Mohamed El-Nabarawi - Academia.edu (original) (raw)

Papers by Mohamed El-Nabarawi

Research Journal of Pharmacy and Technology, 2018

International Journal of Applied Pharmaceutics

A Raft-forming system is an auspicious approach for systematic drug delivery with steady plasma p... more A Raft-forming system is an auspicious approach for systematic drug delivery with steady plasma profiles and drug sustained release manner. It has advantages like enhanced bioavailability, better floating capabilities than other floating systems, more patient compliance, and promoting drug efficacy. Although, it has some problems as it can’t be used for drugs that possess low acid solubility, drugs that are unstable in gastric media, and drugs used for selective release in the colon along with stability difficulties. This system can be successfully prepared by three methods: the physical approach, chemical approach, and physiologically-stimuli approach. The comparative studies showed that the raft-forming system has more advantage over the other comparatives in the antacid potency and in vitro gastric residence time, allowing an intact prolonged delivery of the antacid drug. All the listed applications of the raft system were, fortunately, possessing promising drug delivery with a w...

International Journal of Applied Pharmaceutics

Objective: This study aimed to mask the bitter taste of itopride HCl using the solid dispersion m... more Objective: This study aimed to mask the bitter taste of itopride HCl using the solid dispersion method by solvent evaporation technique and formulate an oral disintegrating tablet (ODT) by direct compression method using different co-processed excipients. Methods: Nine formulae of solid dispersion were prepared to mask the bitter taste of Itopride HCl using Eudragit EPO® and mannitol at different ratios after compatibility studies using infrared spectroscopy (IR). The prepared formulae were subjected to different physicochemical characterization, in vivo taste evaluation, and drug content. The best-selected formulae were used to formulate 10 different ODTs. The prepared tablets were evaluated through hardness, drug content, in vivo-in vitro disintegration, IR, wetting time, and finally, dissolution studies. The selected formula was subjected to a pharmacokinetic study compared to the brand. Results: F5, drug: Eudragit EPO® (1:2) and F8, Drug: Mannitol: Eudragit EPO® (1:1:2) formulae...

Pharmaceutics

Pioglitazone Hydrochloride (PGZ) suffers from poor aqueous solubility. The aim of this research w... more Pioglitazone Hydrochloride (PGZ) suffers from poor aqueous solubility. The aim of this research was to design orally disintegrating tablets with self-nanoemulsifying properties (T-SNEDDS) to improve the Pioglitazone solubility and dissolution rate. Three liquid self-nanoemulsifying systems (L-SNEDDS) were formulated and evaluated for transmittance percentage, emulsification time, particle size, Poly dispersity index (PDI), percentage of content, solubility and stability. The optimum L-SNEDDS formula was converted to a solidified self-nanoemulsifying drug delivery system (S-SNEDDS) by adsorption on Syloid (SYL). Powder characterization tests, such as flowability tests, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM), were performed for the selected S-SNEDDS formulation. Orally disintegrating tablets (ODT) were formulated by blending S-SNEDDS with tableting excipients. The ODT table...

Journal of Nanobiotechnology, 2022

Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens ... more Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles—specifically lipid based nanoparticles—are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, phytosomes, lipid coated nanoparticles, and nanoassemblies. Multiple approaches are used to enhance the tumor uptake as well tumor specificity such as intratumoral injection, passive targeting, active targeting, and stimuli responsive n...

Fluconazole is an imidazole derivative used for the treatment of local and systemic fungal infect... more Fluconazole is an imidazole derivative used for the treatment of local and systemic fungal infection. The oral use of fluconazole is not recommended as it has many side effects. The present study was designed to formulate and evaluate different formulae of topical gel containing fluconazole for treatment of fungal infection of skin. The gel was formulated by using different polymers with different concentration as Carbopol 940, Hydroxypropyl methylcellulose E4M, Methyl cellulose, Pectin and Pluronic P407. Ten different formulae were prepared and characterized physically in term of color, syneresis, spreadability, pH, drug content and rheological properties. Drug-excipients compatibility studies were confirmed by carrying out DSC and FT-IR. In-vitro drug release in phosphate buffer pH 5.5 and permeation study through cellulose membrane, using a modified Franz diffusion cell, were performed. Candida albicans was used as a model fungus to evaluate the antifungal activity of the prepare...

Pharmaceutics, 2021

Acetazolamide (ACZ) is a diuretic used in glaucoma treatment; it has many side effects. Carvedilo... more Acetazolamide (ACZ) is a diuretic used in glaucoma treatment; it has many side effects. Carvedilol (CAR) is a non-cardioselective beta-blocker used in the treatment of elevated intraocular pressure; it is subjected to the first-pass metabolism and causes fluids accumulation leading to edema. This study focuses on overcoming previous side effects by using a topical formula of a combination of the two previous drugs. Sixty formulations of niosomes containing Span 20, Span 60, Tween 20, and Tween 60 with two different ratios were prepared and characterized. Formulation with the lowest particle size (416.30 ± 0.23), the highest zeta potential (72.04 ± 0.43 mv), and the highest apparent coefficient of corneal permeability (0.02 ± 0.29 cm/h) were selected. The selected formula was incorporated into the gel using factorial design 23. Niosomes (acetazolamide/carvedilol) consisting of Span 60 and cholesterol in the molar ratio (7:6), HMPC, and carbopol with two different ratios were used. Th...

