Researcher:
Fael, Hanan

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Researcher

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Hanan

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Fael

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Fael, Hanan

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Now showing 1 - 4 of 4
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    Publication
    Poly(2-ethyl-2-oxazoline) as an alternative to poly(vinylpyrrolidone) in solid dispersions for solubility and dissolution rate enhancement of drugs
    (Elsevier Science Inc, 2018) Rafols, Clara; N/A; Department of Chemistry; Department of Chemistry; Fael, Hanan; Demirel, Adem Levent; Other; Faculty Member; N/A; College of Sciences; N/A; 6568
    Poly(2-ethyl-2-oxazoline) (PEOX), a biocompatible polymer considered as pseudopolypeptide, was introduced as a potential alternative to the commonly used polymer, poly(vinylpyrrolidone) (PVP) for the preparation of solid dispersion with a poorly soluble drug. Glipizide (GPZ), a Biopharmaceutical Classification System class II model drug, was selected for solubility and dissolution rate study. GPZ-polymer solid dispersions and physical mixtures were characterized and investigated by X-ray diffractometry, differential scanning calorimetry, scanning electron microscopy, and FTIR spectroscopy. The impact of polymers on crystal nucleation kinetics was studied, and PEOX exhibited strong inhibitory effect compared with PVP. Solubility and dissolution behavior of the prepared solid dispersions and their physical blends were in vitro examined and evaluated. A significant enhancement in GPZ solubility was obtained with PEOX compared with the pure drug and solid dispersion with PVP. A big improvement in the intrinsic dissolution rate (45 times) and dissolved amount of GPZ (58 times) was achieved with PEOX in fasted state simulated intestinal fluid, against comparable enhancement observed with PEOX and PVP in phosphate buffer at pH 6.8. Lower molecular weight of PEOX-5K (5000 g/mol) was found to be superior to higher molecular weight PEOX-50K (50,000 g/mol) in the improvement of dissolution behavior. The findings of this study with GPZ as a model drug introduce lower molecular weight PEOX as a promising polymeric carrier toward better oral bioavailability of poorly soluble drugs. (c) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
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    Publication
    Tannic acid as a co-former in co-amorphous systems: Enhancing their physical stability, solubility and dissolution behavior
    (Elsevier, 2020) N/A; Department of Chemistry; Department of Chemistry; Department of Chemistry; Fael, Hanan; Demirel, Adem Levent; Researcher; Faculty Member; College of Sciences; College of Sciences; N/A; 6568
    Co-amorphous systems have been increasingly investigated to improve the solubility and dissolution rate of poorly soluble drugs. Considering the ability of tannic acid (TA), a polyphenolic compound, to form hydrogen bonds with compounds that contain carbonyl groups, we hypothesized that tannic acid will also be effective in stabilizing amorphous form of drugs in co-amorphous systems. Co-amorphization by TA of two poorly soluble model drugs, carbamazepine (CBZ) and indomethacin (IND) was investigated. Tannic acid facilitated the amorphization of studied drugs and successful co-amorphous systems were obtained as proved by powder X-Ray diffraction (PXRD). Differential scanning calorimetry (DSC) confirmed the homogeneous structure as indicated by the existence of a single T-g for each co-amorphous product. The expected molecular interactions between phenolic groups in TA and carbonyl groups in the studied drugs (CBZ and IND) were confirmed by analyzing their infrared spectra. Drug-TA co-amorphous formulations showed an enhanced equilibrium solubility over the individual drugs. Powder dissolution WA under sink conditions showed improved dissolution profiles of drug-TA co-amorphous formulations compared to the corresponding crystalline drugs and physical mixtures. Tannic acid also showed a superior stabilizing effect. CBZ-TA co-amorphous system was physically stable at dry conditions (up to 6 months at 40 degrees C), under 60% relative humidity (up to one month at 20 degrees C), and in solution (after 48 h of solubility measurements), as revealed by PXRD examination of the remaining solid after solubility measurement. However, IND-TA co-amorphous formulation remained stable at dry conditions up to 6 months at 4 degrees C and up to one month at 60% relative humidity at 20 degrees C. These findings demonstrate the potential of tannic acid as a promising co-former in co-amorphous systems of poorly soluble drugs.
