scholarly journals Improving the Solubilization and Bioavailability of Arbidol Hydrochloride by the Preparation of Binary and Ternary β-Cyclodextrin Complexes with Poloxamer 188

2021 ◽  
Vol 14 (5) ◽  
pp. 411
Author(s):  
Md. Khalid Anwer ◽  
Muzaffar Iqbal ◽  
Mohammad Muqtader Ahmed ◽  
Mohammed F. Aldawsari ◽  
Mohd Nazam Ansari ◽  
...  
Keyword(s):  
Antiviral Agent ◽  
Aqueous Solubility ◽  
Phase Solubility ◽  
Pharmacokinetic Studies ◽  
Solubility Curve ◽  
Cyclodextrin Complexes ◽  
Poloxamer 188 ◽  
The Stability

In the current study, the effect of poloxamer 188 on the complexation efficiency and dissolution of arbidol hydrochloride (ADL), a broad-spectrum antiviral agent, with β-cyclodextrin (β-CD) was investigated. Phase solubility studies confirmed a stoichiometry of a 1:1 ratio for both ADL:β-CD and ADL/β-CD with a 1% poloxamer 188 system with an AL type of phase solubility curve. The stability constants (K1:1) calculated from the AL type diagram were 550 M-1 and 2134 M-1 for AD:β-CD and ADL/β-CD with 1% poloxamer 188, respectively. The binary ADL/β-CD and ternary ADL/β-CD with 1% poloxamer 188 complexes were prepared by kneading and a solvent evaporation method and were characterized by aqueous solubility, FTIR, PXRD, DSC and SEM in vitro studies. The solubility (13.1 fold) and release of ADL were markedly improved in kneaded ternary ADL/β-CD with 1% poloxamer 188 (KDB). The binding affinity of ADL and β-CD was confirmed by 1H NMR and 2D ROSEY studies. The ternary complex (KDB) was further subjected for in vivo pharmacokinetic studies in rats and a significant improvement in the bioavailability (2.17 fold) was observed in comparison with pure ADL. Therefore, it can be concluded that the solubilization and bioavailability of ADL can be remarkably increased by ADL/β-CD complexation in the presence of a third component, poloxamer 188.

scholarly journals Dissolution Enhancement of Flurbiprofen by Solid Dispersion Adsorbate Technique

2021 ◽  
Vol 69 (2) ◽  
Author(s):  
Sohansinh S. Vaghela ◽  
Samkit M. Shah ◽  
Sanjesh G. Rathi ◽  
Shrenik K. Shah
Keyword(s):  
Solid Dispersion ◽  
Aqueous Solubility ◽  
Dissolution Enhancement ◽  
Phase Solubility ◽  
Fusion Method ◽  
Poloxamer 188 ◽  
X Ray ◽  
Solubility Study ◽  
Phase Solubility Study

Flurbiprofen solid dispersion Adsorbate (SDA) has been prepared using PEG 4000 and Poloxamer 188 as carrier and Neusilin as adsorbent material. The SDA of Flurbiprofen was prepared by using Fusion method in various drugs to carrier ratios. The phase solubility study concludes that both polymers have ability to improve the aqueous solubility of flurbiprofen. Pure API Flurbiprofen and final formulation samples of SDA are characterized by FTIR, DSC and X-ray diffraction spectroscopy. X-ray powder diffraction and DSC study indicated that the drug was present in amorphous form. FTIR study revealed that the characteristic peaks in spectra of pure Flurbiprofen are also present in spectra of SDA’s. Drug found compatible with the excipients. The highest improvement in solubility and in-vitro drug release were observed in solid dispersion prepared with Poloxamer 188 (F14) by fusion method. The increased dissolution rate of drug from solid dispersion adsorbates may be due to surface tension lowering effect of polymer to the medium and increased wettability and dispersibility of drug. Hence, F14 Solid dispersion adsorbates with the Poloxamer carrier in 1:2 ratio considered as most satisfactory among all solid dispersion adsorbates.

scholarly journals Use of Novel Polyurethane Microspheres in a Curcumin Delivery System

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Yongmei Hu ◽  
Qingshan Li ◽  
Wei Hong ◽  
Guangzhong Xing ◽  
Qilong Jiang ◽  
...  
Keyword(s):  
Water Solubility ◽  
Pharmacokinetic Studies ◽  
Pharmacological Effects ◽  
Ph Variation ◽  
Wide Range ◽  
Carboxymethyl Cellulose Sodium ◽  
The Stability ◽  
Scanning Electron