Pharmaceutics, 2021

Bisoprolol hemifumarate (BH) is an antihypertensive drug that is used as first-line treatment for... more Bisoprolol hemifumarate (BH) is an antihypertensive drug that is used as first-line treatment for chronic hypertension and angina pectoris. Our study was performed to enhance the transdermal delivery of BH, a hydrophilic drug active with high molecular weight, through differently prepared hydrogels. The synergistic effect of permeation enhancers and iontophoresis was investigated via both ex vivo and in vivo permeation studies. Ex vivo iontophoretic permeation studies were performed by using male albino Wistar rat skin. Cellosolve® hydrogel (F7) showed a 1.5-fold increase in Q180, Jss, and FER compared to F5 (lacking permeation enhancer). BH pharmacokinetic data were studied in human volunteers, following transdermal delivery of F7, using Phoresor® Unit II iontophoresis device, compared to conventional oral tablets. F7 showed 1.9- and 2-fold higher values of Cmax and AUC0–40, respectively compared to Concor® tablets, as well as a smaller Tmax (2.00 ± 2.00 h). The relative bioavailab...

International Journal of Nanomedicine, 2021

Introduction: Hepatitis C virus (HCV) is a significant public health concern that threatens milli... more Introduction: Hepatitis C virus (HCV) is a significant public health concern that threatens millions of individuals worldwide. Daclatasvir (DAC) is a promising direct-acting antiviral approved for treating HCV infection around the world. The goal of this study was to encapsulate DAC into novel polyethylene glycol (PEG) decorated bilosomes (PEG-BILS) to achieve enhanced drug delivery to the liver. Methods: DAC-loaded BILS were primed by a thin film hydrating technique. The study of the impact of various formulation variables on the properties of BILS and selection of the optimal formulation was generated using Design-Expert ® software. The optimum preparation was then pegylated via the incorporation of PEG-6-stearate (5% w/w, with respect to the lipid phase). Results: The optimum PEG-BILS formulation, containing PL:SDC ratio (5:1), 5 mg cholesterol, and 30 min sonication, yielded spherical vesicles in the nanoscale (200±15.2 nm), elevated percent of entrapment efficiency (95.5±7.77%), and a sustained release profile of DAC with 35.11±2.3% release. In vivo and drug distribution studies revealed an enhanced hepatocellular delivery of DAC-loaded PEG-BILS compared to DAC-unPEG-BILS and DAC suspension, where DAC-PEG-BILS achieved 1.19-and 1.54 times the AUC 0-24 of DAC-unPEG-BILS and DAC suspension, respectively. Compared with DAC-unPEG-BILS and DAC suspension, DAC-PEG-BILS delivered about 2 and 3 times higher DAC into the liver, respectively. Conclusion: The innovative encapsulation of DAC-PEG-BILS has a great potential for liver targeting.

ACS Omega, 2020

The aim of this work was to study the influence of process variables on the quality attributes of... more The aim of this work was to study the influence of process variables on the quality attributes of pomegranate extract loaded solid lipid nanoparticles (PE-SLNs) using Plackett− Burman design. PE-SLN formulations were prepared by hot homogenization followed by ultra-sonication technique and evaluated based on the dependent variables that were analyzed utilizing Statgraphics Centurion XV software. The lipid and surfactant (type and concentration), co-surfactant concentration, sonication time, and amplitude were selected as the independent variables (X 1 −X 7). The dependent parameters were particle size, polydispersity index, zeta potential, entrapment efficiency, and cumulative drug release (Y 1 −Y 5). Response surface plots, Pareto charts, and mathematical equations were generated to study the influence of independent variables on the dependent quality parameters. Out of seven variables, X 1 , X 2 , and X 6 have the main significant (p value < 0.05) effect on the entrapment efficiency, the cumulative drug release, the polydispersity index, respectively, while particle size was mainly affected by X 3 , X 6 and zeta potential by X 1 , X 3 , and X 4. Consequently, this screening study revealed that stearic acid as lipid, Tween 80 as surfactant, as well as sonication with short time and high amplitude can be selected for the development of PE-SLN formulation with minimum particle size, maximum zeta potential, highest entrapment, and sustained drug release behavior. Meanwhile, concentrations of lipid, surfactant, and co-surfactant are planned to be scaled up for further optimization study. In conclusion, the Plackett−Burman design verified its influence and significance in determining and understanding both process and formulation variables affecting the quality of PE-SLNs.

Drug Design, Development and Therapy, 2020

This study aimed to prepare solid self-nanoemulsified drug delivery system (S-SNEDDS) of lamotrig... more This study aimed to prepare solid self-nanoemulsified drug delivery system (S-SNEDDS) of lamotrigine (LMG) for enhancing its dissolution and oral bioavailability (BA). Methods: Nineteen liquid SNEDDS were prepared (R1-R19) using D-optimal design with different ratios of oil, surfactant (S), and cosurfactant (Cos). The formulations were characterized regarding robustness to dilution, droplet size, thermodynamic stability testing, selfemulsification time, in-vitro release in 0.1 N HCl and phosphate buffer (PB; pH 6.8). Design Expert ® 11 software was used to select the optimum formulations. Eight S-SNEDDS were prepared (S1-S8) using 2 3 factorial design, and characterized by differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), and scanning electron microscopy (SEM). The optimum formulation was chosen regarding in-vitro drug released in 0.1 N HCl and PB, compared to pure LMG and commercial tablet (Lamictal ®). The BA of LMG from the optimized S-SNEDDS formulation was evaluated in rabbits compared to pure LMG and Lamictal ®. Results: The optimized S-SNEDDS was S2, consisting of R9 adsorbed on Aeroperl ® 300 in a ratio of 1:1, with the best results regarding in-vitro drug released in 0.1 N HCl at 15 min (100%) compared to pure LMG (73.40%) and Lamictal ® (79.43%), and in-vitro drug released in PB at 45 min (100%) compared to pure LMG (30.46%) and Lamictal ® (92.08%). DSC, PXRD, and SEM indicated that LMG was molecularly dispersed within the solid nano-system. The BA of S2 was increased 2.03 and 1.605 folds compared to pure LMG, and Lamictal ® , respectively. Conclusion: S2 is a promising S-SNEDDS formulation. It can be a potential carrier for improving dissolution, and BA of LMG.

