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2022
Elshafeey, A. H., and R. M. El-Dahmy, A novel oral medicated jelly for enhancement of etilefrine hydrochloride bioavailability: In vitro characterization and pharmacokinetic evaluation in healthy human volunteers, , 2022. AbstractWebsite

Etilefrine hydrochloride (ET) is a water-soluble drug that is used to treat hypotension, but it has a bitter taste and low bioavailability due to undergoing the first-pass effect. Thus, this study aimed to develop and evaluate oral medicated jelly (OMJ) containing ET that could offer an easily taken palatable dosage form with higher bioavailability. OMJ is a novel palatable drug delivery system that can easily be taken by pediatric and geriatric patients, as well as those with dysphagia. Moreover, OMJs offer rapid disintegration in saliva and rapid drug absorption through the buccal mucosa, avoiding the first-pass effect and increasing the drug bioavailability. Natural polymers such as pectin, guar gum, xanthan gum, tragacanth gum, and sodium alginate were used as jellifying agents, with the addition of calcium chloride as a crosslinking agent, to prepare OMJs using the heat and congealing method. The prepared OMJs were investigated by testing their viscosity, in vitro release, and texture analysis of firmness, consistency, stickiness, cohesiveness, springiness, gumminess, and chewiness using a texture analyzer. A full factorial design (21 × 51) was utilized to select the optimized OMJ. The optimized OMJ (J2), containing 4 % pectin, had a 7563 ± 55 cps viscosity, 8.32 ± 0.21 N firmness, 5.72 ± 0.18 µJ consistency, 1.30 ± 0.04 mJ stickiness, and 96.02 ± 3.74 % ET dissolved after 10 min. ET release was significantly increased (greater than4-fold) from the optimized OMJ compared with the market tablet. Moreover, the obtained results clarified the stability and the acceptable palatability of the optimized OMJ. The clinical investigation on healthy human volunteers revealed that the optimized OMJ (J2) had significantly higher Cmax (1.7 folds) when compared with the market tablet with a relative bioavailability of 154.55 %. Therefore, OMJs can be considered as promising, palatable, and easily swallowed dosage form that could enhance the bioavailability of drugs undergoing the first-pass effect.

2021
Mosallam, S., N. M. Sheta, A. H. Elshafeey, and A. A. Abdelbary, "Fabrication of Highly Deformable Bilosomes for Enhancing the Topical Delivery of Terconazole: In Vitro Characterization, Microbiological Evaluation, and In Vivo Skin Deposition Study", AAPS PharmSciTech, vol. 22, no. 2, pp. 74, February, 2021. AbstractWebsite

The current study aimed to load terconazole (TCZ), an antifungal agent with low permeability characteristics, into highly deformable bilosomes (HBs) for augmenting its topical delivery. HBs contain edge activator in addition to the constituents of traditional bilosomes (Span 60, cholesterol, and bile salts). More elasticity is provided to the membrane of vesicles by the existence of edge activator and is expected to increase the topical permeation of TCZ. HBs were formulated using ethanol injection technique based on 2<sup>4</sup> complete factorial design to inspect the impact of various formulation variables (bile salt type and amount, edge activator type, and sonication time) on HBs characteristics (entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP)). The optimum formula (HB14) was decided based on Design-Expert<sup>®</sup> software and was utilized for further explorations. HB14 exhibited EE% = 84.25 ± 0.49%, PS = 400.10 ± 1.69 nm, PDI = 0.23 ± 0.01, and ZP = - 56.20 ± 0.00 mV. HB14 showed spherical vesicles with higher deformability index (9.94 ± 1.91 g) compared to traditional bilosomal formula (3.49 ± 0.49 g). Furthermore, HB14 showed superior inhibition of Candida albicans growth relative to TCZ suspension using XTT (2,3-bis(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reduction assay. Moreover, in vivo skin deposition studies revealed superior TCZ deposition inside the skin from HB14 compared to traditional bilosomal formula and TCZ suspension. Moreover, histopathological examination in rats assured the safety of HB14 for topical use. Concisely, the obtained outcomes confirmed the pronounced efficacy of HBs for topical delivery of TCZ.

