Badr-Eldin, S. M., H. M. Aldawsari, A. Hanafy, M. S. Abdlmoneim, S. Abdel-Hady, and A. Hassan, "Enhanced Hepatoprotective Effect of Adansonia Digitata Extract on Paracetamol-Induced Hepatotoxicity", Res J Pharm Biol Chem Sci , vol. 8, issue 6, pp. 787-794, 2017.
Ahmed, O. A. A., S. M. Badr-Eldin, and T. A. Ahmed, "Kinetic study of the in vitro release and stability of theophylline floating beads", Int J Pharm Pharm Sci, vol. 5, issue 1, pp. 1-6, 2013.
Ahmed, O. A. A., and S. M. Badr-Eldin, "Development of an optimized avanafil-loaded invasomal transdermal film: Ex vivo skin permeation and in vivo evaluation.", International journal of pharmaceutics, vol. 570, pp. 118657, 2019. Abstract

Avanafil (AVA) is a recent FDA approved selective phosphodiesterase type 5 inhibitor used for oral treatment of erectile dysfunction. The oral bioavailability of the drug is challenged by its reduced water solubility, considerable presystemic metabolism, and altered absorption in the presence of food. Accordingly, this work aimed to surmount the aforementioned challenges through the development of optimized nanosized AVA invasomes with enhanced transdermal delivery. AVA invasomes were prepared according to a Box-Behnken experimental design to explore the impact of the following formulation factors: phospholipid % (X), ethanol % (X), terpene % (X), and terpene type (X) on vesicle size (Y) and entrapment efficiency (Y). The three numerical variables were used at three levels, while the categorical variable was used at two levels. The optimized formulation with vesicular size of 109.92 nm and entrapment efficiency of 96.98% was incorporated into a hydroxypropyl methyl cellulose-based transdermal film and characterized for its ex vivo permeation behavior and in vivo performance in rats. The optimized AVA invasomal film showed enhanced ex vivo permeation with an enhancement factor of 2.514 and a more than four-fold increase in relative bioavailability compared to the raw AVA film. These results provide insight into the capability of the optimized invasomal film to enhance the transdermal permeation and bioavailability of AVA.

Badr-Eldin, S. M., G. S. Labib, and M. H. Aburahma, "Eco-Friendly Tadalafil Surfactant-Free Dry Emulsion Tablets (SFDETs) Stabilized by In Situ Self-Assembled Aggregates of Natural Oil and Native Cyclodextrins.", AAPS PharmSciTech, vol. 20, issue 7, pp. 255, 2019. Abstract

The main principles of green chemistry and engineering were extended to pharmaceutical formulations to prepare eco-friendly surfactant-free dry emulsion tablets (SFDETs) devoid of solvents or synthetic surfactants. Surfactant-free emulsions were stabilized by in situ cyclodextrins/sweet almond oil inclusion complexes and assessed for creaming stability. Formulation variables' effects on the emulsion droplet size and tadalafil solubility were studied using 2 × 3 factorial design. The emulsions exhibited nanometric and micrometric droplet sizes. The optimized nanoemulsion was loaded with tadalafil, morphologically evaluated, and utilized for preparing lyophilized SFDETs using different gelatin/Pearlitol® ratios. The tablets were characterized and the selected formulation was subjected to storage for 6 months. The emulsions prepared using β-cyclodextrin or higher concentrations of α-cyclodextrin showed little or no phase separation. Statistical analysis revealed significant influence of cyclodextrin type and amount on droplet size, while cyclodextrin type and oil volume exhibited significant effect on drug solubility. Morphological examination revealed non-aggregated spherical emulsion droplets. The prepared tablets showed satisfactory mechanical strength, short disintegration times, and enhanced drug dissolution. The selected tablet formulation (gelatin/Pearlitol®, 4:2 w/w) showed acceptable stability at 25°C/60% relative humidity. An overall conclusion claims that the absence of surfactants is expected to minimize the proposed tablets' in vivo toxicity and environmental concerns.

Badr-Eldin, S. M., S. A. Elkheshen, and M. M. Ghorab, "Improving tadalafil dissolution via surfactant-enriched tablets approach: Statistical optimization, characterization, and pharmacokinetic assessment", Journal of Drug delivery Science and Technology, vol. 41, pp. 197-205, 2017. AbstractWebsite

Tadalafil suffers from poor aqueous solubility that could lead to fluctuating blood levels and unreproducible effect. Thus, this work aimed at improving tadalafil dissolution utilizing the approach of surfactant-enriched tablets. The feasibility of minimizing various surfactants quantities was investigated by establishing the ratio of the surfactant to drug that is required for drug solubilization in micellar solutions. Based on the computed ratios, Tween was precluded from formulation studies due to its poor solubilizing capacity towards the drug. 23 factorial design was employed to assess the impact of formulation attributes on tablets' characteristics. Based on the statistical analysis and the desirability function approach, tablet formulation F6 prepared using CTAB, Avicel PH 102, and 5% Ac-Di-Sol was selected as the optimum formulation. The selected formulation showed adequate stability after storage at 40 °C and 75% R.H. for twelve weeks. Pharmacokinetic study revealed that the selected surfactant-enriched tablet formulation F6 showed enhanced bioavailability compared to the market product Cialis®.

