scholarly journals Co-Amorphous Formulations of Furosemide with Arginine and P-Glycoprotein Inhibitor Drugs

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 171
Author(s):  
Marika Ruponen ◽  
Konsta Kettunen ◽  
Monica Santiago Pires ◽  
Riikka Laitinen
Keyword(s):  
Storage Conditions ◽  
Scanning Calorimetry ◽  
Glycoprotein P ◽  
Molar Ratios ◽  
P Glycoprotein ◽  
Permeation Studies ◽  
Poorly Soluble ◽  
Biopharmaceutics Classification ◽  
Permeability Assay ◽  
Simultaneous Dissolution

In this study, the amino acid arginine (ARG) and P-glycoprotein (P-gp) inhibitors verapamil hydrochloride (VER), piperine (PIP) and quercetin (QRT) were used as co-formers for co-amorphous mixtures of a Biopharmaceutics classification system (BCS) class IV drug, furosemide (FUR). FUR mixtures with VER, PIP and QRT were prepared by solvent evaporation, and mixtures with ARG were prepared by spray drying in 1:1 and 1:2 molar ratios. The solid-state properties of the mixtures were characterized with X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) in stability studies under different storage conditions. Simultaneous dissolution/permeation studies were conducted in side-by-side diffusion cells with a PAMPA (parallel artificial membrane permeability assay) membrane as a permeation barrier. It was observed with XRPD that ARG, VER and PIP formed co-amorphous mixtures with FUR at both molar ratios. DSC and FTIR revealed single glass transition values for the mixtures (except for FUR:VER 1:2), with the formation of intermolecular interactions between the components, especially salt formation between FUR and ARG. The co-amorphous mixtures were found to be stable for at least two months under an elevated temperature/humidity, except FUR:ARG 1:2, which was sensitive to humidity. The dissolution/permeation studies showed that only the co-amorphous FUR:ARG mixtures were able to enhance both the dissolution and permeation of FUR. Thus, it is concluded that formulating co-amorphous salts with ARG may be a promising option for poorly soluble/permeable FUR.

scholarly journals Efficient Enhancement in Itraconazole Solubility through its Cyclodextrin-Water Soluble Polymer Ternary Inclusion Complexes

2020 ◽  
Vol 10 (3) ◽  
pp. 11-14
Author(s):  
Dounia SID ◽  
Milad BAITICHE ◽  
Zineb ELBAHRI ◽  
Ferhat DJERBOUA ◽  
Sabrine MESSALTI ◽  
...  
Keyword(s):  
Inclusion Complexes ◽  
Fourier Transforms ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
Soluble Polymer ◽  
Basic Drug ◽  
Water Soluble Polymer ◽  
Molar Ratios ◽  
Poorly Soluble ◽  
Pure Drug

The aim of this work is the enhancement of the hydrosolubility behaviour of a poorly soluble, weakly basic drug, using itraconazole (ITZ) as a case example. Binary inclusion complexes of ITZ with β-cyclodextrin (β-CD) are prepared in 1:2 molar ratios of ITZ to β-CD by co-evaporation method. Both solubility and dissolution behaviour are compared with that of the pure drug. Ternary complexes can be obtained by adding the polyvinylpirrolidone (PVP) which is a highly water soluble polymer, in the ITZ/ β-CD complex formation. Actually, Solid state analysis is performed for all formulations and for pure ITZ applying the Fourier transforms infrared (FT-IR) spectroscopy, powder X-ray diffraction (pX-RD) and differential scanning calorimetry (DSC). Solubility tests indicate that with all formulation, the solubility of ITZ formed with β-CD or β-CD and PVP proved to be increased. The obtained results show that the pure drug has a poor dissolution property, and the ternary inclusion complexes resulted in fast and extensive release of ITZ. Keywords: Itraconazole, β-cyclodextrin, polyvinylpyrrolidone.

scholarly journals Dissolution Enhancement of Atorvastatin Calcium by Cocrystallization

2019 ◽  
Vol 9 (4) ◽  
pp. 559-570 ◽  
Author(s):  
Reham Al-Kazemi ◽  
Yacoub Al-Basarah ◽  
Aly Nada
Keyword(s):  
Dissolution Rate ◽  
Dissolution Enhancement ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Atorvastatin Calcium ◽  
Molar Ratios ◽  
Poorly Soluble ◽  
Poorly Soluble Drug ◽  
Physical Mixtures ◽  
Biopharmaceutical Classification System