Said, M., A. A. Aboelwafa, A. H. Elshafeey, and I. Elsayed, Central composite optimization of ocular mucoadhesive cubosomes for enhanced bioavailability and controlled delivery of voriconazole, , vol. 61, pp. 102075, 2021. AbstractWebsite

This study aimed to formulate and statistically optimize cubosomal formulations loaded with voriconazole to enhance and control its ocular bioavailability. The independent variables of the employed central composite face-centered design were the percentages of monoolein and Pluronic F127. Particle size, zeta potential, drug content, entrapment efficiency and drug release parameters were adopted as dependent responses. The conducted factorial analysis resulted in an optimum formulation composed of 15% monoolein and 1.2% Pluronic F127. The optimum cubosomal formulation showed well-dispersed vesicles with a particle size of 160 nm and a relatively high drug loading (0.81%). Then, it was coated with chitosan to further enhance its precorneal residence time. The chitosan-coated formulation showed high mucoadhesive properties, in addition to being safe and biocompatible. Moreover, it showed higher Cmax, Tmax, AUC(0-8), AUC(0-∞), MRT, T1/2 and HVDt50%Cmax when compared to voriconazole suspension. It showed also higher concentration in the vitreous humor when compared to the drug suspension which indicates deeper penetration into the ocular tissue. Finally, the chitosan-coated optimum cubosomal formulation could be considered an efficient ocular nanocarrier for voriconazole.

Fatouh, A. M., A. H. Elshafeey, and A. A. Elbary, Galactosylated Chitosan Coated Liposomes of Ledipasvir for Liver Targeting: Chemical Synthesis, Statistical Optimization, In-vitro and In-vivo evaluation, , vol. 110, issue 3, pp. 1148 - 1159, 2021. AbstractWebsite

Ledipasvir is a novel antiviral agent used in the treatment of hepatitis C. We aim in our study to increase its delivery to hepatocytes and prolong its retention within liver. Several formulae of ledipasvir loaded liposomes were prepared and the best formula regarding particle size, zeta potential, polydispersity index and entrapment efficiency was selected. On the other hand, galactosylated chitosan was synthesized in a chemical reaction. Then the best liposomes formula was coated with the galactosylated chitosan. Having galactose residues on their surface, the coated liposomes can bind to the asialoglycoprotein receptors on the targeted hepatocytes enhancing ledipasvir uptake into them. The galactosylated chitosan coated liposomes had particle size of 218.2 nm ± 7.21, zeta potential of 27.15 mV ± 1.76, polydispersity index of 0.278 ± 0.055 and entrapment efficiency % of 54.63% ± 0.05 respectively. The pharmacokinetic study revealed a significant increase in the liver peak concentration (Cmax) and the area under liver concentration versus time curve AUC(0–72 h) and significant prolongation in the liver terminal half life (t½) and mean residence time (MRT) in comparison to the oral dispersion of ledipasvir with values of 11,400 ng/g, 88,855 ng∗h/g, 32.00 h and 18.11 h respectively.

Fatouh, A. M., A. H. Elshafeey, and A. A. Elbary, Liver targeting of ledipasvir via galactosylated chitosan–coated spanlastics: chemical synthesis, statistical optimization, in vitro, and pharmacokinetic evaluation, , 2021. AbstractWebsite

Ledipasvir is an effective direct acting antiviral agent used in the treatment of hepatitis C virus. The high price of ledipasvir was a reason for its limited provision to wide population of HCV patients.

Elshafeey, A. H., and R. M. El-Dahmy, "Formulation and Development of Oral Fast-Dissolving Films Loaded with Nanosuspension to Augment Paroxetine Bioavailability: In Vitro Characterization, Ex Vivo Permeation, and Pharmacokinetic Evaluation in Healthy Human Volunteers", Pharmaceutics, vol. 13, no. 11, 2021. AbstractWebsite