Drug Development and Industrial Pharmacy, 2020

Ondansetron HCl is a (5-HT3) serotonin receptor antagonist, used as anti-emetic drug in combinati... more Ondansetron HCl is a (5-HT3) serotonin receptor antagonist, used as anti-emetic drug in combination with anticancer agents. Conventional dosage forms have poor bioavailability and patient compliance. These problems can be reduced by the use of nasal niosomal thermo-reversible in situ gelling system. Niosomes were formulated using various surfactants (Span 60, Span 80, Tween 20, and Tween 80) in different ratios using the thin-film hydration technique. Niosomes were evaluated for particle size, zeta potential, transmission electron microscopy (TEM) imaging, drug entrapment efficiency, and in vitro drug release. Niosomes prepared using Span 60 and cholesterol in the ratio 1:1 (F5) showed higher entrapment efficiency (76.13 ± 1.2%) and in vitro drug release (91.76%) after 12 h was optimized. The optimized niosomes were developed into thermo-reversible in situ gel, composed of Poloxamer 407 and sodium carboxymethyl cellulose, prepared by cold method technique. Compatibility study (FTIR, DSC) was made for drugs and excipients that showed no significant interaction. The gel formulation G5 showed the most suitable gelation temperature (31 C), viscosity (1250 mpoise), bioadhesion force (5860 ± 28 dyne/cm 2), and in vitro drug release (70.6%) after 12 h. Comparative in vivo pharmacokinetic study on rabbits showed a sustained release and higher relative bioavailability of the prepared nasal in situ gel compared to similar dose of oral tablets (202.4%) which make ondansetron HCl niosomal nasal thermo-sensitive in situ gel a more convenient dosage form for the administration of ondansetron HCl than oral tablets.

International Journal of Nanomedicine, 2019

Introduction and aim: Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioava... more Introduction and aim: Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability due to extensive first-pass metabolism. This study aimed to prepare transetho somes (TEs) for enhancing the transdermal delivery of OLM to avoid its oral problems. Methods: TE formulae were prepared utilizing 5 1 .3 1 full factorial design using various surfactants (SAAs) and different phospholipid-to-SAA ratios. The formulae were characterized regarding their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and the amount of drug released after 6 hours (Q6h). Design Expert ® software was employed to select the optimum formula. Results: The optimum formula (TE14) had an EE% of 58.50%±1.30%, PS of 222.60±2.50 nm, PDI of 0.11±0.06, ZP of-20.80±0.30 mV, and Q6h of 67.40%±0.20%. In addition, TE14 was compared to transferosomes (TFs) in terms of elasticity and was found to show higher deformability index. Further, evaluation of ex vivo permeation using both rat and shed snake skin showed higher permeability of TE14 compared to TFs and OLM suspension. Confocal laser scanning microscopy confirmed the capability of the fluoro-labeled TE14 to penetrate deep within the skin, while the histopathological study confirmed its safety. TE14 successfully maintained normal blood pressure values of rats up to 24 hours. Moreover, TE14 showed superiority in dermatokinetic study when compared with drug suspension. Conclusion: Taken together, the obtained results confirmed the potential of employing TEs as a successful carrier for the transdermal delivery of OLM.

Drug Delivery, 2017

The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive ... more The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive gels and lyophilized inserts for intranasal administration to improve GH bioavailability and brain targeting. Carpapol 934 and HPMC were incorporated in GH spanlastic in nasal gels (GHSpNGs). Gelatin and HPMC as matrix former, glycine as a collapse protecting and mannitol as an insert filler and sweeting agent were used to prepare GH spanlastic loaded in lyophilized inserts (GHSpNIs). The prepared GHSpNGs were characterized for pH measurement, drug content, rheology, and in vitro drug release. The prepared GHSpNIs were characterized for drug content, surface pH, GH release, and mucoadhesion. Biological investigations including pharmacokinetics studies and brain drug targeting efficiency dimensions were performed on rats (LC-MS/MS). The results showed thixotropic pseudoplastic gels and white insert with pH values in a physiological range, drug content (89.9-98.6%), (82.4-98.38%) for gel and insert, respectively and rapid release rate of GH. Biological studies showed that C max and AUC 0-6 h in brain and plasma after intranasal administration of gel and insert were higher compared to IV administration of GH solution. A high brain targeting efficiency (199.3%, 230%) for gel and insert, respectively and a direct nose to brain transport (49.8%, 56.95%) for gel and insert, respectively confirmed that there is a direct nose to brain transport of GH following nasal administration of GH spanlastic loaded in nasal gel and insert. GHSpNIs can be considered as potential novel drug delivery system intended for brain targeting via the nasal rout of administration than GHSpNGs.