Ahmed, O. A. A., K. M. El-Say, B. M. Aljaeid, S. M. Badr-Eldin, and T. A. Ahmed, "Optimized vinpocetine-loaded vitamin E D-α-tocopherol polyethylene glycol 1000 succinate-alpha lipoic acid micelles as a potential transdermal drug delivery system: in vitro and ex vivo studies.", International journal of nanomedicine, vol. 14, pp. 33-43, 2019. AbstractWebsite

Background: Vinpocetine (VNP), a semisynthetic natural product, is used as a vasodilator for cerebrovascular and age-related memory disorders. VNP suffers from low oral bioavailability owing to its low water solubility and extensive first-pass metabolism. This work aimed at utilizing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and alpha lipoic acid (ALA) to develop efficient micellar system for transdermal delivery of VNP.

Materials and methods: VNP-TPGS-ALA micelles were prepared, characterized for particle size using particle size analyzer, and investigated for structure using transmission electron microscope. Optimization of VNP-TPGS-ALA micelles-loaded transdermal films was performed using Box-Behnken experimental design. The investigated factors were percentage of ALA in TPGS (X), citral concentration (X), and propylene glycol concentration (X). Elongation percent (Y), initial permeation after 2 hours (Y), and cumulative permeation after 24 hours (Y) were studied as responses.

Results: Statistical analysis revealed optimum levels of 16.62%, 3%, and 2.18% for X, X, and X, respectively. Fluorescent laser microscopic visualization of skin penetration of the optimized transdermal film revealed marked widespread fluorescence intensity in skin tissue after 0.5, 2, and 4 hours compared with raw VNP transdermal film formulation, which indicated enhancement of VNP skin penetration.

Conclusion: The obtained results highlighted the potentiality of VNP nanostructure-based films for controlling the transdermal permeation of the drug and improving its effectiveness.

Ahmed, T. A., S. M. Badr-Eldin, O. A. A. Ahmed, and H. Aldawsari, "Intranasal optimized solid lipid nanoparticles loaded in situ gel for enhancing trans-mucosal delivery of simvastatin", Journal of Drug Delivery Science and Technology , vol. 48, pp. 499-508, 2018. AbstractWebsite

The aim of this study was to develop optimized simvastatin (SMV) solid lipid nanoparticles (SLNs) with subsequent loading into a thermosensitive in situ gel (ISG) to enhance and control intranasal drug permeation. Three formulation factors were optimized for their effect on particle size and entrapment efficiency (EE). SLNs components were studied thru solid-state characterization. The optimized formulation was morphologically characterized and loaded into poloxamer ISG formulations of different concentrations. Evaluations were done for gelation temperature, viscosity, muco-adhesion strength, and in vitro and ex vivo permeations. Transport across nasal mucosal layers was characterized using a fluorescence laser microscope. The studied factors significantly affected particle size and EE. The drug was successfully encapsulated and homogenously dispersed in the lipid matrix and changed from a crystalline to amorphous state in the optimized SLNs. Transmission electron microscope illustrated the presence of nanoparticles, while scanning electron microscope observations indicated fusion of the particles. An ISG formulation containing 22% poloxamer loaded with optimized SLNs exhibited better mucoadhesion and ex vivo drug permeation, and was able to penetrate deeper into the nasal tissue when compared to the same formulation loaded with pure drug. No signs of inflammation or necrosis were observed upon histopathological study. In summary, this thermosensitive ISG formulation containing SMV SLNs can be considered as an alternative to currently available oral drug formulations, however, further pre/clinical studies are needed.

Darwesh, B., H. M. Aldawsari, and S. M. Badr-Eldin, "Optimized Chitosan/Anion Polyelectrolyte Complex Based Inserts for Vaginal Delivery of Fluconazole: In Vitro/In Vivo Evaluation.", Pharmaceutics, vol. 10, issue 4, 2018 Nov 12. AbstractWebsite