Paroxetine (PX) is the most potent serotonin reuptake inhibitor utilized in depression and anxiety treatment. It has drawbacks, such as having a very bitter taste, low water solubility, and undergoing extensive first pass metabolism, leading to poor oral bioavailability (<50%). This work aimed to develop and optimize palatable oral fast-dissolving films (OFDFs) loaded with a paroxetine nanosuspension. A PX nanosuspension was prepared to increase the PX solubility and permeability via the buccal mucosa. The OFDFs could increase PX bioavailability due to their rapid dissolution in saliva, without needing water, and the rapid absorption of the loaded drug through the buccal mucosa, thus decreasing the PX metabolism in the liver. OFDFs also offer better convenience to patients with mental illness, as well as pediatric, elderly, and developmentally disabled patients. The PX nanosuspension was characterized by particle size, poly dispersity index, and zeta potential. Twelve OFDFs were formulated using a solvent casting technique. A 22 × 31 full factorial design was applied to choose the optimized OFDF, utilizing Design-Expert® software (Stat-Ease Inc., Minneapolis, MN, USA). The optimized OFDF (F1) had a 3.89 ± 0.19 Mpa tensile strength, 53.08 ± 1.28% elongation%, 8.12 ± 0.13 MPa Young’s modulus, 17.09 ± 1.30 s disintegration time, and 96.02 ± 3.46% PX dissolved after 10 min. This optimized OFDF was subjected to in vitro dissolution, ex vivo permeation, stability, and palatability studies. The permeation study, using chicken buccal pouch, revealed increased drug permeation from the optimized OFDF; with a more than three-fold increase in permeation over the pure drug. The relative bioavailability of the optimized OFDF in comparison with the market tablet was estimated clinically in healthy human volunteers and was found to be 178.43%. These findings confirmed the success of the OFDFs loaded with PX nanosuspension for increasing PX bioavailability.

Abdelbari, M. A., S. S. El-Mancy, A. H. Elshafeey, and A. A. Abdelbary, "Implementing spanlastics for improving the ocular delivery of clotrimazole: In vitro characterization, ex vivo permeability, microbiological assessment and in vivo safety study", International Journal of Nanomedicine, vol. 16, 2021. Abstract

{Purpose: The aim of this study was to encapsulate clotrimazole (CLT), an antifungal drug with poor water solubility characteristics, into spanlastics (SPs) to provide a controlled ocular delivery of the drug. Methods: Span 60 was used in the formulation of SPs with Tween 80, Pluronic F127, or Kolliphor RH40 as an edge activator (EA). The presence of EA offers more elasticity to the membrane of the vesicles which is expected to increase the corneal permeation of CLT. SPs were prepared using ethanol injection method applying 32 complete factorial design to study the effect of formulation variables (ratio of Span 60: EA (w/w) and type of EA) on SPs characteristics (encapsulation efficiency percent (EE%), average vesicle size (VS), polydis-persity index (PDI) and zeta potential (ZP)). Design-Expert software was used to determine the optimum formulation for further investigations. Results: The optimum formulation determined was S1, which contains 20 mg of Tween 80 used as an EA and 80 mg of Span 60. S1 exhibited EE% = 66.54 ± 7.57%

El-Dahmy, R. M., A. H. Elshafeey, N. A. A. E. Gawad, O. N. El-Gazayerly, and I. Elsayed, "Statistical optimization of nanostructured gels for enhancement of vinpocetine transnasal and transdermal permeation", Journal of Drug Delivery Science and Technology, vol. 66, pp. 102871, 2021. AbstractWebsite

Pluronic-based nanostructured gels were developed and optimized to increase the permeability of vinpocetine through the skin and the mucous layer of the nasal cavity. A modified thin-film hydration technique was utilized to prepare the nanostructured gel formulae containing different concentrations of Pluronic F127, Pluronic F68 and oleic acid. The formed nanodispersions were tested for their pH, particle size, zeta potential, polydispersity index, entrapment efficiency and gelation temperature. Box-Behnken statistical design was used to choose the optimized nasal and transdermal nanostructured gel formulae utilizing Design-Expert® software. The nasal optimized formula consisted of 2.4% oleic acid, 23.46% total surfactants and 27.13% Pluronic F68, had a gelation temperature of 35 °C which could be suitable to form in situ gel upon application into the nasal cavity. On the other hand, the transdermal optimized formula, composed of 1.77% oleic acid, 22.46% total surfactants and 11.54% Pluronic F68, formed gel at room temperature that could be suitable to be applied onto the skin. The optimized gel formulae were investigated for their in vitro drug release, rheology, morphology, histopathology and ex vivo permeation. The extent of drug permeated from the optimized formula through both nasal and skin membranes was significantly increased by 3.39 and 4.7 folds when compared to the drug suspension. Finally, the obtained findings ensured the creditable impact of the nanostructured gels as promising nanocarriers for enhancing transmucosal and transdermal vinpocetine permeation.