Purpose: To enhance the dissolution rate of the poorly soluble drug atorvastatin calcium (ATC) bycocrystallization with selected coformers. Enhancement of the dissolution rate and solubility of thedrug, which is classified as Class II of the Biopharmaceutical Classification System (BCS), is expectedto enhance the bioavailability.Methods: Two methods were used for preparing the cocrystals, solvent drop grinding (SDG) andsolvent evaporation (SE) method using 1:1, 1:3, and 1:10 drug-coformer molar ratios. Glucosaminehydrochloride (GluN) and nicotinamide (NIC) were investigated as coformers. The cocrystals,their physical mixtures, and the raw ATC were characterized by fourier transform infrared (FTIRspectroscopy), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), massspectroscopy (MS), scanning electron microscopy (SEM), solubility, and dissolution rate studies.Results: SDG and SE were effective in improving the dissolution rate of ATC with both coformers.Drug: coformer ratio 1:3 was optimum. The solubility values for ATC, GluN-, and NIC-cocrystals were26, to 35 and 50 μg/mL, respectively. The dissolution rate of ATC from cocrystals was > 90% after 5minutes, compared to 41% untreated ATC.Conclusion: Cocrystallization significantly improved the solubility and dissolution, in comparison tothe untreated ATC.<br />

Studies on the Preparation, Characterization and Solubility of -Cyclodextrin-Roxythromycin Inclusion Complexes

2009 ◽  
Vol 2 (2) ◽  
pp. 523-530
Author(s):  
D. Nagasamy Venkatesh ◽  
S. Karthick ◽  
M. Umesh ◽  
G. Vivek ◽  
R.M. Valliappan ◽  
...  
Keyword(s):  
Dissolution Rate ◽  
Inclusion Complexes ◽  
Phase Solubility ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
X Ray ◽  
Ir Studies ◽  
Poorly Soluble ◽  
Poorly Soluble Drug

Roxythromycin/ β-cyclodextrin (Roxy/ β-CD) dispersions were prepared with a view to study the influence of β-CD on the solubility and dissolution rate of this poorly soluble drug. Phase-solubility profile indicated that the solubility of roxythromycin was significantly increased in the presence of β-cyclodextrin and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes. Physical characterization of the prepared systems was carried out by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD) and IR studies. Solid state characterization of the drug β-CD binary system using XRD, FTIR and DSC revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement of dissolution rate.

Correlation between P-glycoprotein (P-gp) expression in parathyroid and Tc-99m MIBI parathyroid image findings

2001 ◽  
Vol 28 (8) ◽  
pp. 929-933 ◽  
Author(s):  
Shung-Shung Sun ◽  
Yu-Chien Shiau ◽  
Cheng-Chieh Lin ◽  
Albert Kao ◽  
Cheng-Chun Lee
Keyword(s):  
Glycoprotein P ◽  
P Glycoprotein

scholarly journals Stabilisation of Lutein and Lutein Esters with Polyoxyethylene Sorbitan Monooleate, Medium-Chain Triglyceride Oil and Lecithin

Foods ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 500
Author(s):  
Zala Gombač ◽  
Ilja Gasan Osojnik Črnivec ◽  
Mihaela Skrt ◽  
Katja Istenič ◽  
Andreja Knez Knafelj ◽  
...  
Keyword(s):  
Aqueous Solutions ◽  
Medium Chain Triglyceride ◽  
Storage Conditions ◽  
Sorbitan Monooleate ◽  
Medium Chain ◽  
Poorly Soluble

Lutein is a challenging compound to incorporate into food, as it is poorly soluble and unstable in aqueous solutions. In this study, the aim was to prepare stable encapsulates of lutein and lutein esters using feasible and straightforward techniques. Fine suspensions based on polyoxyethylene sorbitan monooleate and medium-chain triglyceride oil micelle-like units with 3.45% lutein esters or 1.9% lutein equivalents provided high encapsulation efficiencies of 79% and 83%, respectively. Lutein encapsulated in fine suspensions showed superior stability, as 86% was retained within the formulation over 250 days at 25 °C in the dark. Under the same storage conditions, only 38% of lutein remained in corresponding formulations. Higher encapsulation efficiencies were achieved with lecithin emulsions, at up to 99.3% for formulations with lutein, and up to 91.4% with lutein esters. In lecithin emulsions that were stored for 250 days, 17% and 80% of lutein and lutein esters, respectively, were retained within the formulations.