International Journal of Nanomedicine, 2018

Background: Pomegranate extract (PE) is a natural product with potent antioxidant and anticancer ... more Background: Pomegranate extract (PE) is a natural product with potent antioxidant and anticancer activity because of its polyphenols content. The main purpose of this study was to maximize the PE chemotherapeutic efficacy by loading it in an optimized solid lipid nanoparticles (SLNs) formula. Materials and methods: The influence of independent variables, which were lipid concentration (X 1), surfactant concentration (X 2) and cosurfactant concentration (X 3), on dependent ones, which were particle size (Y 1), polydispersity index (Y 2), zeta potential (Y 3), entrapment efficiency (Y 4) and cumulative % drug release (Y 5), were studied and optimized using the Box-Behnken design. Fifteen formulations of PE-SLNs were prepared using hot homogenization followed by ultra-sonication technique. Response surface plots, Pareto charts and mathematical equations were produced to study the impact of independent variables on the dependent quality parameters. The anti-proliferative activity of the optimized formula was then evaluated in three different cancer cell lines, namely, MCF-7, PC-3 and HepG-2, in addition to one normal cell line, HFB-4. Results: The results demonstrated that the particle sizes ranged from 407.5 to 651.9 nm and the entrapment efficiencies ranged from 56.02 to 65.23%. Interestingly, the 50% inhibitory concentration of the optimized formula had more than a 40-fold improved effect on the cell growth inhibition in comparison with its free counterpart. Furthermore, it was more selective against cancer cells than normal cells particularly in MCF-7 breast cancer cells. Conclusion: These data proved that nanoencapsulation of PE enhanced its anticancer efficacy. Therefore, our results suggested that a PE-loaded SLNs optimized-formula could be a promising chemo therapeutic agent.

Drug development and industrial pharmacy, 2018

Cellulite is a common topographical alteration where skin acquires an orange peel or mattress app... more Cellulite is a common topographical alteration where skin acquires an orange peel or mattress appearance with alterations in adipose tissue and microcirculation. This work aims to develop and evaluate a topical niosomal gel formulae with good permeation to reach the subcutaneous fat layer. Several caffeine niosomal dispersions were prepared and incorporated into gel formulae using Carbopol 940 polymer, chemical penetration enhancers, and iontophoresis, then the prepared gels were applied onto the skin of rats and anticellulite activity of caffeine from the prepared gels compared to that of the commercial product Cellu Destockwas evaluated by histological study of the skin and measurement of plasma level of caffeine passing through the skin using liquid chromatography (LC/MS-MS). Results of histology revealed reduction of size and thickness of fatty layer of rat skin in the following order: FVII > FXIV > Cellu Destock > FVII + Iontophoresis > FXIV + Iontophoresis. Pharmac...

Drug design, development and therapy, 2016

Betahistine dihydrochloride (BH.2HCl), an anti-vertigo histamine analog used in the treatment of ... more Betahistine dihydrochloride (BH.2HCl), an anti-vertigo histamine analog used in the treatment of Ménière's disease, undergoes extensive first-pass metabolism and suffers from short biological half-life. The aim of the present work was to develop and estimate controlled release mucoadhesive buccal tablets of BH.2HCl with a unidirectional drug flow to overcome this encumbrance. A direct compression method was adopted for preparation of the tablets using mucoadhesive polymers like guar gum, hydroxypropyl methyl cellulose K4M, sodium carboxymethyl cellulose and their combinations. The tablets were coated from all surfaces except one surface with a solution of 5% (w/v) cellulose acetate and 1% (w/v) dibutyl phthalate. Different permeation enhancers like 2% sodium deoxycholate, 2% sodium cholate hydrate (SCH) and 5% menthol were tested. Swelling index, ex vivo residence time, mucoadhesion strength, in vivo testing of mucoadhesion time, in vitro dissolution and ex vivo permeation were ...

This study was to investigate the efficiency of buccal dosage forms to deliver poor orally absorb... more This study was to investigate the efficiency of buccal dosage forms to deliver poor orally absorbed drugs. Two buccal gel formulations containing two gastrokinetic drugs with low oral bioavailability; domperidone and mosapride citrate; were tested against their market products. Twenty-four volunteers were enrolled in this study divided into two groups in a single dose, two treatment and two periods cross over design. Both buccal formulations achieved high relative bioavailabilities (Frel) compared to the market products where buccal gel of domperidone achieved Frel of 202% and buccal gel of mosapride citrate achieved 162%. The study reveals the importance of the buccal route for administration of poorly absorbed drugs from the gastrointestinal tract.

International Journal of Pharmaceutics, 2015

Pravastatin sodium (PVS) is a hydrophilic HMG-CoA reductase inhibitor that is mainly absorbed fro... more Pravastatin sodium (PVS) is a hydrophilic HMG-CoA reductase inhibitor that is mainly absorbed from duodenum. PVS has a short elimination half-life (1-3h), suffers from instability at gastric pH, extensive hepatic first-pass metabolism and low absolute bioavailability (18%). The current work aimed to develop enteric surface-coated spanlastic dispersions as controlled-release duodenum-triggered systems able to surmount PVS drawbacks. PVS-loaded spanlastic dispersions were prepared by ethanol-injection method using span(®) 60. Tween(®) 60 and Tween(®) 80 were explored as edge activators. As a novel approach, the fine spanlastic dispersions were surface-coated with an enteric-polymer (Eudragit(®) L100-55) via freeze-drying. The systems were evaluated, before and after enteric-coating, for particle size, zeta potential, PVS entrapment efficiency (EE%), morphology and PVS release studies. PVS pharmacokinetics from the best achieved system and an aqueous solution were estimated in rats by UPLC-MS/MS. The best achieved enteric surface-coated spanlastic dispersion (E-S6) displayed spherical nanosized vesicles (647.60nm) possessing negative zeta potential (-6.93mV), promising EE% (63.22%) and a biphasic drug-release pattern characterized by a retarded-release phase (0.1N HCl, 2h) and a controlled-release phase (pH 6.8, 10h). The higher Cmax, delayed Tmax, prolonged MRT(0-∞), longer elimination t50% and enhanced oral bioavailability unravel E-S6 potential for oral PVS delivery.

