ITZ) is a class II drug according to the biopharmaceutical classification system. Its solubility is pH 3-dependent, and it is poorly water-soluble. Its pKa is 3.7, which makes it a weak base drug. The aim of this study was to prepare solid dispersion (SD) pellets to enhance the release of ITZ into the gastrointestinal environment using hot-melt extrusion (HME) technology and a pelletizer. The pellets were then filled into capsules and evaluated in vitro and in vivo. The ITZ changed from a crystalline state to an amorphous state during the HME process, as determined using DSC and PXRD. In addition, its release into the gastrointestinal tract was enhanced, as was the level of ITZ recrystallization, which was lower than the marketed drug (Sporanox®), as assessed using an in vitro method. In the in vivo study that was carried out in rats, the AUC0–48h of the commercial formulation, Sporanox®, was 1073.9 ± 314.7 ng·h·mL−1, and the bioavailability of the SD pellet (2969.7 ± 720.6 ng·h·mL−1) was three-fold higher than that of Sporanox® (*** p < 0.001). The results of the in vivo test in beagle dogs revealed that the AUC0–24h of the SD-1 pellet (which was designed to enhance drug release into gastric fluids) was 3.37 ± 3.28 μg·h·mL−1 and that of the SD-2 pellet (which was designed to enhance drug release in intestinal fluids) was 7.50 ± 4.50 μg·h·mL−1. The AUC of the SD-2 pellet was 2.2 times higher than that of the SD-1 pellet. Based on pharmacokinetic data, ITZ would exist in a supersaturated state in the area of drug absorption. These results indicated that the absorption area is critical for improving the bioavailability of ITZ. Consequently, the bioavailability of ITZ could be improved by inhibiting precipitation in the absorption area.

scholarly journals Binary Solid Lipid Nanosuspension Containing Cefixime: Preparation, Characterization and Comparative In-vivo Evaluation

2019 ◽  
Author(s):  
Mahwish Kamran ◽  
Mir Azam Khan ◽  
Maqsood ur Rehman ◽  
Muhammad Shafique ◽  
Abdullah Khan ◽  
...  
Keyword(s):  
Drug Release ◽  
Oral Bioavailability ◽  
Drug Loading ◽  
Nano Particles ◽  
Pharmacokinetic Studies ◽  
Sustained Drug Release ◽  
Solid Lipid ◽  
Freeze Dried ◽  
Nano Formulation

Current study focused on resolution of poor oral bioavailability issues of cefixime through fabrication of its freeze dried binary solid lipid nano particles (SLNs). The nano formulation fabricated via hot melt encapsulation (HME) method was optimized using numerous formulation variables. Optimized nano formulation (CFX-4) showed particle size 206.6±2.3 nm, polydispersity index (PDI) 0.271±0.03, zeta potential (ZP) -30.7±3.1 mV, encapsulation efficiency (EE%) 88.2±2.3% along with drug loading capacity (DLC%) 4.83±0.16%. Micrograph of scanning electron microscopy (SEM) represented spherical shaped particles. Reduction in drug’s crystalline nature was acknowledged through differential scanning calorimetry (DSC) and x-ray powder diffraction (P-XRD) analysis. Drug-excepient compatibility was established through fourier transform infrared spectroscopic (FT-IR) analysis. During in-vitro studies; sustained drug release was favored by increased drug payload. Stability studies exposed that refrigerated temperature imparts maximum stability to binary SLNs. In-vivo pharmacokinetic studies revealed the desired enhancement in oral bioavailability compared to the marketed product (Cefiget®). Presented investigations established the dominance of binary SLNs for improvement of oral bioavailability with sustained drug release characteristics. Based on the reported outcomes, binary SLNs can be employed as an advanced drug delivery system for other hydrophobic drugs.

Enhanced oral bioavailability of nisoldipine-piperine-loaded poly-lactic-co-glycolic acid nanoparticles

2017 ◽  
Vol 6 (6) ◽  
pp. 517-526 ◽  
Author(s):  
Permender Rathee ◽  
Anjoo Kamboj ◽  
Shabir Sidhu
Keyword(s):  
Oral Bioavailability ◽  
Drug Loading ◽  
Average Particle Size ◽  
Entrapment Efficiency ◽  
Pharmacokinetic Interaction ◽  
Precipitation Method ◽  
Pharmacokinetic Studies ◽  
Average Particle