Molecular docking studies of tea (Thea sinensis Linn.) polyphenols inhibition pattern with Rat P-glycoprotein

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Babar Ali ◽  
Qazi Mohammad Sajid Jamal ◽  
Showkat R. Mir ◽  
Saiba Shams ◽  
Mohammad Amjad Kamal
Keyword(s):  
Amino Acids ◽  
Molecular Docking ◽  
Binding Energy ◽  
Oral Administration ◽  
Docking Studies ◽  
Vital Role ◽  
Glycoprotein P ◽  
High Affinity ◽  
P Glycoprotein ◽  
Inhibition Pattern

AbstractSince 3000 B.C., evergreen plant Thea sinensis (Theaceae) is used both as a social and medicinal beverage. Leaves of T. sinensis contain amino acids, vitamins, caffeine, polysaccharides and polyphenols. Most of the natural medicinal actions of tea are due to the availability and abundance of polyphenols mainly catechins. It has also been stated that some catechins were absorbed more rapidly than other compounds after the oral administration of tea and could increase the bio-enhancing activities of anticancer drugs by inhibiting P-glycoprotein (P-gp). The results of the molecular docking showed that polyphenols bind easily to the active P-gp site. All compounds exhibited fluctuating binding affinity ranged from −11.67 to −8.36 kcal/mol. Observed binding energy required for theaflavin to bind to P-gp was lowest (−11.67 kcal/mol). The obtained data that supports all the selected polyphenols inhibited P-gp and therefore may enhance the bioavailability of drugs. This study may play a vital role in finding hotspots in P-gp and eventually may be proved useful in designing compounds with high affinity and specificity to the protein.

scholarly journals Stability and Influence of Storage Conditions on Nanofibrous Film Containing Tooth Whitening Agent

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 449
Author(s):  
Siriporn Okonogi ◽  
Adchareeya Kaewpinta ◽  
Pisaisit Chaijareenont
Keyword(s):  
Water Absorption ◽  
Storage Condition ◽  
Storage Conditions ◽  
Scanning Calorimetry ◽  
Adhesive Properties ◽  
Tooth Whitening ◽  
Electrospinning Technique ◽  
Long Term Storage ◽  
Whitening Agent ◽  
Nanofibrous Structure

Carbamide peroxide (CP), a tooth whitening agent, is chemically unstable. The present study explores stability enhancement of CP by loading in a nanofibrous film (CP-F) composed of polyvinyl alcohol/polyvinylpyrrolidone/silica mixture, using an electrospinning technique. Kept at a temperature range of 60–80 °C for 6 h, CP in CP-F showed significantly higher stability than that in a polymer solution and in water, respectively. Degradation of CP in CP-F could be described by the first order kinetics with the predicted half-life by the Arrhenius equation of approximately 6.52 years. Physicochemical properties of CP-F after long-term storage for 12 months at different temperatures and relative humidity (RH) were investigated using scanning electron microscopy, X-ray diffractometry, differential scanning calorimetry, and Fourier transform infrared spectroscopy. It was found that high temperature and high humidity (45 °C/75% RH) could enhance water absorption and destruction of the nanofibrous structure of CP-F. Interestingly, kept at 25 °C/30% RH, the nanofibrous structure of CP-F was not damaged, and exhibited no water absorption. Moreover, the remaining CP, the mechanical properties, and the adhesive properties of CP-F were not significantly changed in this storage condition. It is concluded that the developed CP-F and a suitable storage condition can significantly improve CP stability.

scholarly journals Pulchinenosides from Pulsatilla Chinensis Increase P-Glycoprotein Activity and Induce P-Glycoprotein Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yali Liu ◽  
Ling Zhang ◽  
Shaofeng Wei ◽  
Jinyang Cai ◽  
Zhenzhong Zang ◽  
...  
Keyword(s):  
Membrane Vesicles ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Intestinal Epithelial ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Human Intestinal Epithelial Cells ◽  
Pulsatilla Chinensis ◽  
Dependent Transport ◽  
Cytotoxic Studies

Five pulchinenosides (pulchinenoside B3, pulchinenoside BD, pulchinenoside B7, pulchinenoside B10, and pulchinenoside B11) isolated from Pulsatilla chinensis (Bge) Regel saponins extract exhibited strong antitumor activities but poor gastrointestinal absorption properties. The enteric induction of P-glycoprotein (P-gp) is understood to restrict the oral bioavailability of some pharmaceutical compounds and lead to adverse drug reactions. Therefore, the present investigation was intended to delineate the impacts of pulchinenosides on cellular P-gp function and expression using Sf9 membrane vesicles and LS180 cells as a surrogate of human intestinal epithelial cells. Preliminary cytotoxic studies showed that 10 μM was an acceptable concentration for cytotoxicity and antiproliferation studies for all pulchinenosides using the alamarBlue assay. The cell cycle of LS180 cells detected by flow cytometry was not significantly influenced after 48 hours of coincubation with 10 μM of pulchinenosides. In the presence of pulchinenosides, the ATP-dependent transport of N-methyl-quinidine mediated by P-glycoprotein was stimulated significantly. The upregulation of P-glycoprotein and mRNA levels was found by Western blot and real-time PCR analysis in LS180 cells. Parallel changes indicate that all pulchinenosides are exposed to pulchinenosides-mediated transcriptional regulation. In conclusion, pulchinenosides could induce P-glycoprotein expression and directly increase its functional activity.

Sign in / Sign up

Export Citation Format

Share Document