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    Publication
    Indomethacin co-amorphous drug-drug systems with improved solubility, supersaturation, dissolution rate and physical stability
    (Elsevier, 2021) N/A; Department of Chemistry; Department of Chemistry; Department of Chemistry; Fael, Hanan; Demirel, Adem Levent; Researcher; Faculty Member; College of Sciences; College of Sciences; N/A; 6568
    In this study, new co-amorphous drug systems were designed using a pharmacologically relevant combination to improve the solubility and dissolution of indomethacin. Combinations of indomethacin-paracetamol (IND-PAR) as an anti-inflammatory/pain killer, and indomethacin-nicotinamide (IND-NCT) for prevention of gastric ulcers caused by IND, were developed for co-amorphization. The effect of PAR and NCT on the solubility, supersaturation, and dissolution of the poorly soluble counterpart, IND, was investigated. PAR and NCT were found to enhance the solubility and supersaturation of IND in biorelevant medium (FaSSIF) and in FaSSIF blank. Differential scanning calorimetry (DSC) showed capability of IND-PAR and IND-NCT binary mixtures to form eutectic mixture. Powder X-ray diffraction and DSC indicated the formation of a homogenous co-amorphous system with single T-g value. Hydrogen bonding between IND and each of PAR and NCT were found to stabilize the co-amorphous systems as supported by FTIR studies. The intrinsic dissolution rate under sink conditions was improved over that of plain amorphous IND both in FaSSIF and FaSSIF blank. IND-PAR 2:1 and IND-NCT 1:1 were extremely stable and remained amorphous for 7 months at 25 degrees C, while all co-amorphous formulations were stable at least up to one month at 40 degrees C under dry condition. The present work demonstrates an improved approach to combine IND-PAR and IND-NCT as promising co-amorphous systems for potential therapeutical applications.
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    PublicationOpen Access
    Nisin/polyanion layer-by-layer films exhibiting different mechanisms in antimicrobial efficacy
    (Royal Society of Chemistry (RSC), 2020) Department of Chemistry; Department of Chemistry; Demirel, Adem Levent; Fael, Hanan; Faculty Member; College of Sciences; Graduate School of Sciences and Engineering; 6568; N/A
    Nisin/polyanion Layer-by-Layer (LbL) films are reported to exhibit different mechanisms in antimicrobial efficacy depending on the type of polyanion. LbL films consisting of nisin as the polycationic component were prepared using two different polyanionic constituents: poly acrylic acid (PAA) and dextran sulfate (DX). Due to the weaker interaction strength of carboxylate groups with nisin compared to sulfate/nisin, a larger molecular weight of PAA was needed to achieve LbL assembly. PAA-100K/nisin and DX-15K/nisin multilayer films exhibited significantly different properties. PAA-nisin films grew faster compared to DX-nisin films and showed, for 60 bilayer films, an average bilayer thickness of 21.6 nm compared to that of 6.1 nm in DX-nisin films. The total amount of nisin was found to be 17.1 ± 2.2 ?g cm-2 in (PAA-nisin)60 and 6.8 ± 0.4 ?g cm-2 in (DX-nisin)60 films. The stability of the films was investigated at three different pH values of 6.0, 7.4 and 9.5. (PAA-nisin)60 films exhibited the release of nisin into the solution which resulted in the disintegration of the film over several hours. A burst release was observed in the first hour followed by a slower release and disintegration over 24 hours with a complete release at pH 9.5. The bacterial growth inhibition test against Staphylococcus epidermidis confirmed the antimicrobial activity of nisin released from PAA-nisin films. PAA was found to stabilize nisin and the film-released nisin retained its antimicrobial activity in the neutral and alkaline pH values. Unlike PAA-nisin films, (DX-nisin)60 films were stable at the physiological conditions up to 14 days with no release of nisin. DX-nisin films were found to inhibit the attachment of Staphylococcus epidermidis and prevent biofilm formation. These results clearly demonstrate the effect of different polyanions on nisin LbL films to achieve different mechanisms in antimicrobial efficacy and show the potential of PAA-nisin multilayer films as promising local delivery systems for treatment of burns and wounds, while DX-nisin multilayer films can be employed as stable coatings against bacterial attachment and biofilm formation.