AbstractBackground:Piperine helps in the improvement of bioavailability through pharmacokinetic interaction by modulating metabolism when administered with other drugs. Nisoldipine is a substrate for cytochrome P4503A4 enzymes. The study was undertaken to assess the influence of piperine on the pharmacokinetics and pharmacodynamics of nisoldipine nanoparticles in rats.Methods:Optimization studies of nanoparticles were performed using Taguchi L9 orthogonal array, and the nanoparticles were formulated by the precipitation method. The influence of piperine and nanoparticles was evaluated by means of in vivo kinetic and dynamic studies by oral administration in rats.Results:The entrapment efficiency, drug loading, ζ potential, and average particle size of optimized nisoldipine-piperine nanoparticles was 89.77±1.06%, 13.6±0.56%, −26.5 mV, and 132±7.21 nm, respectively. The in vitro release in 0.1 n HCl and 6.8 pH phosphate buffer was 96.9±0.48% and 98.3±0.26%, respectively. Pharmacokinetic studies showed a 4.9-fold increase in oral bioavailability and a >28.376±1.32% reduction in systemic blood pressure by using nanoparticles as compared to control (nisoldipine suspension) in Wistar rats.Conclusion:The results revealed that piperine being an inhibitor of cytochrome P4503A4 enzymes enhanced the bioavailability of nisoldipine by 4.9-fold in nanoparticles.

scholarly journals Novel Gliclazide Electrosprayed Nano-Solid Dispersions: Physicochemical Characterization and Dissolution Evaluation

2019 ◽  
Vol 9 (2) ◽  
pp. 231-240
Author(s):  
Khosro Adibkia ◽  
Solmaz Ghajar ◽  
Karim Osouli-Bostanabad ◽  
Niloufar Balaei ◽  
Shahram Emami ◽  
...  
Keyword(s):  
Drug Release ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Physicochemical Characterization ◽  
Amorphous State ◽  
Water Soluble ◽  
Fickian Diffusion ◽  
Release Mechanism ◽  
Peg 6000

Purpose: In the current study, electrospraying was directed as a novel alternative approach to improve the physicochemical attributes of gliclazide (GLC), as a poorly water-soluble drug, by creating nanocrystalline/amorphous solid dispersions (ESSs). Methods: ESSs were formulated using Eudragit® RS100 and polyethylene glycol (PEG) 6000 as polymeric carriers at various drug: polymer ratios (i.e. 1:5 and 1:10) with different total solution concentrations of 10, 15, and 20% w/v. Morphological, physicochemical, and in-vitro release characteristics of the developed formulations were assessed. Furthermore, GLC dissolution behaviors from ESSs were fitted to various models in order to realize the drug release mechanism. Results: Field emission scanning electron microscopy analyses revealed that the size and morphology of the ESSs were affected by the drug: polymer ratios and solution concentrations. The polymer ratio augmentation led to increase in the particle size while the solution concentration enhancement yielded in a fiber establishment. Differential scanning calorimetry and powder X-ray diffraction investigations demonstrated that the ESSs were present in an amorphous state. Furthermore, the in vitro drug release studies depicted that the samples prepared employing PEG 6000 as carrier enhanced the dissolution rate and the model that appropriately fitted the release behavior of ESSs was Weibull model, where demonstrating a Fickian diffusion as the leading release mechanism. Fourier-transform infrared spectroscopy results showed a probability of complexation or hydrogen bonding, development between GLC and the polymers in the solid state. Conclusion: Hence the electrospraying system avails the both nanosizing and amorphization advantages, therefore, it can be efficiently applied to formulating of ESSs of BCS Class II drugs.

scholarly journals Formulation, Development and Evaluation of Ibuprofen Loaded Nano-transferosomal Gel for the Treatment of Psoriasis

2019 ◽  
pp. 1-8
Author(s):  
Marwa H. Abdallah ◽  
Amr S. Abu Lila ◽  
Md. Khalid Anwer ◽  
El-Sayed Khafagy ◽  
Muqtader Mohammad ◽  
...  
Keyword(s):  
Drug Release ◽  
Zeta Potential ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Tween 80 ◽  
Formulation Development ◽  
In Vitro Drug Release ◽  
Vesicle Size

The present work was aimed to develop a transferosomal gel of ibuprofen (IBU) for the amelioration of psoriasis like inflammation. Three formulation of IBU loaded transferosomes (TFs1-TFs3) were prepared using different proportions of lipid (phospholipon 90H) and surfactant (tween 80) and further evaluated for vesicle size, zeta potential (ZP), entrapment efficiency and in vitro drug release. The IBU loaded transferosomes (TFs2) was optimized with vesicle size (217±8.4 nm), PDI (0.102), ZP (-31.5±4.3 mV), entrapment efficiency (88.4±6.9%) and drug loading (44.2±2.9%). Further, the optimized IBU loaded transferosomes (TFs2) was incorporated into 1% carbopol 934 gel base and characterized for homogeneity, extrudability, viscosity and drug content. The in vivo pharmacodynamic study of gel exhibited reduction in psoriasis like inflammation in mice. The ibuprofen loaded transferosomal gel was successfully developed and has shown the potential to be a new therapy against psoriasis like inflammation.