Elshafeey, A. H., A. A. Abdelbary, S. Mosallam, M. H. Ragaie, and N. H. Moftah, "Use of Novasomes as a Vesicular Carrier for Improving the Topical Delivery of Terconazole: In Vitro Characterization, In Vivo Assessment and Exploratory Clinical Experimentation", International Journal of Nanomedicine, vol. 16, pp. 119-132, 2021. Use of Novasomes as a Vesicular Carrier .pdf
2020
Elsenosy, F. M., G. A. Abdelbary, A. H. Elshafeey, I. Elsayed, and A. R. Fares, "Brain targeting of duloxetine hcl via intranasal delivery of loaded cubosomal gel: In vitro characterization, ex vivo permeation, and in vivo biodistribution studies", International Journal of Nanomedicine, vol. 15, pp. 9517 - 9537, 2020. AbstractWebsite
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El-Nabarawi, M. A., A. H. Elshafeey, D. M. Mahmoud, and A. M. El Sisi, Fabrication, optimization, and in vitro/in vivo evaluation of diclofenac epolamine flash tablet, , vol. 10, issue 5, pp. 1314 - 1326, 2020. AbstractWebsite

The objective of this work was to design a diclofenac epolamine (DE) flash tablets (FTs) intended to dissolve in the mouth saliva, thereby improving the DE bioavailability and reducing its first-pass liver metabolism. Design-Expert software was used to build a 31.22 full factorial design (12 runs). FTs were fabricated using lyophilization process. The dissolution response was selected to pick the optimized run. The results indicate that the optimized run (R1) showed the fastest drug dissolution (total dissolution in 12 min). The predicted run (Rp) showed a desirability of about 0.93. Differential scanning calorimetry(DSC) analysis results showed a decrease in the drug melting point of the R1 formulation. Fourier–transform infrared spectroscopy (FTIR) showed the compatibility of the drug with other components of formulation, X-ray powder diffraction (XRPD) analysis showed the evolution of the drug physical state from a crystalline to an amorphous form and scanning electron microscopy(SEM) divugled the disappearance of drug crystals in gelatin strands. The results of the pharmacokinetic study performed in 6 human volunteers evidenced an increase in the maximum DE concentration in plasma and, consequently, an increased bioavailability of the FT formulation as compared with a reference formulation(Fr). Concisely, the developed FTs (R1) showed promising results which could be able to enhance oral bioavailability, reduce the therapeutic dose of the drug, and abate of the complications accompanied with conventional dosage forms.

Elsayed, I., R. M. El-Dahmy, S. Z. El-Emam, A. H. Elshafeey, N. A. A. E. Gawad, and O. N. El-Gazayerly, Response surface optimization of biocompatible elastic nanovesicles loaded with rosuvastatin calcium: enhanced bioavailability and anticancer efficacy, , vol. 10, issue 5, pp. 1459 - 1475, 2020. AbstractWebsite

Statins are mainly used for the treatment of hyperlipidemia, but recently, their anticancer role was extremely investigated. The goal of this study was to statistically optimize novel elastic nanovesicles containing rosuvastatin calcium to improve its transdermal permeability, bioavailability, and anticancer effect. The elastic nanovesicles were composed of Tween® 80, cetyl alcohol, and clove oil. The nanodispersions were investigated for their entrapment efficiency, particle size, zeta potential, polydispersity index, and elasticity. The optimized elastic nanovesicular dispersion is composed of 20% cetyl alcohol, 53.47% Tween 80, and 26.53% clove oil. Carboxy methylcellulose was utilized to convert the optimized elastic nanovesicular dispersion into elastic nanovesicular gels. Both the optimized dispersion and the optimized gel (containing 2% w/v carboxymethylcellulose) were subjected to in vitro release study, scanning and transmission electron microscopy, histopathological evaluation, and ex vivo permeation. The cell viability assay of the optimized gel on MCF-7 and Hela cell lines showed significant antiproliferative and potent cytotoxic effects when compared to the drug gel. Moreover, the optimized gel accomplished a significant increase in rosuvastatin bioavailability upon comparison with the drug gel. The optimized gel could be considered as a promising nanocarrier for statins transdermal delivery to increase their systemic bioavailability and anticancer effect.

