scholarly journals Hyaluronan and Derivatives: An In Vitro Multilevel Assessment of Their Potential in Viscosupplementation

Polymers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 3208
Author(s):  
Annalisa La Gatta ◽  
Antonietta Stellavato ◽  
Valentina Vassallo ◽  
Celeste Di Meo ◽  
Giuseppe Toro ◽  
...  
Keyword(s):  
Research Work ◽  
Fold Increase ◽  
Water Soluble ◽  
Rheological Parameters ◽  
Hyaluronan Synthase ◽  
Cell Phenotype ◽  
Chemically Modified ◽  
Hydrodynamic Parameters ◽  
Hybrid Complexes

In this research work, viscosupplements based on linear, derivatized, crosslinked and complexed HA forms were extensively examined, providing data on the hydrodynamic parameters for the water-soluble-HA-fraction, rheology, sensitivity to enzymatic hydrolysis and capacity to modulate specific biomarkers’ expression in human pathological chondrocytes and synoviocytes. Soluble HA ranged from 0 to 32 mg/mL and from 150 to 1330 kDa MW. The rheological behavior spanned from purely elastic to viscoelastic, suggesting the diversity of the categories that are suitable for restoring specific/different features of the healthy synovial fluid. The rheological parameters were reduced in a diverse manner upon dilution and hyaluronidases action, indicating different durations of the viscosupplementation effect. Bioactivity was found for all the samples, increasing the expression of different matrix markers (e.g., hyaluronan-synthase); however, the hybrid cooperative complexes performed better in most of the experiments. Hybrid cooperative complexes improved COLII mRNA expression (~12-fold increase vs. CTR), proved the most effective at preserving cell phenotype. In addition, in these models, the HA samples reduced inflammation. IL-6 was down-regulated vs. CTR by linear and chemically modified HA, and especially by hybrid complexes. The results represent the first comprehensive panel of data directly comparing the diverse HA forms for intra-articular injections and provide valuable information for tailoring products’ clinical use as well as for designing new, highly performing HA-formulations that can address specific needs.

Solubility Enhancement of Poorly Water-Soluble Antifungal Drug Acyclovir by Nanocrystal Formulation Approach

2018 ◽  
Vol 11 (2) ◽  
pp. 4036-4042
Author(s):  
Prakash Goudanavar ◽  
Ankit Acharya ◽  
Vinay C.H
Keyword(s):  
Chemical Interaction ◽  
Research Work ◽  
Antiviral Drug ◽  
In Vitro Release ◽  
Oral Route ◽  
Water Soluble ◽  
Precipitation Method ◽  
Dsc Studies ◽  
Ft Ir

Administration of an antiviral drug, acyclovir via the oral route leads to low and variable bioavailability (15-30%). Therefore, this research work was aimed to enhance bioavailability of acyclovir by nanocrystallization technique. The drug nanocrystals were prepared by anti-solvent precipitation method in which different stabilizers were used. The formed nanocrystals are subjected to biopharmaceutical characterization including solubility, particle size and in-vitro release. SEM studies showed nano-crystals were crystalline nature with sharp peaks. The formulated drug nanocrystals were found to be in the range of 600-900nm and formulations NC7 and NC8 showed marked improvement in dissolution velocity when compared to pure drug, thus providing greater bioavailability. FT-IR and DSC studies revealed the absence of any chemical interaction between drug and polymers used. 

scholarly journals DESIGN, DEVELOPMENT, AND CHARACTERIZATION OF OROMUCOSAL WAFER OF TRAMADOL HYDROCHLORIDE

2018 ◽  
Vol 11 (8) ◽  
pp. 116
Author(s):  
Rita N Wadetwar ◽  
Tejaswini Charde
Keyword(s):  
Drug Release ◽  
Biodegradable Polymer ◽  
Research Work ◽  
Water Soluble ◽  
Content Uniformity ◽  
Onset Of Action ◽  
Water Soluble Polymer ◽  
Surface Ph ◽  
Folding Endurance

Objective: The objective of the present work was the preparation of fast-dissolving film of tramadol HCl (TMH) using water-soluble polymer, to achieve faster onset of action, to improve patient compliance, ease of dosing, and bypass the first-pass metabolism. Methods: TMH oromucosal wafers were prepared using pullulan as natural, biodegradable polymer, and propylene glycol as plasticizer by solvent casting method. Formulation batches were prepared using 32 full-factorial designs. The prepared TMH oromucosal wafers were characterized for morphology, uniformity of weight, drug content, folding endurance, in vitro disintegration time (DT), % moisture content, surface pH, in vitro % drug release, ex vivo permeation studies, compatibility studies (differential scanning calorimetry, Fourier transform infrared spectroscopy, and X-ray diffraction), and stability studies.Results: Optimized batch of mouth-dissolving film of TMH containing pullulan as polymer showed 98.67±0.11% drug release at 6 min. It showed better folding endurance 88 No. of folds, in vitro DT 5.11 s, surface pH 6.84±0.12 pH, thickness 0.17±0.11 mm, and percentage content uniformity 98.45±0.48%. Stability studies carried out for the best formulation FDF5 revealed that the formulation was stable.Conclusion: The results obtained in this research work clearly indicated a promising potential of fast-dissolving oral films using natural biodegradable polymer, pullulan which gave rapid drug delivery and rapid onset of action of centrally acting drug, TMH for patients suffering from pain.