Research Journal of Pharmacy and Technology, 2018

International Journal of Applied Pharmaceutics

A Raft-forming system is an auspicious approach for systematic drug delivery with steady plasma p... more A Raft-forming system is an auspicious approach for systematic drug delivery with steady plasma profiles and drug sustained release manner. It has advantages like enhanced bioavailability, better floating capabilities than other floating systems, more patient compliance, and promoting drug efficacy. Although, it has some problems as it can’t be used for drugs that possess low acid solubility, drugs that are unstable in gastric media, and drugs used for selective release in the colon along with stability difficulties. This system can be successfully prepared by three methods: the physical approach, chemical approach, and physiologically-stimuli approach. The comparative studies showed that the raft-forming system has more advantage over the other comparatives in the antacid potency and in vitro gastric residence time, allowing an intact prolonged delivery of the antacid drug. All the listed applications of the raft system were, fortunately, possessing promising drug delivery with a w...

International Journal of Applied Pharmaceutics

Objective: This study aimed to mask the bitter taste of itopride HCl using the solid dispersion m... more Objective: This study aimed to mask the bitter taste of itopride HCl using the solid dispersion method by solvent evaporation technique and formulate an oral disintegrating tablet (ODT) by direct compression method using different co-processed excipients. Methods: Nine formulae of solid dispersion were prepared to mask the bitter taste of Itopride HCl using Eudragit EPO® and mannitol at different ratios after compatibility studies using infrared spectroscopy (IR). The prepared formulae were subjected to different physicochemical characterization, in vivo taste evaluation, and drug content. The best-selected formulae were used to formulate 10 different ODTs. The prepared tablets were evaluated through hardness, drug content, in vivo-in vitro disintegration, IR, wetting time, and finally, dissolution studies. The selected formula was subjected to a pharmacokinetic study compared to the brand. Results: F5, drug: Eudragit EPO® (1:2) and F8, Drug: Mannitol: Eudragit EPO® (1:1:2) formulae...

Pharmaceutics

Pioglitazone Hydrochloride (PGZ) suffers from poor aqueous solubility. The aim of this research w... more Pioglitazone Hydrochloride (PGZ) suffers from poor aqueous solubility. The aim of this research was to design orally disintegrating tablets with self-nanoemulsifying properties (T-SNEDDS) to improve the Pioglitazone solubility and dissolution rate. Three liquid self-nanoemulsifying systems (L-SNEDDS) were formulated and evaluated for transmittance percentage, emulsification time, particle size, Poly dispersity index (PDI), percentage of content, solubility and stability. The optimum L-SNEDDS formula was converted to a solidified self-nanoemulsifying drug delivery system (S-SNEDDS) by adsorption on Syloid (SYL). Powder characterization tests, such as flowability tests, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM), were performed for the selected S-SNEDDS formulation. Orally disintegrating tablets (ODT) were formulated by blending S-SNEDDS with tableting excipients. The ODT table...

Journal of Nanobiotechnology, 2022

Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens ... more Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles—specifically lipid based nanoparticles—are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, phytosomes, lipid coated nanoparticles, and nanoassemblies. Multiple approaches are used to enhance the tumor uptake as well tumor specificity such as intratumoral injection, passive targeting, active targeting, and stimuli responsive n...

Fluconazole is an imidazole derivative used for the treatment of local and systemic fungal infect... more Fluconazole is an imidazole derivative used for the treatment of local and systemic fungal infection. The oral use of fluconazole is not recommended as it has many side effects. The present study was designed to formulate and evaluate different formulae of topical gel containing fluconazole for treatment of fungal infection of skin. The gel was formulated by using different polymers with different concentration as Carbopol 940, Hydroxypropyl methylcellulose E4M, Methyl cellulose, Pectin and Pluronic P407. Ten different formulae were prepared and characterized physically in term of color, syneresis, spreadability, pH, drug content and rheological properties. Drug-excipients compatibility studies were confirmed by carrying out DSC and FT-IR. In-vitro drug release in phosphate buffer pH 5.5 and permeation study through cellulose membrane, using a modified Franz diffusion cell, were performed. Candida albicans was used as a model fungus to evaluate the antifungal activity of the prepare...

Pharmaceutics, 2021

Acetazolamide (ACZ) is a diuretic used in glaucoma treatment; it has many side effects. Carvedilo... more Acetazolamide (ACZ) is a diuretic used in glaucoma treatment; it has many side effects. Carvedilol (CAR) is a non-cardioselective beta-blocker used in the treatment of elevated intraocular pressure; it is subjected to the first-pass metabolism and causes fluids accumulation leading to edema. This study focuses on overcoming previous side effects by using a topical formula of a combination of the two previous drugs. Sixty formulations of niosomes containing Span 20, Span 60, Tween 20, and Tween 60 with two different ratios were prepared and characterized. Formulation with the lowest particle size (416.30 ± 0.23), the highest zeta potential (72.04 ± 0.43 mv), and the highest apparent coefficient of corneal permeability (0.02 ± 0.29 cm/h) were selected. The selected formula was incorporated into the gel using factorial design 23. Niosomes (acetazolamide/carvedilol) consisting of Span 60 and cholesterol in the molar ratio (7:6), HMPC, and carbopol with two different ratios were used. Th...