Joseph Naguib, M., A. Moustafa Kamel, A. Thabet Negmeldin, A. H. Elshafeey, and I. Elsayed, "Molecular docking and statistical optimization of taurocholate-stabilized galactose anchored bilosomes for the enhancement of sofosbuvir absorption and hepatic relative targeting efficiency", Drug Delivery, vol. 27, no. 1, pp. 996-1009, 2020. AbstractWebsite
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Elshafeey, A. H., R. Zayed, M. H. Shukr, and I. Elsayed, "Sucrose acetate isobutyrate based nanovesicles: A promising platform for drug delivery and bioavailability enhancement", Journal of Drug Delivery Science and Technology, vol. 58, 2020. AbstractWebsite
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2019
Elshafeey, A. H., M. H. Shukr, and A. M. E. Sharawy, "Optimization and in vivo evaluation of duloxetine hydrochloride buccoadhesive lyophilized tablets", Journal of Drug Delivery Science and Technology, vol. 52, pp. 282-291, 2019. journal_of_drug_delivery_science_and_technology.pdf
Elsayed, I., R. M. El-Dahmy, A. H. Elshafeey, N. A. A. El Gawad, and O. N. El Gazayerly, "Tripling the bioavailability of rosuvastatin calcium through development and optimization of an in-situ forming nanovesicular system", Pharmaceutics, vol. 11, no. 6, 2019. AbstractWebsite
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2018
Said, M., I. Elsayed, A. A. Aboelwafa, and A. H. Elshafeey, "A novel concept of overcoming the skin barrier using augmented liquid nanocrystals: Box-Behnken optimization, ex vivo and in vivo evaluation", Colloids and Surfaces B: Biointerfaces, vol. 170, pp. 258-265, 2018. AbstractWebsite
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Yousry, C., M. M. Amin, A. H. Elshafeey, and O. N. El Gazayerly, "Ultrahigh verapamil-loaded controlled release polymeric beads using superamphiphobic substrate: D-optimal statistical design, in vitro and in vivo performance", Drug Delivery, vol. 25, no. 1, pp. 1448-1460, 2018. AbstractWebsite
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2017
Abdelrahman, F. E., I. Elsayed, M. K. Gad, A. H. Elshafeey, and M. I. Mohamed, "{Response surface optimization, Ex vivo and In vivo investigation of nasal spanlastics for bioavailability enhancement and brain targeting of risperidone}", {INTERNATIONAL JOURNAL OF PHARMACEUTICS}, vol. {530}, no. {1-2}, pp. {1-11}, {SEP 15}, 2017. Abstract

{Transnasal brain drug targeting could ensure better drug delivery to the brain through the olfactory pathway. Risperidone bioavailability is 66% in extensive metabolizers and 82% in slow metabolizers. The aim of this study is to investigate the ability of the nanovesicular spanlastics to effectively deliver risperidone through the nasal route to the brain and increase its bioavailability. Spanlastics formulae, composed of span and polyvinyl alcohol, were designed based on central composite statistical design. The planned formulae were prepared using ethanol injection method. The prepared formulae were characterized by testing their particle size, polydispersity index, zeta potential and encapsulation efficiency. The optimized formula having the lowest particle size, polydispersity index, the highest zeta potential and encapsulation efficiency was subjected to further investigations including characterization of its rheological properties, elasticity, transmission electron microscopy, in vitro diffusion, ex vivo permeation, histopathology and in vivo biodistribution. The optimized formula was composed of 5 mg/mL span and 30 mg/mL polyvinyl alcohol. It showed significantly higher transnasal permeation and better distribution to the brain, when compared to the used control regarding the brain targeting efficiency and the drug transport percentage (2.16 and 1.43 folds increase, respectively). The study introduced a successful and promising formula to directly and effectively carry the drug from nose to brain. (C) 2017 Elsevier B.V. All rights reserved.}

