Publications by authors named "Amal K Hussein"

13 Publications

  • Page 1 of 1

A Novel Nanoemulsion Intermediate Gel as a Promising Approach for Delivery of Itraconazole: Design, In Vitro and Ex Vivo Appraisal.

AAPS PharmSciTech 2020 Oct 6;21(7):272. Epub 2020 Oct 6.

Pharmaceutics Department, Faculty of Pharmacy, Minia University, P.O. Box: 61111, Minia, Egypt.

The aim the study was to design, formulate, and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) of itraconazole for improving the topical antifungal properties of the drug by adopting the nanoemulsion intermediate gel of the optimized system. Solubility study was conducted to select the most appropriate oils and surfactants for formulation. Different possible systems were created. Ternary phase diagrams were constructed to select the most promising system for further study. The nanoemulsion intermediate gel of the selected system was evaluated for stability, dilution effect, viscosity, pH, antifungal activity, droplet size, PDI, and zeta potential. In vitro release of the drug from the selected intermediate gel was investigated, and the kinetic model of drug release was determined. Ex vivo permeation of itraconazole was studied, and the amount of drug accumulated in the skin was calculated. Solubility and phase diagrams revealed that the system consisting of 60% cotton seed oil and 40% span 80 provided the nanoemulsion intermediate gel with the highest drug concentration. The selected system had a droplet size of about 236 nm and zeta potential of - 59.8. The viscosity of the corresponding intermediate gel was 1583.47 cp. The system exhibited high stability at 4°C and 25°C for 12 months and improved antifungal activity. In vitro release study showed complete release of itraconazole within 4 h, while the ex vivo permeation study revealed accumulation of the majority of the drug within the skin layers (72.5%).
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http://dx.doi.org/10.1208/s12249-020-01830-wDOI Listing
October 2020

Polymeric micelles for the ocular delivery of triamcinolone acetonide: preparation and evaluation in a rabbit ocular inflammatory model.

Drug Deliv 2020 Dec;27(1):1115-1124

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt.

The aim of this study was to prepare triamcinolone acetonide (TA)-loaded poly(ethylene glycol)--poly(ε-caprolactone) (PEG--PCL) and poly(ethylene glycol)--poly(lactic acid) (PEG--PLA) micelles as a potential treatment of ocular inflammation. The micelles were evaluated for particle size, drug loading capacity and drug release kinetics. Selected micellar formulations were dispersed into chitosan hydrogel and their anti-inflammatory properties were tested in rabbits using a carrageenan-induced ocular inflammatory model. Particle size ranged from 59.44 ± 0.15 to 64.26 ± 0.55 nm for PEG--PCL and from 136.10 ± 1.57 to 176.80 ± 2.25 nm for PEG--PLA micelles, respectively. The drug loading capacity was in the range of 6-12% and 15-25% for PEG--PCL and PEG--PLA micelles, respectively and was dependent on the drug/polymer weight ratio. TA aqueous solubility was increased by 5- and 10-fold after loading into PEG--PCL and PEG--PLA micelles at a polymer concentration as low as 0.5 mg/mL, respectively. PEG--PLA micelles suspended in chitosan hydrogel were able to sustain the drug release where only 42.8 ± 1.6% drug was released in one week. TA/PEG--PLA micelles suspended in chitosan hydrogel had better anti-inflammatory effects compared with the plain drug hydrogel or the drug micellar solution. Complete disappearance of the corneal inflammatory changes was observed for the micellar hydrogel. These results confirm the potential of PEG--PLA micelles suspended in chitosan hydrogel to enhance the anti-inflammatory properties of triamcinolone acetonide.
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http://dx.doi.org/10.1080/10717544.2020.1797241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470058PMC
December 2020

Oxiconazole nitrate solid lipid nanoparticles: formulation, in-vitro characterization and clinical assessment of an analogous loaded carbopol gel.

Drug Dev Ind Pharm 2020 May 15;46(5):706-716. Epub 2020 Apr 15.

Department of Pharmaceutics, Faculty of Pharmacy, Minia University, El Minia, Egypt.