Pharmaceutics, 2021

Bisoprolol hemifumarate (BH) is an antihypertensive drug that is used as first-line treatment for... more Bisoprolol hemifumarate (BH) is an antihypertensive drug that is used as first-line treatment for chronic hypertension and angina pectoris. Our study was performed to enhance the transdermal delivery of BH, a hydrophilic drug active with high molecular weight, through differently prepared hydrogels. The synergistic effect of permeation enhancers and iontophoresis was investigated via both ex vivo and in vivo permeation studies. Ex vivo iontophoretic permeation studies were performed by using male albino Wistar rat skin. Cellosolve® hydrogel (F7) showed a 1.5-fold increase in Q180, Jss, and FER compared to F5 (lacking permeation enhancer). BH pharmacokinetic data were studied in human volunteers, following transdermal delivery of F7, using Phoresor® Unit II iontophoresis device, compared to conventional oral tablets. F7 showed 1.9- and 2-fold higher values of Cmax and AUC0–40, respectively compared to Concor® tablets, as well as a smaller Tmax (2.00 ± 2.00 h). The relative bioavailab...

International Journal of Nanomedicine, 2021

Introduction: Hepatitis C virus (HCV) is a significant public health concern that threatens milli... more Introduction: Hepatitis C virus (HCV) is a significant public health concern that threatens millions of individuals worldwide. Daclatasvir (DAC) is a promising direct-acting antiviral approved for treating HCV infection around the world. The goal of this study was to encapsulate DAC into novel polyethylene glycol (PEG) decorated bilosomes (PEG-BILS) to achieve enhanced drug delivery to the liver. Methods: DAC-loaded BILS were primed by a thin film hydrating technique. The study of the impact of various formulation variables on the properties of BILS and selection of the optimal formulation was generated using Design-Expert ® software. The optimum preparation was then pegylated via the incorporation of PEG-6-stearate (5% w/w, with respect to the lipid phase). Results: The optimum PEG-BILS formulation, containing PL:SDC ratio (5:1), 5 mg cholesterol, and 30 min sonication, yielded spherical vesicles in the nanoscale (200±15.2 nm), elevated percent of entrapment efficiency (95.5±7.77%), and a sustained release profile of DAC with 35.11±2.3% release. In vivo and drug distribution studies revealed an enhanced hepatocellular delivery of DAC-loaded PEG-BILS compared to DAC-unPEG-BILS and DAC suspension, where DAC-PEG-BILS achieved 1.19-and 1.54 times the AUC 0-24 of DAC-unPEG-BILS and DAC suspension, respectively. Compared with DAC-unPEG-BILS and DAC suspension, DAC-PEG-BILS delivered about 2 and 3 times higher DAC into the liver, respectively. Conclusion: The innovative encapsulation of DAC-PEG-BILS has a great potential for liver targeting.

ACS Omega, 2020

The aim of this work was to study the influence of process variables on the quality attributes of... more The aim of this work was to study the influence of process variables on the quality attributes of pomegranate extract loaded solid lipid nanoparticles (PE-SLNs) using Plackett− Burman design. PE-SLN formulations were prepared by hot homogenization followed by ultra-sonication technique and evaluated based on the dependent variables that were analyzed utilizing Statgraphics Centurion XV software. The lipid and surfactant (type and concentration), co-surfactant concentration, sonication time, and amplitude were selected as the independent variables (X 1 −X 7). The dependent parameters were particle size, polydispersity index, zeta potential, entrapment efficiency, and cumulative drug release (Y 1 −Y 5). Response surface plots, Pareto charts, and mathematical equations were generated to study the influence of independent variables on the dependent quality parameters. Out of seven variables, X 1 , X 2 , and X 6 have the main significant (p value < 0.05) effect on the entrapment efficiency, the cumulative drug release, the polydispersity index, respectively, while particle size was mainly affected by X 3 , X 6 and zeta potential by X 1 , X 3 , and X 4. Consequently, this screening study revealed that stearic acid as lipid, Tween 80 as surfactant, as well as sonication with short time and high amplitude can be selected for the development of PE-SLN formulation with minimum particle size, maximum zeta potential, highest entrapment, and sustained drug release behavior. Meanwhile, concentrations of lipid, surfactant, and co-surfactant are planned to be scaled up for further optimization study. In conclusion, the Plackett−Burman design verified its influence and significance in determining and understanding both process and formulation variables affecting the quality of PE-SLNs.

Drug Design, Development and Therapy, 2020

This study aimed to prepare solid self-nanoemulsified drug delivery system (S-SNEDDS) of lamotrig... more This study aimed to prepare solid self-nanoemulsified drug delivery system (S-SNEDDS) of lamotrigine (LMG) for enhancing its dissolution and oral bioavailability (BA). Methods: Nineteen liquid SNEDDS were prepared (R1-R19) using D-optimal design with different ratios of oil, surfactant (S), and cosurfactant (Cos). The formulations were characterized regarding robustness to dilution, droplet size, thermodynamic stability testing, selfemulsification time, in-vitro release in 0.1 N HCl and phosphate buffer (PB; pH 6.8). Design Expert ® 11 software was used to select the optimum formulations. Eight S-SNEDDS were prepared (S1-S8) using 2 3 factorial design, and characterized by differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), and scanning electron microscopy (SEM). The optimum formulation was chosen regarding in-vitro drug released in 0.1 N HCl and PB, compared to pure LMG and commercial tablet (Lamictal ®). The BA of LMG from the optimized S-SNEDDS formulation was evaluated in rabbits compared to pure LMG and Lamictal ®. Results: The optimized S-SNEDDS was S2, consisting of R9 adsorbed on Aeroperl ® 300 in a ratio of 1:1, with the best results regarding in-vitro drug released in 0.1 N HCl at 15 min (100%) compared to pure LMG (73.40%) and Lamictal ® (79.43%), and in-vitro drug released in PB at 45 min (100%) compared to pure LMG (30.46%) and Lamictal ® (92.08%). DSC, PXRD, and SEM indicated that LMG was molecularly dispersed within the solid nano-system. The BA of S2 was increased 2.03 and 1.605 folds compared to pure LMG, and Lamictal ® , respectively. Conclusion: S2 is a promising S-SNEDDS formulation. It can be a potential carrier for improving dissolution, and BA of LMG.