Despite having a wide range of beneficial pharmacological effects, curcumin is characterized by poor water solubility and absorption. In this study, novel polyurethane microspheres containing curcumin (Cur-PUMs) were prepared using carboxymethyl cellulose sodium to improve the bioavailability and prolong the retention time of curcumin. The prepared Cur-PUMs were characterized by Fourier transform infrared spectroscopy, scanning electron microscope, and ultraviolet spectrophotometer. The sustained-release effects of Cur-PUMs were demonstrated using stability testsin vitroandin vivopharmacokinetic studies following oral administration. We found that the stability of Cur-PUMs was strongly affected by pH variation. Further, compared with free curcumin, Cur-PUMs showed significantly improved maximum concentration and half-life.

scholarly journals Preparation of Soluble Complex of Curcumin for the Potential Antagonistic Effects on Human Colorectal Adenocarcinoma Cells

2021 ◽  
Vol 14 (9) ◽  
pp. 939
Author(s):  
Jamal Moideen Muthu Mohamed ◽  
Ali Alqahtani ◽  
Barkat A. Khan ◽  
Adel Al Fatease ◽  
Taha Alqahtani ◽  
...  
Keyword(s):  
Aqueous Solubility ◽  
In Vitro Cytotoxicity ◽  
Phase Solubility ◽  
Soluble Complex ◽  
Zebrafish Model ◽  
Adenocarcinoma Cells ◽  
Hot Melt ◽  
Central Composite

This study was designed to investigate the effects of curcumin (CMN) soluble complex (SC) prepared by melt casting (HM) and hot-melt extrusion (HME) technology. Phase solubility (PS) study, in silico molecular modeling, aqueous solubility, drug release, and physicochemical investigation including a novel dyeing test was performed to obtain an optimized complex by a central composite design (CCD). The results show that the HME-SC produces better improvements towards solubility (0.852 ± 0.02), dissolution (91.87 ± 0.21 % at 30 min), with an ideal stability constant (309 and 377 M−1 at 25 and 37 °C, respectively) and exhibits AL type of isotherm indicating 1:1 stoichiometry. Intermolecular hydrogen bonding involves the formation of SC, which does not undergo any chemical modification, followed by the complete conversion of the amorphous form which was identified by XRD. The in vitro cytotoxicity showed that IC50 was achieved in the SW480 (72 µM.mL−1) and Caco-2 (40 µM.mL−1) cells while that of pure CMN ranged from 146 to 116 µM/mL−1. Apoptosis studies showed that cell death is primarily due to apoptosis, with a low rate of necrosis. In vivo toxicity, confirmed by the zebrafish model, exhibited the safety of the HME-SC. In conclusion, the HME-SC potentially enhances the solubility and cytotoxicity to the treatment of colorectal cancer (CRC).

scholarly journals Overview on Biopharmaceutics Classification System (BCS) based biowaiver requirements in African countries

2021 ◽  
Vol 9 (2) ◽  
pp. 26-29
Author(s):  
Nidhi Sagar ◽  
Iva Dhulia ◽  
Himani Patel ◽  
Umesh Dobariya ◽  
Sandip Sarvaiya
Keyword(s):  
Classification System ◽  
Aqueous Solubility ◽  
Pharmaceutical Product ◽  
Biopharmaceutics Classification System ◽  
In Vivo Studies ◽  
Pharmacokinetic Studies ◽  
African Countries ◽  
Biopharmaceutics Classification

Biopharmaceutics Classification System (BCS)-based biowaiver are meant to reduce the need for establishing in vivo bioequivalence in situations where in vitro data may be considered to provide a reasonable estimate of the relative in vivo performance of two products. The BCS is a scientific approach designed to predict medicinal absorption based on the aqueous solubility and intestinal absorptive characteristics of the Pharmaceutical product. To ensure interchangeability, the multisource product must be therapeutically equivalent to the comparator product. Types of in vivo equivalence studies include comparative pharmacokinetic studies, comparative pharmacodynamic studies and comparative clinical studies. This article briefly explains the BCS based biowaiver requirements in six major African countries i.e. Zimbabwe, South Africa, Uganda, Kenya, Botswana and Tanzania which facilitates regulatory medicine approval process when the dossier (application) is approved based on evidence of equivalence other than In vivo studies.

scholarly journals In Vivo Biocompatible Self-Assembled Nanogel Based on Hyaluronic Acid for Aqueous Solubility and Stability Enhancement of Asiatic Acid

Polymers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 4071
Author(s):  
Yu Yu Win ◽  
Penpimon Charoenkanburkang ◽  
Vudhiporn Limprasutr ◽  
Ratchanee Rodsiri ◽  
Yue Pan ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Water Solubility ◽  
Aqueous Solubility ◽  
Asiatic Acid ◽  
Cell Culture Study ◽  
Nmr Characterization ◽  
The Stability ◽  
Stability Enhancement