The aim of the present work was to develop a promising drug delivery system of oxiconazole nitrate-loaded solid lipid nanoparticles (SLNs) topical gel to enhance the drug effectiveness for the treatment of Tinea infection. SLNs were prepared by emulsification-solvent evaporation method. Particle size and entrapment efficiency of the prepared SLNs were investigated. An appropriate formulation was selected and examined for morphology and physicochemical characterization adopting Scanning electron microscope and Differential scanning colorimetry. In-vitro drug release was also investigated. The selected SLNs were loaded into 1% Carbopol 934 gel that was investigated for homogeneity, pH, grittiness, spreadability, viscosity and drug release. Clinical study for the developed gel system compared to the corresponding marketed product was conducted on 28 patients. The results revealed that the prepared oxiconazole nitrate SLNs had drug entrapment efficiency ranging from 41.34% to 75.07% and zeta potential lying between -13 and -50. Physicochemical characterization revealed a decrease in the drug crystallinity in the prepared SLNs. The gel formulation showed appropriate physical characteristics and sustained in-vitro drug release. Clinical study for the prepared oxiconazole nitrate SLNs gel showed significantly less side effects, better patient satisfaction and superior clinical improvement compared with the corresponding marketed product.
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http://dx.doi.org/10.1080/03639045.2020.1752707DOI Listing
May 2020

Best tigecycline dosing for treatment of infections caused by multidrug-resistant pathogens in critically ill patients with different body weights.

Drug Des Devel Ther 2018 7;12:4171-4179. Epub 2018 Dec 7.

Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt.

Background: The intensive care unit (ICU) is a center of multidrug-resistant (MDR) pathogens. This is due to overuse of antibiotics in the treatment of critically ill patients. Tigecycline is a broad-spectrum antibiotic that belongs to the glycylcycline group. Tigecycline has been indicated in treatment of complicated intra-abdominal infections (cIAIs) and complicated skin and soft-tissue infections (cSSTIs).

Objective: This study was done to discover the best dose regimen of tigecycline in treatment of cSSTIs and cIAIs, especially in patients who are critically ill and obese, for clinical outcomes and safety.

Setting: The study was conducted in an adult ICU that consists of 25 beds in a general hospital and was conducted within 2 years. A total of 954 patients were screened in this study.

Methods: This was a retrospective cohort study that compared the clinical outcomes of patients: mortality, ICU stay, and safety of using two different dose regimens of tigecycline between patients with different body weight who were treated for infections caused by MDR pathogens in the ICU. The study was conducted within 2 years. All results were collected from patients' files and were analyzed with SPSS version 20.

Main Outcome: The study was implemented to figure out the best dose regimen of tigecycline to achieve a reduction in mortality, ICU stay, treatment duration, and secondary septic-shock incidence with minimum side effects in treatment of cSSTIs and cIAIs in patients with different body weight.

Results: There was a significant improvement in mortality, ICU stay, recurrent infection by the same organism, duration of tigecycline treatment, number of patients who had first negative culture after starting treatment, secondary bacteremia, and secondary septic shock with patients who used high-dose regimens of tigecycline in different subgroups of body weight, with no significant difference in side effects.

Conclusion: The use of high-dose tigecycline resulted in a significant enhancement in all clinical outcomes, especially mortality and ICU stay when used in treatment of overweight and obese patients with cSSTIs and cIAIs.
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http://dx.doi.org/10.2147/DDDT.S181834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290867PMC
May 2019

Real Life Egyptian Experience of Daclatasvir Plus Sofosbuvir with Ribavirin in Naïve Difficult to Treat HCV Patients.

Infect Disord Drug Targets 2020 ;20(1):43-48

Department of Biochemistry, Egyptian Ministry of Interior, Cairo, Egypt.

Background: Chronic infection with Hepatitis C virus (HCV) is considered as a major cause for developing liver cirrhosis and hepatocellular carcinoma. A new era in HCV treatment is ongoing using Direct Acting Antiviral activity (DAA). The first approved DAA drug was Sofosbuvir which has a high tolerability and preferable pharmacokinetic profile. Another recently developed drug is Daclatasvir a first-in-class HCV NS5A replication complex inhibitor. Both drugs are administered orally once daily and have potent antiviral activity with wide genotypic coverage.