Drug Development and Industrial Pharmacy, 2020

Ondansetron HCl is a (5-HT3) serotonin receptor antagonist, used as anti-emetic drug in combinati... more Ondansetron HCl is a (5-HT3) serotonin receptor antagonist, used as anti-emetic drug in combination with anticancer agents. Conventional dosage forms have poor bioavailability and patient compliance. These problems can be reduced by the use of nasal niosomal thermo-reversible in situ gelling system. Niosomes were formulated using various surfactants (Span 60, Span 80, Tween 20, and Tween 80) in different ratios using the thin-film hydration technique. Niosomes were evaluated for particle size, zeta potential, transmission electron microscopy (TEM) imaging, drug entrapment efficiency, and in vitro drug release. Niosomes prepared using Span 60 and cholesterol in the ratio 1:1 (F5) showed higher entrapment efficiency (76.13 ± 1.2%) and in vitro drug release (91.76%) after 12 h was optimized. The optimized niosomes were developed into thermo-reversible in situ gel, composed of Poloxamer 407 and sodium carboxymethyl cellulose, prepared by cold method technique. Compatibility study (FTIR, DSC) was made for drugs and excipients that showed no significant interaction. The gel formulation G5 showed the most suitable gelation temperature (31 C), viscosity (1250 mpoise), bioadhesion force (5860 ± 28 dyne/cm 2), and in vitro drug release (70.6%) after 12 h. Comparative in vivo pharmacokinetic study on rabbits showed a sustained release and higher relative bioavailability of the prepared nasal in situ gel compared to similar dose of oral tablets (202.4%) which make ondansetron HCl niosomal nasal thermo-sensitive in situ gel a more convenient dosage form for the administration of ondansetron HCl than oral tablets.

International Journal of Nanomedicine, 2019

Introduction and aim: Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioava... more Introduction and aim: Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability due to extensive first-pass metabolism. This study aimed to prepare transetho somes (TEs) for enhancing the transdermal delivery of OLM to avoid its oral problems. Methods: TE formulae were prepared utilizing 5 1 .3 1 full factorial design using various surfactants (SAAs) and different phospholipid-to-SAA ratios. The formulae were characterized regarding their entrapment efficiency percentage (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and the amount of drug released after 6 hours (Q6h). Design Expert ® software was employed to select the optimum formula. Results: The optimum formula (TE14) had an EE% of 58.50%±1.30%, PS of 222.60±2.50 nm, PDI of 0.11±0.06, ZP of-20.80±0.30 mV, and Q6h of 67.40%±0.20%. In addition, TE14 was compared to transferosomes (TFs) in terms of elasticity and was found to show higher deformability index. Further, evaluation of ex vivo permeation using both rat and shed snake skin showed higher permeability of TE14 compared to TFs and OLM suspension. Confocal laser scanning microscopy confirmed the capability of the fluoro-labeled TE14 to penetrate deep within the skin, while the histopathological study confirmed its safety. TE14 successfully maintained normal blood pressure values of rats up to 24 hours. Moreover, TE14 showed superiority in dermatokinetic study when compared with drug suspension. Conclusion: Taken together, the obtained results confirmed the potential of employing TEs as a successful carrier for the transdermal delivery of OLM.

Drug Delivery, 2017

The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive ... more The aim of this study was to formulate granisetron hydrochloride (GH) spanlastic in mucoadhesive gels and lyophilized inserts for intranasal administration to improve GH bioavailability and brain targeting. Carpapol 934 and HPMC were incorporated in GH spanlastic in nasal gels (GHSpNGs). Gelatin and HPMC as matrix former, glycine as a collapse protecting and mannitol as an insert filler and sweeting agent were used to prepare GH spanlastic loaded in lyophilized inserts (GHSpNIs). The prepared GHSpNGs were characterized for pH measurement, drug content, rheology, and in vitro drug release. The prepared GHSpNIs were characterized for drug content, surface pH, GH release, and mucoadhesion. Biological investigations including pharmacokinetics studies and brain drug targeting efficiency dimensions were performed on rats (LC-MS/MS). The results showed thixotropic pseudoplastic gels and white insert with pH values in a physiological range, drug content (89.9-98.6%), (82.4-98.38%) for gel and insert, respectively and rapid release rate of GH. Biological studies showed that C max and AUC 0-6 h in brain and plasma after intranasal administration of gel and insert were higher compared to IV administration of GH solution. A high brain targeting efficiency (199.3%, 230%) for gel and insert, respectively and a direct nose to brain transport (49.8%, 56.95%) for gel and insert, respectively confirmed that there is a direct nose to brain transport of GH following nasal administration of GH spanlastic loaded in nasal gel and insert. GHSpNIs can be considered as potential novel drug delivery system intended for brain targeting via the nasal rout of administration than GHSpNGs.