scholarly journals Amorphous solid dispersions and the confounding effect of nanoparticles in in vitro dissolution and in vivo testing: Niclosamide as a case of study

2020 ◽  
Author(s):  
Miguel O Jara ◽  
Zachary N Warnken ◽  
Robert O Williams
Keyword(s):  
Amorphous Solid ◽  
Fold Increase ◽  
Water Soluble ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
In Vitro Tests ◽  
Manufacturing Method ◽  
Poorly Water Soluble

We developed an amorphous solid dispersion (ASD) of the poorly water soluble molecule niclosamide that achieved more than a 2 fold increase in bioavailability. Notably, this niclosamide ASD formulation increased the apparent drug solubility about 60 fold relative to the crystalline material due to the generation of nanoparticles. Niclosamide is a weakly acidic drug, BCS class II, and a poor glass former with low bioavailability in vivo. Hot melt extrusion is a high throughput manufacturing method commonly used in the development of ASDs for increasing the apparent solubility and bioavailability of poorly water-soluble compounds. We utilized the polymer polyvinylpyrrolidone vinyl acetate (PVPVA) to manufacture niclosamide ASDs by extrusion. Samples were analyzed based on their microscopic and macroscopic behavior and their intermolecular interactions, using DSC, XRD, NMR, FTIR, and DLS. The niclosamide ASD generated nanoparticles with a mean particle size of about 100 nm in FaSSIF media. In a side by side diffusion test, these nanoparticles produced a 4 fold increase in niclosamide diffusion. We successfully manufactured amorphous extrudates of the poor glass former niclosamide that showed remarkable in vitro dissolution and diffusion performance. These in vitro tests were translated to a rat model that also showed an increase in oral bioavailability.

scholarly journals Formulation and optimization of water soluble granules of Withania Somnifera

2021 ◽  
Vol 11 (6) ◽  
pp. 26-30
Author(s):  
Dilip Kumar Tiwari ◽  
Kaushelendra Mishra ◽  
Neelima Mishra ◽  
Neeraj Upmanyu
Keyword(s):  
Drug Release ◽  
Potential Benefit ◽  
Withania Somnifera ◽  
Research Work ◽  
Herbal Medicines ◽  
Water Extract ◽  
Water Soluble ◽  
Nootropic Activity ◽  
In Vitro Drug Release

Herbal medicines have great demand in the treatment of various kinds of illness.  Ayurvedic system of medicine has consisted of many herbal sources in which ashwagandha one of them which are the very popular herbal sources. Many literature surveys suggest that ashwagandha is used as an immunomodulator, tranquilizer, antioxidant, antidiabetic, and nootropic activity. Present research work explored the potential benefit of ashwagandha by designing suitable granules of its water extract. Further, it is characterized by various parameters and In-vitro drug release Keywords: Immunomodulator, Tranquilizers Ayurvedic, Ashwagandha, Granules

scholarly journals PHARMACOKINETIC STUDY OF MATRIX MEMBRANE MODERATED TRANSDERMAL SYSTEM OF BOSENTAN MONOHYDRATE

2017 ◽  
Vol 10 (9) ◽  
pp. 255
Author(s):  
Revathi Mannam ◽  
Indira Muzib Yallamalli
Keyword(s):  
Controlled Release ◽  
High Performance ◽  
Release Kinetics ◽  
Research Work ◽  
Fold Increase ◽  
Oral Route ◽  
Fickian Diffusion ◽  
Pharmacokinetic Studies ◽  
The Matrix

