Othman, A. I., M. M. Amin, S. K. Abu-Elyazid, and G. A. Abdelbary, "Trimetazidine Dihydrochloride Pulsatile-Release Tablets for the Treatment of Morning Anginal Symptoms: Dual Optimization, Characterization and Pharmacokinetic Evaluation.", Current drug delivery, vol. 18, issue 8, pp. 1182-1196, 2021. Abstract

OBJECTIVE: This research work aimed to target the early morning peak symptoms of chronic stable angina through formulating antianginal drug, Trimetazidine (TMZ) in a pulsatile-release tablet.

METHODS: The core formulae were optimized using 22 .31 factorial design to minimize disintegration time (DT) and maximize drug release after 5 minutes (Q5min). Different ratios of Eudragit S100 and Eudragit L100 were used as a coating mixture for the selected core with or without a second coating layer of hydroxypropyl methylcellulose (HPMC E50). The different formulation variables were statistically optimized for their effect on lag time and drug release after 7 hours (Q7h) using BoxBehnken design. The optimized formula (PO) was subjected to stability study and pharmacokinetic assessment on New Zealand rabbits.

RESULTS: The optimal core (F8) was found to have 1.76 min disintegration time and 61.45% Q5min PO showed a lag time of 6.17 h with 94.80% Q7h and retained good stability over three months. The pharmacokinetics study confirmed the pulsatile-release pattern with Cmax of 206.19 ng/ml at 5.33 h (Tmax) and 95.85% relative bioavailability compared to TMZ solution.

CONCLUSION: Overall pulsatile-release tablets of TMZ successfully released the drug after a desirable lag time, providing a promising approach for early morning anginal symptoms relief.

El-Halim, S. M. A., G. A. Abdelbary, M. M. Amin, M. Y. Zakaria, H. A. Shamsel-Din, and ahmed b ibrahim, "Stabilized oral nanostructured lipid carriers of Adefovir Dipivoxil as a potential liver targeting: Estimation of liver function panel and uptake following intravenous injection of radioiodinated indicator", DARU Journal of Pharmaceutical Sciences, vol. 28, pp. 517-532, 2020.
Abdelbary, G. A., O. M. Khowessah, and A. - H. A. Bakr, "Potential treatment of arthritis with an optimized Mometasone Furoate loaded-ethosomal gel in carrageenan-induced rat joint arthritis", Journal of Drug Delivery Science and Technology, vol. 57, pp. 101771, 2020.
Abdelbary, G. A., M. M. Amin, M. Y. Zakaria, and S. A. El Awdan, "Adefovir dipivoxil loaded proliposomal powders with improved hepatoprotective activity: formulation, optimization, pharmacokinetic, and biodistribution studies.", Journal of liposome research, vol. 28, issue 4, pp. 259-274, 2017 Aug 24, 2018. Abstract

The present study aimed to prepare proliposomal formulae for improving the oral bioavailability of adefovir dipivoxil (AD), a nucleoside reverse transcriptase inhibitor effective against hepatitis B virus (HBV). The prepared proliposomal formulae were characterized for entrapment efficiency (E.E.%), vesicle size and in vitro drug release after reconstitution to conventional liposomes. The optimized formula (F9) with a maximum desirability value of 0.858 was selected having E.E.% of 71 ± 3.3% with an average vesicle size of 164.6 ± 5 nm. Moreover, the crystallization of AD within the optimized formula investigated via powder X-ray diffraction (XRD) and differential scanning calorimetry (DSC) confirmed the presence of the drug in an amorphous state within the lipid vesicles with enhanced stability over a storage period of 12 months. Thioacetamide-induced liver damage in rats evidenced by elevated liver enzymes was significantly improved after treatment with the optimum formula. Pharmacokinetic and biodistribution studies of formula F9 showed a higher accumulation of AD in the liver with enhanced bioavailability compared to AD suspension which highlights its potential advantage for an effective treatment of chronic HBV. Hence, proliposomal drug delivery is considered as a better choice for the oral delivery of AD.

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, pp. 918-931, 2017 Nov. Abstract

The 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.

Abdelbary, G. A., M. M. Amin, and M. Y. Zakaria, "Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies.", Drug delivery, vol. 24, issue 1, pp. 309-319, 2017 Nov. Abstract

CONTEXT: Vesicular drug carriers for ocular delivery have gained a real potential. Proniosomal gels as ocular drug carriers have been proven to be an effective way to improve bioavailability and patient compliance.

OBJECTIVE: Formulation and in vitro/ex vivo/in vivo characterization of ketoconazole (KET)-loaded proniosomal gels for the treatment of ocular keratitis.

MATERIALS AND METHODS: The effect of formulation variables; HLB value, type and concentration of non-ionic surfactants (Tweens, Spans, Brijs and Pluronics) with or without lecithin on the entrapment efficiency (EE%), vesicle size and in vitro KET release was evaluated. An ex vivo corneal permeation study to determine the level of KET in the external eye tissue of albino rabbits and an in vivo assessment of the level of KET in the aqueous humors were performed.

RESULTS AND DISCUSSION: In vivo evaluation showed an increase in bioavailability up to 20-folds from the optimum KET proniosomal gel formula in the aqueous humor compared to drug suspension (KET-SP). The selected formulae were composed of spans being hydrophobic suggesting the potential use of a more hydrophobic surfactant as Span during the formulation of formulae. Factors that stabilize the vesicle membrane and increase the entrapment efficiency of KET (namely low HLB, long alkyl chain, high phase transition temperature) slowed down the release profile.

CONCLUSIONS: Proniosomal gels as drug delivery carriers were proven to be a promising approach to increase corneal contact and permeation as well as retention time in the eye resulting in a sustained action and enhanced bioavailability.