Fatouh, A. M., A. H. Elshafeey, and A. A. Elbary, "Intranasal agomelatine solid lipid nanoparticles to enhance brain delivery: formulation, optimization and in vivo pharmacokinetics", Drug Design, Development and Therapy, vol. 11: Dove Medical Press, pp. 1815 - 1825, 2017/06/19. AbstractWebsite

PURPOSE: Agomelatine is a novel antidepressant drug suffering from an extensive first-pass metabolism leading to a diminished absolute bioavailability. The aim of the study is: first to enhance its absolute bioavailability, and second to increase its brain delivery. METHODS: To achieve these aims, the nasal route was adopted to exploit first its avoidance of the hepatic first-pass metabolism to increase the absolute bioavailability, and second the direct nose-to-brain pathway to enhance the brain drug delivery. Solid lipid nanoparticles were selected as a drug delivery system to enhance agomelatine permeability across the blood–brain barrier and therefore its brain delivery. RESULTS: The optimum solid lipid nanoparticles have a particle size of 167.70 nm ±0.42, zeta potential of −17.90 mV ±2.70, polydispersity index of 0.12±0.10, entrapment efficiency % of 91.25%±1.70%, the percentage released after 1 h of 35.40%±1.13% and the percentage released after 8 h of 80.87%±5.16%. The pharmacokinetic study of the optimized solid lipid nanoparticles revealed a significant increase in each of the plasma peak concentration, the AUC(0–360 min) and the absolute bioavailability compared to that of the oral suspension of Valdoxan(®) with the values of 759.00 ng/mL, 7,805.69 ng⋅min/mL and 44.44%, respectively. The optimized solid lipid nanoparticles gave a drug-targeting efficiency of 190.02, which revealed more successful brain targeting by the intranasal route compared with the intravenous route. The optimized solid lipid nanoparticles had a direct transport percentage of 47.37, which indicates a significant contribution of the direct nose-to-brain pathway in the brain drug delivery. CONCLUSION: The intranasal administration of agomelatine solid lipid nanoparticles has effectively enhanced both the absolute bioavailability and the brain delivery of agomelatine.

Fatouh, A. M., A. H. Elshafeey, and A. A. Elbary, "Agomelatine-based in situ gels for brain targeting via the nasal route: statistical optimization, in vitro, and in vivo evaluation", Drug Delivery, vol. 24, issue 1: Taylor & Francis, pp. 1077 - 1085, 2017. AbstractWebsite

AbstractAgomelatine (AGM) is an antidepressant drug with a low absolute bioavailability due to the hepatic first pass metabolism. AGM-loaded solid lipid nanoparticles were formulated in the form of an in situ gel to prolong the intranasal retention time and subsequently to increase the absorbed amount of AGM. The optimized in situ gel formula had a sol?gel transition temperature of 31?°C?±?1.40, mucociliary transport time of 27?min ±1.41%, released after 1 and 8?h of 46.3%?±?0.85 and 70.90%?±?1.48. The pharmacokinetic study of the optimized in situ gel revealed a significant increase in the peak plasma concentration, area under plasma concentration versus time curve and absolute bioavailability compared to that of the oral suspension of Valdoxan? with the values of 247?±?64.40?ng/mL, 6677.41?±?1996?ng.min/mL, and 37.89%, respectively. It also gave drug targeting efficiency index of 141.42 which revealed more successful brain targeting by the intranasal route compared to the intravenous route and it had direct transport percent index of 29.29 which indicated a significant contribution of the direct nose to brain pathway in the brain drug delivery.