Objective: The objective of the present research work is to carry out the pharmacokinetic studies of optimized matrix membrane moderatedtransdermal patch of bosentan monohydrate.Materials and Methods: The matrix membrane moderated transdermal system was formulated using HPMC, HPMC K4M and E RLPO. In vitrodiffusion studies were carried out using modified Franz diffusion cell and for the optimized transdermal patch, pharmacokinetic studies were carriedout using New Zealand male rabbits. Plasma samples were quantified using high-performance liquid chromatography.Results: The in vitro diffusion studies revealed that formulation F3 with HPMC K4M and E RLPO had controlled release up to 28 hrs, and a maximumof 95.02±2.68% drug was released. The release kinetics followed mixed order non-Fickian diffusion. The pharmacokinetic studies of the optimizedpatch revealed controlled release up to 45 hrs where a 2.2-fold increase in area under curve (AUC) and 3.8 times increase in mean residence time(MRT) were observed compared to oral route. The results were appeared to be significant at p≤0.05. The variation in half-life was found to be notstatistically significant when compared between oral and transdermal routes.Conclusion: The pharmacokinetic results concluded that the matrix membrane moderated transdermal system with extended AUC and MRT canenhance the bioavailability of bosentan monohydrate by minimizing the drug-related side effects in oral route.

Phase 1, pharmacokinetic (PK) and pharmacodynamic (PD) study of oral alvespimycin (A; KOS-1022; 17-DMAG): Two different schedules in patients with advanced malignancies

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14059-14059 ◽  
Author(s):  
K. T. Flaherty ◽  
L. Gore ◽  
A. Avadhani ◽  
S. Leong ◽  
K. Harlacker ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Phase 1 ◽  
Fold Increase ◽  
Hsp90 Inhibitor ◽  
In Vitro Cytotoxicity ◽  
Water Soluble ◽  
Absolute Bioavailability ◽  
Post Dose ◽  
Peripheral Edema

14059 Background: A is ∼3–5 fold more potent compared to 17-AAG (the first Hsp90 inhibitor to enter clinical testing), based on in vitro cytotoxicity or the MTD in toxicology studies; it is water-soluble; and oral bioavailability in dogs is estimated at 40%. Toxicity in the dog included kidney, intestinal and liver findings. This study was conducted to determine the toxicity, MTD, recommended phase 2 dose (RP2D), PK and PD of A in pts with solid tumors. Methods: Escalating doses of A were given PO on 2 different schedules: every other day or daily for 4 out of 6 weeks. An initial IV dose was given to calculate absolute bioavailability. PK was evaluated after the IV dose, Day 1 and 21 of oral dosing. PBLs were collected to investigate changes in intracellular signaling proteins by immunoblot (Days 1 and 21 at 1, 3, 24 and 48 hours post-dose). Results: 28 pts were enrolled: 24 on the QOD schedule at doses of 5 (n=4), 10 (n=4), 20 (n=8), 30 (n=5) and 40 mg (n=3); 4 pts received 10mg on the QD schedule. 50% were male, median age/ECOG PS 55 and 0; median prior regimen 3. DLT has not yet been observed. Common drug-related toxicities (n=23): fatigue 43%, nausea 24%, anorexia 19%, proteinuria 19%, and peripheral edema 14%. Of these, fatigue and peripheral edema appear to be possibly dose-related. Drug-related Grade 3–4 toxicity (one patient each) included anemia, neutropenia, peripheral edema, hypokalemia, pain in extremity and hypoxia. For pts with full PK data (n=14), bioavailability equaled 51% and 49% on Day 1 and 21, and was not dose-dependent. Mean Day 21 AUCinf for the 5 to 30 mg/m2 levels equaled 91, 166, 542 and 1889 ng*h/mL. One pt with 3-fold increase in AUCinf comparing Day 1 and 21 dose had been started on dronabinol, a CYP2C9 inhibitor. One pt with fibrosarcoma (4 prior regimens) had necrotic changes in the tumor in the axilla with improved symptoms (active at 5+ months). Additional pts with SD include hemangioendothelioma (7 months), melanoma (6+ months), and renal cell (5 months). Induction in Hsp70 at the 30 mg dose level was seen pre-dose on Day 21 with maximal induction at 24 hours post-dose. Conclusions: Dose escalation continues on both schedules in order to define a RP2D. Toxicity is acceptable. Early signs of activity have been observed. [Table: see text]

scholarly journals Effect of Various Electrolytes on Theophylline Loaded Sodium Alginate Beads Prepared by Ionic Cross Linking Technique

2013 ◽  
Vol 11 (2) ◽  
pp. 181-189
Author(s):  
Sheikh Tasnim Jahan ◽  
Sams Mohammad Anowar Sadat ◽  
Muhammad Rashedul Islam ◽  
ATM Zafrul Azam ◽  
Jakir Ahmed Chowdhury
Keyword(s):  
Drug Release ◽  
Sodium Alginate ◽  
Electrolyte Concentration ◽  
Research Work ◽  
Three Dimensional ◽  
Alginate Beads ◽  
Water Soluble ◽  
Cross Linking ◽  
Bonding Structure