Asiatic acid (AA), a natural triterpene found in Centalla asiatica, possesses polypharmacological properties that can contribute to the treatment and prophylaxis of various diseases. However, its hydrophobic nature and rapid metabolic rate lead to poor bioavailability. The aim of this research was to develop a thermoresponsive nanogel from hyaluronic acid (HA) for solubility and stability enhancement of AA. Poly(N-isopropylacrylamide) (pNIPAM) was conjugated onto HA using a carbodiimide reaction followed by 1H NMR characterization. pNIPAM-grafted HA (HA-pNIPAM) nanogels were prepared with three concentrations of polymer, 0.1, 0.15 and 0.25% w/v, in water by the sonication method. AA was loaded into the nanogel by the incubation method. Size, morphology, AA loading capacity and encapsulation efficiency (EE) were analyzed. In vitro cytocompatibility was evaluated in fibroblast L-929 cells using the PrestoBlue assay. Single-dose toxicity was studied using rats. HA-pNIPAM nanogels at a 4.88% grafting degree showed reversible thermo-responsive behavior. All nanogel formulations could significantly increase AA water solubility and the stability was higher in nanogels prepared with high polymer concentrations over 180 days. The cell culture study showed that 12.5 µM AA in nanogel formulations was considered non-toxic to the L-929 cells; however, a dose-dependent cytotoxic effect was observed at higher AA-loaded concentrations. In vivo study proved the non-toxic effect of AA loaded in HA-pNIPAM nanogels compared with the control. Taken together, HA-pNIPAM nanogel is a promising biocompatible delivery system both in vitro and in vivo for hydrophobic AA molecules.

scholarly journals Cyclodextrin Inclusion Complexes of Auranofin and Its Iodido Analog: A Chemical and Biological Study

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 727
Author(s):  
Damiano Cirri ◽  
Ida Landini ◽  
Lara Massai ◽  
Enrico Mini ◽  
Francesca Maestrelli ◽  
...  
Keyword(s):  
Binary Systems ◽  
Current Knowledge ◽  
Aqueous Solubility ◽  
Biological Study ◽  
Phase Solubility ◽  
Cyclodextrin Complex ◽  
Nmr Studies ◽  
Anticancer Properties

Auranofin (AF) and its iodido analog, i.e., Au(PEt3) I (AFI), were reported to exhibit very promising anticancer properties both in vitro and in vivo. However, both these gold compounds have a scarce aqueous solubility that hampers their pharmaceutical use. Here, we explore whether encapsulation of these metallodrugs inside hydroxypropyl-beta–cyclodextrin (HPβ–CD) may lead to an improved biopharmaceutical profile for the resulting adducts. Phase solubility studies, performed at 25 °C in an aqueous buffer, revealed, in both cases, the formation of a 1:1 drug to cyclodextrin complex; a far greater apparent stability constant (K1:1) was measured for AFI compared to AF (331 M−1 versus ca. 30 M−1). NMR studies conducted on the AFI/HPβ–CD system confirmed the formation of a stable 1:1 adduct. Then, binary systems of AF and AFI with HPβ–CD were prepared by colyophilization and characterized by DSC and PXRD. The results revealed the occurrence of drug complexation and/or amorphization for the AFI/HPβ–CD binary system. Afterwards, the antiproliferative properties of the two cyclodextrin adducts and of the corresponding free drugs were comparatively evaluated in vitro in three representative ovarian cancer cell lines, i.e., A2780, SKOV3, and IGROV-1. The results, in all cases, point out that CD complexation of the two gold drugs does not substantially affect their biological activity. The implications of these findings are discussed in the frame of the current knowledge of AF and its analogs.

Formation and Structure of Casein Micelles in Lactating Mammary Tissue

1970 ◽  
Vol 28 ◽  
pp. 150-151
Author(s):  
Robert J. Carroll ◽  
Marvin P. Thompson ◽  
Harold M. Farrell
Keyword(s):  
Size Distribution ◽  
G Protein ◽  
Milk Proteins ◽  
Mammary Tissue ◽  
Colloidal System ◽  
Casein Micelles ◽  
The Stability

Milk is an unusually stable colloidal system; the stability of this system is due primarily to the formation of micelles by the major milk proteins, the caseins. Numerous models for the structure of casein micelles have been proposed; these models have been formulated on the basis of in vitro studies. Synthetic casein micelles (i.e., those formed by mixing the purified αsl- and k-caseins with Ca2+ in appropriate ratios) are dissimilar to those from freshly-drawn milks in (i) size distribution, (ii) ratio of Ca/P, and (iii) solvation (g. water/g. protein). Evidently, in vivo organization of the caseins into the micellar form occurs in-a manner which is not identical to the in vitro mode of formation.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

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.

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