International Journal of Nanomedicine, 2018

Background: Pomegranate extract (PE) is a natural product with potent antioxidant and anticancer ... more Background: Pomegranate extract (PE) is a natural product with potent antioxidant and anticancer activity because of its polyphenols content. The main purpose of this study was to maximize the PE chemotherapeutic efficacy by loading it in an optimized solid lipid nanoparticles (SLNs) formula. Materials and methods: The influence of independent variables, which were lipid concentration (X 1), surfactant concentration (X 2) and cosurfactant concentration (X 3), on dependent ones, which were particle size (Y 1), polydispersity index (Y 2), zeta potential (Y 3), entrapment efficiency (Y 4) and cumulative % drug release (Y 5), were studied and optimized using the Box-Behnken design. Fifteen formulations of PE-SLNs were prepared using hot homogenization followed by ultra-sonication technique. Response surface plots, Pareto charts and mathematical equations were produced to study the impact of independent variables on the dependent quality parameters. The anti-proliferative activity of the optimized formula was then evaluated in three different cancer cell lines, namely, MCF-7, PC-3 and HepG-2, in addition to one normal cell line, HFB-4. Results: The results demonstrated that the particle sizes ranged from 407.5 to 651.9 nm and the entrapment efficiencies ranged from 56.02 to 65.23%. Interestingly, the 50% inhibitory concentration of the optimized formula had more than a 40-fold improved effect on the cell growth inhibition in comparison with its free counterpart. Furthermore, it was more selective against cancer cells than normal cells particularly in MCF-7 breast cancer cells. Conclusion: These data proved that nanoencapsulation of PE enhanced its anticancer efficacy. Therefore, our results suggested that a PE-loaded SLNs optimized-formula could be a promising chemo therapeutic agent.

Drug development and industrial pharmacy, 2018

Cellulite is a common topographical alteration where skin acquires an orange peel or mattress app... more Cellulite is a common topographical alteration where skin acquires an orange peel or mattress appearance with alterations in adipose tissue and microcirculation. This work aims to develop and evaluate a topical niosomal gel formulae with good permeation to reach the subcutaneous fat layer. Several caffeine niosomal dispersions were prepared and incorporated into gel formulae using Carbopol 940 polymer, chemical penetration enhancers, and iontophoresis, then the prepared gels were applied onto the skin of rats and anticellulite activity of caffeine from the prepared gels compared to that of the commercial product Cellu Destockwas evaluated by histological study of the skin and measurement of plasma level of caffeine passing through the skin using liquid chromatography (LC/MS-MS). Results of histology revealed reduction of size and thickness of fatty layer of rat skin in the following order: FVII > FXIV > Cellu Destock > FVII + Iontophoresis > FXIV + Iontophoresis. Pharmac...

Drug design, development and therapy, 2016

Betahistine dihydrochloride (BH.2HCl), an anti-vertigo histamine analog used in the treatment of ... more Betahistine dihydrochloride (BH.2HCl), an anti-vertigo histamine analog used in the treatment of Ménière's disease, undergoes extensive first-pass metabolism and suffers from short biological half-life. The aim of the present work was to develop and estimate controlled release mucoadhesive buccal tablets of BH.2HCl with a unidirectional drug flow to overcome this encumbrance. A direct compression method was adopted for preparation of the tablets using mucoadhesive polymers like guar gum, hydroxypropyl methyl cellulose K4M, sodium carboxymethyl cellulose and their combinations. The tablets were coated from all surfaces except one surface with a solution of 5% (w/v) cellulose acetate and 1% (w/v) dibutyl phthalate. Different permeation enhancers like 2% sodium deoxycholate, 2% sodium cholate hydrate (SCH) and 5% menthol were tested. Swelling index, ex vivo residence time, mucoadhesion strength, in vivo testing of mucoadhesion time, in vitro dissolution and ex vivo permeation were ...

This study was to investigate the efficiency of buccal dosage forms to deliver poor orally absorb... more This study was to investigate the efficiency of buccal dosage forms to deliver poor orally absorbed drugs. Two buccal gel formulations containing two gastrokinetic drugs with low oral bioavailability; domperidone and mosapride citrate; were tested against their market products. Twenty-four volunteers were enrolled in this study divided into two groups in a single dose, two treatment and two periods cross over design. Both buccal formulations achieved high relative bioavailabilities (Frel) compared to the market products where buccal gel of domperidone achieved Frel of 202% and buccal gel of mosapride citrate achieved 162%. The study reveals the importance of the buccal route for administration of poorly absorbed drugs from the gastrointestinal tract.

International Journal of Pharmaceutics, 2015

Pravastatin sodium (PVS) is a hydrophilic HMG-CoA reductase inhibitor that is mainly absorbed fro... more Pravastatin sodium (PVS) is a hydrophilic HMG-CoA reductase inhibitor that is mainly absorbed from duodenum. PVS has a short elimination half-life (1-3h), suffers from instability at gastric pH, extensive hepatic first-pass metabolism and low absolute bioavailability (18%). The current work aimed to develop enteric surface-coated spanlastic dispersions as controlled-release duodenum-triggered systems able to surmount PVS drawbacks. PVS-loaded spanlastic dispersions were prepared by ethanol-injection method using span(®) 60. Tween(®) 60 and Tween(®) 80 were explored as edge activators. As a novel approach, the fine spanlastic dispersions were surface-coated with an enteric-polymer (Eudragit(®) L100-55) via freeze-drying. The systems were evaluated, before and after enteric-coating, for particle size, zeta potential, PVS entrapment efficiency (EE%), morphology and PVS release studies. PVS pharmacokinetics from the best achieved system and an aqueous solution were estimated in rats by UPLC-MS/MS. The best achieved enteric surface-coated spanlastic dispersion (E-S6) displayed spherical nanosized vesicles (647.60nm) possessing negative zeta potential (-6.93mV), promising EE% (63.22%) and a biphasic drug-release pattern characterized by a retarded-release phase (0.1N HCl, 2h) and a controlled-release phase (pH 6.8, 10h). The higher Cmax, delayed Tmax, prolonged MRT(0-∞), longer elimination t50% and enhanced oral bioavailability unravel E-S6 potential for oral PVS delivery.