The purpose of t h e present research work was to prepare alginate beads containing water soluble drug theophylline using ionic cross linking technique, with electrolyte type and concentration as variables. In this study, the beads were characterized and evaluated in respect of their surface morphology, swelling index and in vitro kinetics. The comparative study among the three polyvalent cationic cross linking agents CaCl2 , BaCl2 and Al2 (SO4)3 were investigated based on their cationic charges. Divalent cation, Ca2+ and Ba2+ containing beads showed simultaneous decrease in drug release with increasing electrolyte amount. In case of Al3+ -alginate beads, the delay in release was due to the ability of Al3+ to form three dimensional bonding structure with the sodium alginate inside the beads. As a result, swelling of beads is delayed leading to slow disintegration. Scanning electron microscope (SEM) photomicrographs revealed that with the increase in the electrolyte concentration the density of the cross link is also increased. When the electrolyte concentration is 5 % then the beads surface is rough and rod shape drug is visible. But when the electrolyte concentration is increased from 10 % to 15 % the surface is comparatively smoother and both the swelling property and in vitro drug release are decreased. Most of the formulations followed Higuchi drug release model. DOI: http://dx.doi.org/10.3329/dujps.v11i2.14578 Dhaka Univ. J. Pharm. Sci. 11(2): 181-189, 2012 (December)

scholarly journals Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles:In VitroDrug Release and Pharmacokinetics Studies

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Praveen Kumar Gaur ◽  
Shikha Mishra ◽  
Meenakshi Bajpai ◽  
Anushika Mishra
Keyword(s):  
Drug Release ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Tween 80 ◽  
Fold Increase ◽  
Pharmacokinetic Profile ◽  
Water Soluble ◽  
Physical Parameters ◽  
Solid Lipid

Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of124.5±3.2nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment.In vitrodrug release study has shown 60.6–98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C±2°C and75±5% relative humidity (RH) for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (Cmax⁡) and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES).

Macromolecular Crowding: The Next Frontier in Tissue Engineering

2014 ◽  
Vol 96 ◽  
pp. 1-8 ◽  
Author(s):  
Pramod Kumar ◽  
Abhigyan Satyam ◽  
Diana Gaspar ◽  
Daniela Cigognini ◽  
Clara Sanz-Nogués ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Self Assembly ◽  
Macromolecular Crowding ◽  
Fold Increase ◽  
Collagen Type I ◽  
Dermal Fibroblasts ◽  
Cell Phenotype ◽  
Type I ◽  
Matrix Deposition

Tissue engineering by self-assembly hypothesises that optimal repair and regeneration can be achieved best by using the cells’ inherent ability to create organs with proficiency still unmatched by currently available scaffold fabrication technologies. However, the prolonged culture time required to develop an implantable device jeopardises clinical translation and commercialisation of such techniques. Herein, we report that macromolecular crowding, a biophysical in vitro microenvironment modulator, dramatically accelerates extracellular matrix deposition in cultured human corneal, lung and dermal fibroblasts and human bone marrow mesenchymal stem cells. In fact, an almost 5 to 30 fold increase in collagen type I deposition was recorded as early as 48 hours in culture, without any negative effect in cell phenotype and function.

scholarly journals Pharmacological Modeling and Study for Antidiabetic Activity of Praecitrullus fistulosus Leaves Extracts

2020 ◽  
Vol 10 (4-s) ◽  
pp. 13-16
Author(s):  
Ashutosh Tiwari ◽  
C.K Tyagi ◽  
Harish Pandey ◽  
Sunil Kumar Shah
Keyword(s):  
Research Work ◽  
Ethanol Extract ◽  
Extraction Methods ◽  
Water Soluble ◽  
Antidiabetic Activity ◽  
In Vivo Models ◽  
Successive Extraction ◽  
Praecitrullus Fistulosus

Phytochemical and pharmacological investigations of leaves of Praecitrullus fistulosus for the antidiabetic activity have been done in our research work encompassed in depth and systematic screening of plant leaves and further extraction, characterization and bioevaluation. The research was envisaged for antidiabetic activity of different extracts procured by successive extraction methods and to find out or isolate the most possible active compounds from the active extracts showing the best activity. The antidiabetic activity of all extracts has been evaluated by STZ induced diabetes. The isolated compounds have been evaluated by in-vitro and in-vivo models. The alcohol soluble extractives values were found to be higher than water soluble extractive value. Alcohol being a moderately non polar solvent, able to extract polar and non-polar components yields higher extractive value. The ethanol extract shows significant enhancement in glucose tolerance in glucose fed hyperglycemic normal rats and produced a marked decrease in blood glucose levels at 200 mg/kg and 400 mg/kg body weight in streptozotocin-diabetic rats after 21 days treatment. Keywords: Praecitrullus fistulosus, Streptozotocin and Glibenclamide, diabetes, Pharmacological Evaluation

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