scholarly journals Considerable Improvement of Ursolic Acid Water Solubility by Its Encapsulation in Dendrimer Nanoparticles: Design, Synthesis and Physicochemical Characterization

Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2196 ◽  
Author(s):  
Silvana Alfei ◽  
Anna Maria Schito ◽  
Guendalina Zuccari
Keyword(s):  
Ursolic Acid ◽  
Water Solubility ◽  
Drug Loading ◽  
Physicochemical Characterization ◽  
Systemic Toxicity ◽  
Water Soluble ◽  
Design Synthesis ◽  
Pentacyclic Triterpenoid

Ursolic acid (UA) is a pentacyclic triterpenoid found in many medicinal plants and aromas endowed with numerous in vitro pharmacological activities, including antibacterial effects. Unfortunately, UA is poorly administered in vivo, due to its water insolubility, low bioavailability, and residual systemic toxicity, thus making urgent the development of water-soluble UA formulations. Dendrimers are nonpareil macromolecules possessing highly controlled size, shape, and architecture. In dendrimers with cationic surface, the contemporary presence of inner cavities and of hydrophilic peripheral functions, allows to encapsulate hydrophobic non-water-soluble drugs as UA, to enhance their water-solubility and stability, and to promote their protracted release, thus decreasing their systemic toxicity. In this paper, aiming at developing a new UA-based antibacterial agent administrable in vivo, we reported the physical entrapment of UA in a biodegradable not cytotoxic cationic dendrimer (G4K). UA-loaded dendrimer nanoparticles (UA-G4K) were obtained, which showed a drug loading (DL%) much higher than those previously reported, a protracted release profile governed by diffusion mechanisms, and no cytotoxicity. Also, UA-G4K was characterized by principal components analysis (PCA)-processed FTIR spectroscopy, by NMR and elemental analyses, and by dynamic light scattering experiments (DLS). The water solubility of UA-G4K was found to be 1868-fold times higher than that of pristine UA, thus making its clinical application feasible.

A Smart Drug Delivery System Based on Thermo-Responsive Polymer Gated Au NRs@SiO2 Nano-Platform

2021 ◽  
Vol 16 (7) ◽  
pp. 1029-1036
Author(s):  
Hongzhu Wang ◽  
Mengxun Chen ◽  
Liping Song ◽  
Youju Huang
Keyword(s):  
Drug Delivery ◽  
Block Copolymer ◽  
Drug Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Photothermal Therapy ◽  
Drug Loading ◽  
Temperature Sensitive

A key challenge for nanoparticles-based drug delivery system is to achieve manageable drug release in tumour cell. In this study, a versatile system combining photothermal therapy and controllable drug release for tumour cells using temperature-sensitive block copolymer coupled Au NRs@SiO2 is reported. While the Au NRs serve as hyperthermal agent and the mesoporous silica was used to improve the drug loading and decrease biotoxicity. The block copolymer acted as “gatekeeper” to regulate the release of model drug (Doxorubicin hydrochloride, DOX). Through in vivo and in vitro experiments, we achieved the truly controllable drug release and photothermal therapy with the collaborative effect of the three constituents of the nanocomposites. The reported nanocomposites pave the way to high-performance controllable drug release and photothermal therapy system.

Development and Characterization of Binary Solid Lipid Nano Suspension of Atorvastatin: In-Vitro Drug Release and In-Vivo Pharmacokinetic Studies

2019 ◽  
Vol 11 (11) ◽  
pp. 1522-1530
Author(s):  
Mahwish Kamran ◽  
Mir Azam Khan ◽  
Muhammad Shafique ◽  
Maqsood ur Rehman ◽  
Waqar Ahmed ◽  
...  
Keyword(s):  
Drug Release ◽  
Oral Bioavailability ◽  
Drug Loading ◽  
Lipid Lowering ◽  
Diffusion Method ◽  
Pharmacokinetic Studies ◽  
Drug Release Profile ◽  
Sustained Drug Release ◽  
Solid Lipid