Methods: In the outpatient clinic, one hundred and fifty naïve difficult to treat chronic HCV patients were recruited from Tropical Medicine Department at Fayoum public hospital. A combination of Daclatasvir (60 mg) and Sofosbuvir (400 mg) (DCV/SOF) has been administered for those patients once daily with Ribavirin (1200 mg or 1000 mg based on patients' weight on two divided doses) over a period of 12 weeks. All patients have been followed up for clinical, laboratory assessment and HCV PCR to detect the efficacy and safety of the therapy.

Results: Sustained Virologic Response rate (SVR12) was achieved in the vast majority of patients (90.67%). Cirrhotic patients showed lower SVR compared to non-cirrhotic patients (88.89% vs 90.91%, respectively). Around half of the patients (49.33%) developed adverse events (AEs) during treatment. The most common AEs were headache, fatigue and abdominal pain.

Conclusion: The available evidence seems to suggest that combination therapy of (DCV/SOF with RBV) in the treatment of chronic HCV genotype IV naïve difficult to treat patients either cirrhotic or non-cirrhotic is safe and effective. Monitoring for clinical and laboratory hepatic parameters was the basis for these findings.
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http://dx.doi.org/10.2174/1871526518666180716141806DOI Listing
October 2020

Extended infusion versus intermittent infusion of imipenem in the treatment of ventilator-associated pneumonia.

Drug Des Devel Ther 2017 6;11:2677-2682. Epub 2017 Sep 6.

Department of Pharmaceutics.

Background: Mechanical ventilation support can be the main source of ventilator-associated pneumonia (VAP). VAP is a serious infection that may be associated with dangerous gram-negative bacteria mainly, and it leads to an increase in the mortality in the intensive care unit (ICU). Imipenem is one of the strongest antibiotics now available for treating VAP which is associated with gram-negative and gram-positive bacteria, and it belongs to beta-lactam antibiotic group (carbapenem).

Objective: This study tried to investigate the efficacy of imipenem against VAP when it was infused within 180 min versus the efficacy when it was infused within 30-60 min.

Setting: This study was conducted in main ICU in general hospital which consists of surgical and medical beds within 2 years. One hundred and eighty-seven patients were enrolled on it.

Method: This study is a retrospective cohort which was conducted within 2 years. The efficacy of imipenem which was administered by intermittent infusion (30-60 min) within first year was compared with the efficacy of imipenem which was administered by extended infusion (180 min) within second year in the field of VAP curing and cost reduction. All data were collected retrospectively from patient medical files and were statistically analyzed by SPSS version 20.

Main Outcome: The study was designed to measure clinical and cost reduction outcomes, mortality and hospital stay.

Results: The results indicated that there is a significant decrease in mortality, number of recurrent infection, and ICU stay length, and the number of mechanical ventilator days was associated with extended imipenem infusion during the second year of the study.

Conclusion: The use of imipenem with extended infusion over 3 hours enhances its clinical outcomes in the treatment of VAP.
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http://dx.doi.org/10.2147/DDDT.S143021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593413PMC
June 2018

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies.

Eur J Pharm Biopharm 2017 May 24;114:119-134. Epub 2017 Jan 24.

School of Pharmacy and Chemistry, Faculty of Science, Engineering & Computing, Kingston University, London, UK; School of Pharmacy, The University of Auckland, Auckland, New Zealand.

This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using DSC and FT-IR. The gelation temperature (T), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. DSC and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. P188 modified the T of P407 bringing it close to eye temperature (35°C) compared with the formulation containing P407 alone. Moreover, gels that comprised P407 and P188 exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations PP11 and PP12, the work of adhesion decreased significantly (P<0.001) from 377.9±7.79mNmm to 272.3±6.11mNmm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control KT release as only 48% of the KT released within 12h. In addition, the HET-CAM and BCOP tests confirmed the non-irritancy of KT loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. MTT assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with KT showed reasonable and acceptable percent cell viability compared with control samples.
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http://dx.doi.org/10.1016/j.ejpb.2017.01.008DOI Listing
May 2017

Flurbiprofen-loaded niosomes-in-gel system improves the ocular bioavailability of flurbiprofen in the aqueous humor.

