Abdel-Azim Zaghloul - Academia.edu (original) (raw)

Papers by Abdel-Azim Zaghloul

PubMed, Sep 1, 2008

The main purposes of this work were to prepare, characterize and optimize a self-emulsified drug ... more The main purposes of this work were to prepare, characterize and optimize a self-emulsified drug delivery system of probucol (PBSEDDS) with enhanced dissolution and better chance for oral absorption. The methods included determination of the solubility of probucol in different oils, surfactants and co-surfactants using saturation solubility method and HPLC for drug analysis. The ingredients showing high drug solubility were used to prepare PBSEDDS after being tested for physical and chemical compatibility with the drug using DSC and FTIR. The prepared formulations were evaluated for droplet size, turbidity, spontaneity of emulsification and dissolution in water. Optimization was performed using a three-factor, three-level Box-Behnken experimental design. The results showed high drug solubility and compatibility with soybean oil (solvent), Labrafil M1944CS (surfactant) and Capmul MCM-C8 (cosurfactant). Oil to surfactant/co-surfactant ratio showed large influence on the characteristics of PBSEDDS. Several fold improvement of drug dissolution was observed compared to drug solution in soybean oil alone. Optimization study showed that observed and predicted values of cumulative percent drug dissolution after 60 min were in reasonable agreement. The experimental design applied helped in understanding the effects and the interaction effects between the independent factors. The prepared PBSEDDS may have the potential to enhance the therapeutic bioavailability of probucol.

Medical Principles and Practice, 2011

Medical Principles and Practice, 2011

Access to full text and tables of contents, including tentative ones for forthcoming issues: www.... more Access to full text and tables of contents, including tentative ones for forthcoming issues: www.karger.com/mpp_issues 60 Diagnostic Yield and Clinical Impact of Capsule Endoscopy in Obscure Gastrointestinal Bleeding during Routine Clinical

Acta Pharmaceutica, 2014

Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobic... more Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobicity and large molecular mass. The aim of the present study was to develop alpha-tocopherol (T) topical formulations and evaluate their ex vivo and in vivo permeation. Franz diffusion cells were used for ex vivo permeation, and neonatal rats were used for in vivo permeation. Seven gel formulations and 21 liquid formulations were investigated for physical stability, viscosity and permeation of T. Analysis of T was performed by a validated HPLC method using a UV detector. The ex vivo permeation from gel and emulsion formulations was very poor (0.001-0.015 %). Highest permeation was observed from monophasic liquid formulations containing dimethyl sulfoxide (DMSO), tocopheryl polyethylene glycols (TPGs), propylene glycol, ethanol and 9.5 % T. The in vivo results demonstrated higher retention in the epidermis compared to subcutaneous tissues, 1377 and 1.13 μg g-1, respectively. Increasing T co...

Ibuprofen (IB) a NSAID, has poor dissolution and many gastrointestinal side effects. Self-Emulsif... more Ibuprofen (IB) a NSAID, has poor dissolution and many gastrointestinal side effects. Self-Emulsifying drug delivery system (SEDDS) has proved its efficacy to improve the solu bility and dissolution of many lipophilic drugs and improve their characteristics. The object ives of this study were to develop, optimize and ch aracterize a IBSEDDS applying Face Centered Experimental Design (FCED). The methods included determination of solubility of IB in different oils, surfactants and co-surfactants. Ingredient showing high drug solub ility were used to formulate several IBSEDDS after being teste d for physical and chemical compatibility with the drug. A three factor, three level FCED was used for the opt imization process. The concentration of oil, surfac tant and cosurfactant were the independent variables, X1, X2 and X3 respectively, while the dissolution, turbid ity and droplet size were the dependent variables, Y1, Y2 a nd Y3 respectively. The results showed high solubil ity and compa...

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.

International Journal of Pharmaceutics, 2002

The objectives of the present study were (1) to evaluate the effect of formulation ingredients on... more The objectives of the present study were (1) to evaluate the effect of formulation ingredients on the release rate of Ubiquinone from its adsorbing solid compact; and (2) to prepare and evaluate an optimized self-nanoemulsified tablet formulation. A three factor, three-level Box-Behnken design was used for the optimization procedure, with the amounts of copolyvidone (X 1), maltodextrin (X 2) and microcrystalline cellulose (X 3) as the independent variables. The response variable was cumulative percent of Ubiquinone emulsified in 45 min with constraints on weight, flowability index, tensile strength, friability and disintegration time of the dry powdered emulsion and the resultant compact. Based on the experimental design, different Ubiquinone release rates and profiles were obtained. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the cumulative percent emulsified in 45 min was Y 6 = 64.10− 12.32X 1 − 4.36X 2 − 25.53X 3 + 6.99X 1 X 2 +3.97X 1 X 3 + 9.70X 2 X 3 −8.98X 1 2 −16.22X 2 2 + 17.10X 3 2. The optimization model predicted an 85.4% release with X 1 , X 2 and X 3 levels of 66.6, 560.1 and 100, respectively. A new formulation was prepared according to these levels. The observed responses were in close agreement with the predicted values of the optimized formulation.

Pharmazie

The main purposes of this work were to prepare, characterize and optimize a self-emulsified drug ... more The main purposes of this work were to prepare, characterize and optimize a self-emulsified drug delivery system of probucol (PBSEDDS) with enhanced dissolution and better chance for oral absorption. The methods included determination of the solubility of probucol in different oils, surfactants and co-surfactants using saturation solubility method and HPLC for drug analysis. The ingredients showing high drug solubility were used to prepare PBSEDDS after being tested for physical and chemical compatibility with the drug using DSC and FTIR. The prepared formulations were evaluated for droplet size, turbidity, spontaneity of emulsification and dissolution in water. Optimization was performed using a three-factor, three-level Box-Behnken experimental design. The results showed high drug solubility and compatibility with soybean oil (solvent), Labrafil M1944CS (surfactant) and Capmul MCM-C8 (cosurfactant). Oil to surfactant/co-surfactant ratio showed large influence on the characteristic...