(1) Background: Fluconazole, used orally for vaginal candidiasis, has reported gastrointestinal side effects. Therefore, researchers directed towards the drug vaginal delivery. However, vaginal delivery is limited by poor retention and leakage. Thus, this work aimed at exploring chitosan/anion polyelectrolyte complex (PEC) for the formulation of fluconazole vaginal inserts with controlled release and appreciable mucoadhesion. (2) Methods: PECs were prepared and assessed for interactions. Fluconazole PEC based vaginal inserts were prepared by lyophilization using mannitol. 3¹5¹ factorial design was applied to investigate the effect of the anion type and Chitosan/anion ratio on the inserts mucoadhesion and release properties. The optimized insert [based on 5:5 chitosan: anionic polymer (sodium alginate)] release was modulated by the release retardant; Compritol 888. The selected formulation was subjected to microbiological and histological evaluation. (3) Results: Fluconazole inserts showed satisfactory drug content, acceptable friability percentages and highest swelling indices at six hours. Statistical analysis showed significant effect of the studied factors on detachment force and release properties. Microbiological assays revealed significantly higher antifungal activity of inserts compared to fluconazole solution. Reduced inflammatory cells were confirmed by histological evaluation. (4) Conclusion: CH/Alg based vaginal insert could be a promising platform for vaginal delivery of antifungal drugs used for vaginal candidiasis treatment.

Ahmed, O. A. A., and S. M. Badr-Eldin, "In situ misemgel as a multifunctional dual-absorption platform for nasal delivery of raloxifene hydrochloride: formulation, characterization, and in vivo performance.", International journal of nanomedicine, vol. 13, pp. 6325-6335, 2018. AbstractWebsite

Background: Raloxifene hydrochloride (RLX) is approved by the US Food and Drug Administration for the treatment and prevention of osteoporosis, in addition to reducing the risk of breast cancer in postmenopausal women. RLX has the disadvantages of low aqueous solubility, extensive presystemic intestinal glucuronidation, and first-pass metabolism, resulting in a limited bio-availability of only 2%. The aim of this work was to enhance the bioavailability of RLX via the formulation of an in situ nasal matrix (misemgel) comprising micelles made of vitamin E and D-α-tocopheryl polyethylene glycol 1000 succinate and nanosized self-emulsifying systems (NSEMS).

Materials and methods: Optimization of the RLX-loaded NSEMS was performed using a mixture design. The formulations were characterized by particle size and then incorporated into an in situ nasal gel. Transmission electron microscopy, bovine nasal mucosa ex vivo permeation, and visualization using a fluorescence laser microscope were carried out on the RLX in situ misemgel comparing with raw RLX in situ gel. In addition, the in vivo performance was studied in rats.

Results: The results revealed improved permeation parameters for RLX misemgel compared with control gel, with an enhancement factor of 2.4. In vivo studies revealed a 4.79- and 13.42-fold increased bioavailability for RLX in situ misemgel compared with control RLX in situ gel and commercially available tablets, respectively. The obtained results highlighted the efficacy of combining two different formulations to enhance drug delivery and the benefits of utilizing different possible paths for drug absorption.

Conclusion: The developed in situ misemgel matrix could be considered as a promising multifunctional platform for nasal delivery which works based on a dual-absorption mechanism.

Badr-Eldin, S. M., and O. A. Ahmed, "Optimized nano-transfersomal films for enhanced sildenafil citrate transdermal delivery: ex vivo and in vivo evaluation.", Drug design, development and therapy, vol. 10, pp. 1323-33, 2016. AbstractWebsite

Sildenafil citrate (SLD) is a selective cyclic guanosine monophosphate-specific phosphodiesterase type 5 inhibitor used for the oral treatment of erectile dysfunction and, more recently, for other indications, including pulmonary hypertension. The challenges facing the oral administration of the drug include poor bioavailability and short duration of action that requires frequent administration. Thus, the objective of this work is to formulate optimized SLD nano-transfersomal transdermal films with enhanced and controlled permeation aiming at surmounting the previously mentioned challenges and hence improving the drug bioavailability. SLD nano-transfersomes were prepared using modified lipid hydration technique. Central composite design was applied for the optimization of SLD nano-transfersomes with minimized vesicular size. The independent variables studied were drug-to-phospholipid molar ratio, surfactant hydrophilic lipophilic balance, and hydration medium pH. The optimized SLD nano-transfersomes were developed and evaluated for vesicular size and morphology and then incorporated into hydroxypropyl methyl cellulose transdermal films. The optimized transfersomes were unilamellar and spherical in shape with vesicular size of 130 nm. The optimized SLD nano-transfersomal films exhibited enhanced ex vivo permeation parameters with controlled profile compared to SLD control films. Furthermore, enhanced bioavailability and extended absorption were demonstrated by SLD nano-transfersomal films as reflected by their significantly higher maximum plasma concentration (C max) and area under the curve and longer time to maxi mum plasma concentration (T max) compared to control films. These results highlighted the potentiality of optimized SLD nano-transfersomal films to enhance the transdermal permeation and the bioavailability of the drug with the possible consequence of reducing the dose and administration frequency.

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