Drug Dev Ind Pharm 2017 Jun 31;43(6):902-910. Epub 2017 Jan 31.

a Department of Pharmaceutics, Faculty of Pharmacy , Minia University , Minia , Egypt.

The present work aimed to prolong the contact time of flurbiprofen (FBP) in the ocular tissue to improve the drug anti-inflammatory activity. Different niosome systems were fabricated adopting thin-film hydration technique and using the nonionic surfactant Span 60. The morphology of the prepared niosomes was characterized by scanning electron microscopy (SEM). Physical characterization by differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy were conducted for the optimized formula (F5) that was selected on the basis of percent entrapment efficiency, vesicular size and total lipid content. F5 was formulated as 1% w/w Carpobol 934 gel. Pharmacokinetic parameters of FBP were investigated following ocular administration of F5-loaded gel system, F5 niosome dispersion or the corresponding FBP ocular drops to albino rabbits dispersion. Anti-inflamatory effect of F5-loaded carbopol gel was investigated by histopathological examination of the corneal tissue before and after the treatment of inflamed rabbit eye with the system. Results showed that cholesterol content, surfactant type. and total lipid contents had an apparent impact on the vesicle size of the formulated niosomes. Physical characterization revealed reduced drug crystallinity and incidence of interaction with other niosome contents. F5-loaded gel showed higher C, area under the curve (AUC), and thus higher ocular bioavailability than those of the corresponding FBP ocular solution. F5-loaded gel showed a promising rapid anti-inflammatory effect in the inflamed rabbit eye. These findings will eradicate the necessity for frequent ocular drug instillation and thus, improve patient compliance.
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http://dx.doi.org/10.1080/03639045.2016.1272120DOI Listing
June 2017

Formulation and clinical evaluation of silymarin pluronic-lecithin organogels for treatment of atopic dermatitis.

Drug Des Devel Ther 2016 10;10:1101-10. Epub 2016 Mar 10.

Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt.

Silymarin is a naturally occurring flavonoid drug; evidence from recent research has highlighted its use as a potential treatment for atopic dermatitis (AD). Both poor water solubility and drug permeability have hindered the percutaneous absorption of silymarin. Formulation of silymarin into pluronic-lecithin organogel (PLO) basis for topical skin delivery is the main aim of this work. Six different PLO formulations were prepared containing various pluronic to lecithin ratios using two cosolvent systems of ethyl alcohol and dimethyl sulfoxide. Formulation 2 (20% pluronic and 3% lecithin) was found to be the optimal base for topical delivery of silymarin as it showed optimum pH, viscosity, drug content, and satisfactory in vitro silymarin permeation. The silymarin PLO formulation significantly relieved inflammatory symptoms of AD such as redness, swelling, and inflammation. These findings warrant the ability for application of these novel silymarin PLO formulations as a novel treatment for AD.
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http://dx.doi.org/10.2147/DDDT.S103423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4790491PMC
December 2016

Optimisation of microstructured biodegradable finasteride formulation for depot parenteral application.

J Microencapsul 2016 May 17;33(3):229-38. Epub 2016 Feb 17.

b Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy , Taibah University , Medina , Saudi Arabia ;

This study aimed to use the biocompatibility features of the biodegradable polymers to prepare depot injectable finasteride (FIN) microspheres for the treatment of benign prostatic hyperplasia. FIN microspheres were prepared utilising an emulsion-solvent evaporation/extraction technique. The Box-Behnken experimental design was adopted to optimise the preparation process. FIN plasma levels in albino rabbits were determined after injection with optimised FIN microspheres formula and compared with oral FIN suspension. Results revealed that the optimum microspheres displayed an amended sustained release pattern with lower initial burst. The cumulative FIN % released after 25 days was in the range 27.83-73.18% for F4 and F1, respectively. The optimised formula, with 50.0% (X1), and 22.316% (X2) and 1.38% (X3) showed 6.503 μm, 93.213%, 14.574%, and 64.838% for Y1, Y2, Y3, and Y4, respectively. In vivo studies displayed a sustained release pattern with minimal initial burst release when injected into rabbits.
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http://dx.doi.org/10.3109/02652048.2016.1144821DOI Listing
May 2016

Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles.