Khalil, R. M., G. A. Abdelbary, M. Basha, G. E. A. Awad, and H. A. El-Hashemy, "Design and evaluation of proniosomes as a carrier for ocular delivery of lomefloxacin HCl.", Journal of liposome research, vol. 27, issue 2, pp. 118-129, 2016 May 12, 2017. Abstract

The current investigation aims to develop and evaluate novel ocular proniosomal gels of lomefloxacin HCl (LXN); in order to improve its ocular bioavailability for the management of bacterial conjunctivitis. Proniosomes were prepared using different types of nonionic surfactants solely and as mixtures with Span 60. The formed gels were characterized for entrapment efficiency, vesicle size, and in vitro drug release. Only Span 60 was able to form stable LXN-proniosomal gel when used individually while the other surfactants formed gels only in combination with Span 60 at different ratios. The optimum proniosomal gel; P-LXN 7 (Span 60:Tween 60, 9:1) appeared as spherical shaped vesicles having high entrapment efficiency (>80%), appropriate vesicle size (187 nm) as well as controlled drug release over 12 h. Differential scanning calorimetry confirmed the amorphous nature of LXN within the vesicles. Stability study did not show any significant changes in entrapment efficiency or vesicle size after storage for 3 months at 4 °C. P-LXN 7 was found to be safe and suitable for ocular delivery as proven by the irritancy test. The antibacterial activity of P-LXN 7 evaluated using the susceptibility test and topical therapy of induced ocular conjunctivitis confirmed the enhanced antibacterial therapeutic efficacy of the LXN-proniosomal gel compared to the commercially available LXN eye drops.

Khalil, R. M., G. A. Abdelbary, M. Basha, G. E. A. Awad, and H. A. El-Hashemy, "Enhancement of lomefloxacin Hcl ocular efficacy via niosomal encapsulation: in vitro characterization and in vivo evaluation.", Journal of liposome research, vol. 27, issue 4, pp. 312-323, 2016 Jun 30, 2017. Abstract

The aim of this study is to develop and evaluate niosomal dispersions loaded with the hydrophilic drug; lomefloxacin Hcl (LXN) for the management of ocular bacterial conjunctivitis. LXN-loaded niosomes were prepared by the thin film hydration method following a full factorial formulation design. Two independent variables were evaluated: the type of surfactant (X1) and the surfactant:cholesterol ratio (X2). The dependent variables comprised entrapment efficiency (EE%: Y1), particle size (PS: Y2) and zeta potential (ZP: Y3). The optimum formulation, N-LXN14 (Tw60: CH, 1:1), was spherical in shape and exhibited EE% of 68.41 ± 0.07, PS of 176.0 ± 0.98 and ZP of -40.70 ± 2.20 with a sustained release profile over 8 hours following the Higuchi model. N-LXN14 proved good physicochemical stability under refrigeration up to 3 months. Ocular irritancy test showed no signs of ocular toxicity, confirming the safety and suitability for ocular application. Microbiological evaluation of the antibacterial effect of N-LXN14 was conducted using the susceptibility test and through the induction of topical conjunctivitis by Staphylococcus aureus (S. aureus) followed by topical therapy. Susceptibility test manifested significantly higher percent inhibition of S. aureus and higher AUC0-12 h of N-LXN14 (604.59 ± 0.05) compared to the commercial product (126.25 ± 0.049). Both clinical observation and colony count of the infected eyes after eight days of treatment demonstrated significant improvement in therapeutic response. The infected eyes were completely healed with eradication of S. aureus. In conclusion, the results showed that LXN niosomal dispersions may serve as a promising superior ocular delivery system in the treatment of bacterial conjunctivitis.

Abdelbary, G. A., M. M. Amin, and M. Abdelmoteleb, "Novel mixed hydrotropic solubilization of Zaleplon: Formulation of oral tablets and in-vivo neuropharmacological characterization by monitoring plasma GABA level", Journal of Drug Delivery Science and Technology, vol. 33, pp. 98-113, 2016.
Elsherif, N. I., R. N. Shamma, and G. Abdelbary, "Terbinafine Hydrochloride Trans-ungual Delivery via Nanovesicular Systems: In Vitro Characterization and Ex Vivo Evaluation.", AAPS PharmSciTech, vol. 18, issue 2, pp. 551-562, 2017 Feb. Abstract

Treating a nail infection like onychomycosis is challenging as the human nail plate acts as a formidable barrier against all drug permeation. Available oral and topical treatments have several setbacks. Terbinafine hydrochloride (TBH), belonging to the allylamine class, is mainly used for treatment of onychomycosis. This study aims to formulate TBH in a nanobased spanlastic vesicular carrier that enables and enhances the drug delivery through the nail. The nanovesicles were formulated by ethanol injection method, using either Span® 60 or Span® 65, together with Tween 80 or sodium deoxycholate as an edge activator. A full factorial design was implemented to study the effect of different formulation and process variables on the prepared TBH-loaded spanlastic nanovesicles. TBH entrapment efficiency percentages, particle size diameter, percentage drug released after 2 h and 8 h were selected as dependent variables. Optimization was performed using Design-Expert® software to obtain an optimized formulation with high entrapment efficiency (62.35 ± 8.91%), average particle size of 438.45 ± 70.5 nm, and 29.57 ± 0.93 and 59.53 ± 1.73% TBH released after 2 and 8 h, respectively. The optimized formula was evaluated using differential scanning calorimetry and X-ray diffraction and was also morphologically examined using transmission electron microscopy. An ex vivo study was conducted to determine the permeation and retainment of the optimized formulation in a human cadaver nail plate, and confocal laser scanning microscope was used to show the extent of formulation permeation. In conclusion, the results confirmed that spanlastics exhibit promising results for the trans-ungual delivery of TBH.