Atorvastatin is an extensively used lipid lowering agent. But the vital issue associated with it is low oral bioavailability (12%) owing to poor aqueous solubility. To overcome this tribulation, binary solid lipid nano suspension of Atorvastatin (ATO) was formulated by solvent diffusion method. The combination of stearic acid and oleic acid was utilized as a lipid carrier with Tween-80 (surfactant) along with Polyvinylpyrrolidone (co-surfactant). Optimized nano formulation was prepared by changing the formulation variables. Optimized nano suspension (ATO-4) represented particle size 228.3 ± 2.1 nm and polydispersity index (PDI) 0.225 ± 0.02 with zeta potential (ZP) – 33.6 ± 0.02 mV. Encapsulation efficiency along with drug loading capacity was 88.3 ± 2.5% and 4.9 ± 0.14% respectively. Scanning electron microscopic (SEM) analysis exposed spherical shaped amorphous particles. Differential scanning calorimetry (DSC) as well as X-ray powder diffraction (P-XRD) established reduction in drug's crystalline state. Fourier transform infrared (FTIR) spectroscopy exposed no interaction amongst the drug and formulation contents. In-vitro studies revealed sustained pattern of drug release. Stability studies confirmed refrigerated temperature as most suitable for storage of binary solid lipid nano suspension. Plasma concentration versus time curve ascertained 2.78-fold increase in oral bioavailability of ATO nano suspension compared to the marketed product (Lipitor®). Findings proposed desired improvement in oral bioavailability of ATO nano suspension with sustained drug release profile. Thus, binary solid lipid nano suspension could be utilized as an advanced drug delivery system for oral deliverance of hydrophobic drugs.

scholarly journals PREPARATION AND CHARACTERIZATION OF ORAL NANOSUSPENSION LOADED WITH CURCUMIN

2018 ◽  
Vol 10 (6) ◽  
pp. 90 ◽  
Author(s):  
Sneha Dekate Shreeram Hirlekar ◽  
Srinivas Bhairy ◽  
Srinivas Bhairy ◽  
Rajashree Hirlekar ◽  
Rajashree Hirlekar
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
High Speed ◽  
Drug Loading ◽  
Research Work ◽  
Release Kinetic ◽  
Pharmacokinetic Studies ◽  
Sprague Dawley ◽  
Saturation Solubility

Objective: The principle objective of the present research work was to improve the bioavailability of curcumin (CUR) by decreasing its particle size. Nanosuspension (NS) of CUR was prepared using poloxamer-188 (P188) as a surfactant. The prepared NSs were characterized for particle size, polydispersity index (PDI), zeta potential, drug loading, saturation solubility, and drug release kinetic studies.Methods: Components required for NS preparation, such as solvent, anti-solvent and surfactant were screened. Precipitation high-speed homogenization (HSH) method was used for the preparation of NS using selected components. Evaluation of NS for particle size, PDI, drug loading, saturation solubility and in vitro drug release was done. Pharmacokinetic studies of the NS in sprague dawley (SD) rats were performed.Results: The particle size, PDI and zeta potential of the optimized formulation was 596.5±5 nm, 0.233±0.010 and-23±2 mV respectively. The pH of all the formulations was in the range of 5-6 which is acceptable when related to drug stability. The optimized formulation showed an increase in saturation solubility in water and phosphate buffer pH 6.8 when compared to plain CUR suspension (S). Results of pharmacokinetic studies indicated that Cmax and AUC0-6 were increased 8 and 10 times respectively from plain CUR S to CUR NS.Conclusion: CUR NS was prepared using P188 as the stabilizer. Amongst various stabilizers screened P188 rendered a stable NS with the particle size in nano range. Pharmacokinetic studies revealed the better performance of CUR NS as compared to plain CUR S.

NANOMEDICINES: DELIVERING DRUGS USING BOTTOM UP NANOTECHNOLOGY

2005 ◽  
Vol 04 (05n06) ◽  
pp. 855-861 ◽  
Author(s):  
MARTIN GARNETT
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Biodegradable Polymers ◽  
Drug Loading ◽  
Dna Delivery ◽  
Delivery Systems ◽  
The Body ◽  
Nanosized Materials

The use of nanosized materials changes the way in which drugs are handled by the body and offers opportunities to improve drug delivery. The physiological mechanisms controlling the distribution of nanosized materials (enhanced permeability and retention effect, cellular uptake pathways and opsonisation/elimination of nanoparticles) are described. Two different nanosized drug delivery systems are considered; drug delivery and DNA delivery. The deficiencies of currently available biodegradable polymers for preparation of drug containing nanoparticles are mainly the amount of drug that can be incorporated and the rapid rate of drug release. The development of new biodegradable polymers which can interact with the drug and so significantly increase drug loading and decrease the rate of drug release are outlined. DNA delivery necessitates overcoming a variety of biological barriers. We are developing polyelectrolyte complexes of DNA with cationic polyamidoamines (PAA) as a delivery system. Complexing PAA with DNA results in good transfection of cells in vitro. However, in vivo, a more complex arrangement of PAA, Polyethylene glycol-PAA copolymers, DNA and the use of ligands will be required. Despite these efforts, further developments will be needed in nanotechnology for both drug and DNA nanoparticle delivery systems to achieve our clinical objectives.

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