Drug Dev Ind Pharm 2016 25;42(4):514-24. Epub 2015 Sep 25.

b School of Pharmacy and Chemistry, Faculty of Science, Engineering & Computing, Kingston University , London , UK , and.

The aim of this work was to formulate chitosan (CS)-based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimized in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterization studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0 ± 2.4 nm to 257.2 ± 18.6 nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10 mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (p < 0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT-loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS-based NPs for the ocular delivery of KT.
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http://dx.doi.org/10.3109/03639045.2015.1081236DOI Listing
December 2016

Improved corneal bioavailability of ofloxacin: biodegradable microsphere-loaded ion-activated in situ gel delivery system.

Drug Des Devel Ther 2015 10;9:1427-35. Epub 2015 Mar 10.

Department of Pharmaceutical Technology, Faculty of Pharmacy, Minia University, Minia, Egypt ; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

The aim of the study was to improve corneal penetration and bioavailability of ofloxacin (OFX) eye preparations. OFX was incorporated in poly (lactide-co-glycolide) as biodegradable microspheres using oil in oil emulsion solvent evaporation technique. The prepared OFX microspheres were then incorporated in Gelrite(®) in situ gel preparation. In addition, OFX Gelrite-based in situ gel formulations were prepared. OFX formulations were characterized for gelling capacity, viscosity, and rheological properties. Release studies for OFX microspheres, OFX in situ gel, and OFX-loaded microspheres in situ gel formulations were carried out to investigate release characteristics of the drug. The prepared OFX formulations were then investigated in vivo compared with commercially available OFX eyedrops. Results showed that the optimum Gelrite concentration was at 0.4%-0.7% w/v; the prepared formulations were viscous liquid transformed into a pourable gel immediately after the addition of simulated tear fluid with a gelling factor of 27-35. Incorporation of OFX-loaded microspheres in Gelrite solution (0.4% w/v) significantly altered the release profiles of OFX-loaded microspheres in situ gel formula compared with the corresponding OFX gels and OFX microspheres. In vivo results in rabbits showed that OFX-loaded microspheres in situ gel formula improved the relative bioavailability by 11.7-fold compared with the commercially available OFX eyedrops. In addition, the longer duration of action of OFX-loaded microspheres in situ gel formula preparations is thought to avoid frequent instillations, which improves patient tolerability and compliance.
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http://dx.doi.org/10.2147/DDDT.S80697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362657PMC
August 2016

Formulation and evaluation of meloxicam niosomes as vesicular carriers for enhanced skin delivery.

Pharm Dev Technol 2013 Jul-Aug;18(4):779-86. Epub 2011 Sep 14.

Department of Pharmaceutics and Industrial Pharmacy, Beni Suef University, Beni Suef, Egypt.

Context: Skin delivery of Meloxicam (MX) offers several advantages over the oral route which is associated with potential side effects.

Objectives: The aim of this study was to develop transdermal MX in niosomes.

Materials And Methods: Vesicles prepared by thin film hydration method were characterized and the acute anti-inflammatory activity of 0.5% MX niosomal hydrogel was evaluated using carrageenan induced rat paw edema method.

Results: The results revealed that niosomes prepared from span 60 and cholesterol at 6:4 molar ratio using 20 mg of MX were of the highest entrapment efficiency (> 55%) and with particle size (187.3 nm). There was a marked increase in the percentage inhibition of edema in animals treated with MX vesicular gel compared to those treated with free MX and piroxicam gels.

Discussion: There was an inverse proportionality between vesicle size and cholesterol content. With increased cholesterol molar ratio the bilayer stability increased and permeability decreased leading to efficiently trapping the MX. In contrast, higher amounts of cholesterol may compete with the drug for packing space within the bilayer. The inhibitory effect of MX niosomal gel may be attributed to its superior skin permeation.

Conclusions: The results suggest that niosomes may be promising vehicles for transdermal delivery of MX.
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http://dx.doi.org/10.3109/10837450.2011.598166DOI Listing
December 2013