Eissa, I. H., H. Mohammad, O. A. Qassem, W. Younis, T. M. Abdelghany, A. Elshafeey, M. M. Abd Rabo Moustafa, M. N. Seleem, and A. S. Mayhoub, Diphenylurea derivatives for combating methicillin- and vancomycin-resistant Staphylococcus aureus, , vol. 130, issue Supplement C, pp. 73 - 85, 2017. AbstractWebsite

AbstractA new class of diphenylurea was identified as a novel antibacterial scaffold with an antibacterial spectrum that includes highly resistant staphylococcal isolates, namely methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA & VRSA). Starting with a lead compound 3 that carries an aminoguanidine functionality from one side and a n-butyl moiety on the other ring, several analogues were prepared. Considering the pharmacokinetic parameters as a key factor in structural optimization, the structure-activity-relationships (SARs) at the lipophilic side chain were rigorously examined leading to the discovery of the cycloheptyloxyl analogue 21n as a potential drug-candidate. This compound has several notable advantages over vancomycin and linezolid including rapid killing kinetics against MRSA and the ability to target and reduce the burden of MRSA harboring inside immune cells (macrophages). Furthermore, the potent anti-MRSA activity of 21n was confirmed in vivo using a Caenorhabditis elegans animal model. The present study provides a foundation for further development of diphenylurea compounds as potential therapeutic agents to address the burgeoning challenge of bacterial resistance to antibiotics.

Morsi, N. M., G. A. Abdelbary, A. H. Elshafeey, and A. M. Ahmed, "Engineering of a novel optimized platform for sublingual delivery with novel characterization tools: in vitro evaluation and in vivo pharmacokinetics study in human", Drug Delivery, vol. 24, issue 1: Taylor & Francis, pp. 918 - 931, 2017. AbstractWebsite

AbstractThe aim of this work was to develop a novel and more efficient platform for sublingual drug delivery using mosapride citrate (MSP) as a model drug. The engineering of this delivery system had two stages, the first stage was tuning of MSP physicochemical properties by complexation with pure phosphatidylcholine or phosphatidylinositol enriched soybean lecithin to form MSP-phospholipid complex (MSP-PLCP). Changes in physicochemical properties were assessed and the optimum MSP-PLCP formula was then used for formulation into a flushing resistant platform using two mucoadhesive polymers; sodium alginates and sodium carboxymethylcellulose at different concentrations. Design of experiment approach was used to characterize and optimize the formulated flushing resistant platform. The optimized formulation was then used in a comparative pharmacokinetics study with the market formulation in human volunteers. Results showed a marked change in MSP physicochemical properties of MSP-PLCP compared to MSP. Addition of mucoadhesive polymers to flushing resistant platform at an optimum concentration balanced between desired mucoadhesive properties and a reasonable drug release rate. The optimized formulation showed significantly a superior bioavailability in humans when compared to the market sublingual product. Finally, the novel developed sublingual flushing resistant platform offers a very promising and efficient tool to extend the use of sublingual route and widen its applications.

Sharawy, A. M. E., M. H. Shukr, and A. H. Elshafeey, "Formulation and optimization of duloxetine hydrochloride buccal films: in vitro and in vivo evaluation", Drug Delivery, vol. 24, no. 1: Taylor & Francis, pp. 1762-1769, 2017. AbstractWebsite

AbstractDuloxetine hydrochloride (DH) is a serotonin–norepinephrine reuptake inhibitor (SSNRI) indicated for the treatment of depression. Duloxetine suffers from reduced oral bioavailability (≈50%) due to hepatic metabolism. This study aims to develop DH buccoadhesive films to improve its bioavailability. DH buccoadhesive films were prepared adopting the solvent casting method using hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA). The prepared films were evaluated for weight uniformity, drug content, surface pH, swelling index, mucoadhesion strength and drug release percentages. Accelerated stability and bioavailability studies in healthy human volunteers were also performed for the selected films. Results of the evaluation tests showed that the optimum physicochemical characters were obtained by the films prepared with 2% HPMC using 10% propylene glycol (F2 films). Accelerated stability studies revealed that DH showed proved stability throughout the experiment time. DH bioavailability from F2 films was determined and compared with that of the marketed oral capsules (Cymbalta® 30 mg). The pharmacokinetic results showed that Cmax for F2 was higher than the market product. In addition, ANOVA analysis showed that a Tmax of F2 film was significantly lower, while, the AUC0–72 of F2 was significantly higher than that of Cymbalta capsules. The percentage relative bioavailability of DH from F2 was found to be 296.39%. Therefore, the prepared buccal films offer an alternative route for the administration of DH with the possibility of improving its bioavailability.