Pharmazie

The purposes of this study were to assess the mucoadhesion and bioavailability and their correlat... more The purposes of this study were to assess the mucoadhesion and bioavailability and their correlation for ketoprofen tablet dosage forms (F1-F6) containing polycarbophil (PC), sodium carboxymethylcellulose (Na CMC) as bioadhesives, Avicel pH 101 as direct compressible tablet vehicle or mixtures of these, and non compressible vehicles such as lactose and starch. For mucoadhesion assessment, we used sheep gastric mucosa and for bioavailability we used six human volunteers in an open randomized seven-way crossover study. Young's modulus (YM) and relative bioavailability (RB) parameters were used for evaluation of mucoadhesion and bioavailability, respectively. The results indicated that F2 containing Na CMC (72.5%) showed the highest value of YM (7.6 +/- 0.76 pascals) and 119.4 +/- 3.2% for RB. Decreasing the amount of Na CMC to 10% in F3 and F6 decreased the values of YM and RB to 1.4 +/- 0.08 and 84 +/- 2.05 in F3, 4.6 +/- 0.43 and 114.7 +/- 2.46 in F6, respectively. The highest R...

Drug discoveries & therapeutics, 2008

The aim of the present study was to use factorial design to enhance the dissolution rate of nimes... more The aim of the present study was to use factorial design to enhance the dissolution rate of nimesulide using solid binary systems with the hydrophilic carriers D-mannitol and polyethylene glycol (PEG 4000). Two-factor full factorial design was employed to investigate the effects of the drug/carrier ratio (X(1), 10 and 20%) and the method of preparation (X(2), physical or co-melted mixture) on the percent drug release after 60 min (Y(1)). Drugcarrier co-melted mixtures were prepared by melting the carriers D-mannitol or PEG with the drug. For physical mixtures, the drug and carrier were mixed thoroughly in a mortar until a homogeneous mixture was obtained. Drug-carrier interactions were investigated by differential scanning calorimetry (DSC). All prepared mixtures were filled in hard gelatin capsules, size 0, and then their dissolution rate was tested. The results showed an increase in the solubility of the drug with increasing polymer concentrations. Thermal analysis revealed no not...

Die Pharmazie, 2001

Old and recent reports show that honey has beneficial effects on the skin as antiseptic for wound... more Old and recent reports show that honey has beneficial effects on the skin as antiseptic for wounds, burns and ulcers and as a healing promoter. Many investigators confirmed the usefulness of honey in the treatment of skin infections as well as internal diseases. The factors behind these effects are not completely explained. The aim of this study is: a) to investigate the antimicrobial activity of crude honey, b) to separate the fractions responsible for its activity, c) to formulate the honey extract as semisolid dosage forms, d) to study its release, and e) to determine its stability. The results showed that the ethylacetate honey extract showed antibacterial, anticandida and antifungal effects at low concentration. The release of honey extract from different ointment bases was depending on the constituents of the base, and its stability was found to be temperature and base dependent.

Die Pharmazie, 2001

A novel method was developed for the quantitative determination of ubidecarenone (CoQ10) in aqueo... more A novel method was developed for the quantitative determination of ubidecarenone (CoQ10) in aqueous media using non aqueous reversed phase liquid chromatography. Standards were prepared by melting the compound in Cremophor EL followed by dilution with distilled water. Samples were then analyzed by a Reverse Phase HPLC method using a Waters Novapak C18, 3.9 x 150 mm column. The mobile phase used was methanol: n-hexane (9:1) at a flow rate of 1.5 ml/min. Response of the detector to the analyte was linear (r: 0.999) over the range of 2.5-100 micrograms ml-1, with a limit of detection of 0.17 microgram ml-1. Acetone used to solubilize CoQ10 in the surfactant and Cremophor EL did not interfere with sample analysis. This method provided a convenient and alternative approach to the existing methods that require organic solvent extractions prior to analysis. Besides, this method enabled the separation of major photolytic decomposition products of CoQ10.

Die Pharmazie, 2001

The objectives of the present study were to screen the formulation and process variables for the ... more The objectives of the present study were to screen the formulation and process variables for the preparation of extended release naproxen tablets with Eudragit L100-55. The tablets were prepared by compression of microspheres that were obtained by a coprecipitation technique. The process involved dissolution of naproxen and Eudragit L 100-55 in alcohol USP followed by the addition of an aqueous solution containing a surfactant and deaggregating agents. The mixture was stirred for a specified time period to obtain microspheres, which were filtered and air-dried to a constant weight. The microspheres were then compressed to obtain plain tablets with a diameter of 12 mm. A 7-factor 12-run Plackett-Burman screening design was employed to evaluate the main effects of homogenization time (X1), rate of water addition (X2), amount of polymer (X3), amount of precipitating solution (X4), concentration of electrolytes (X5), compression pressure (X6), and the concentration of lubricant (X7) on ...

The authors evaluate the effect of microcrystalline cellulose (MCC) on the tableting performance,... more The authors evaluate the effect of microcrystalline cellulose (MCC) on the tableting performance, surface roughness, and dissolution properties of a dry adsorbed self-nanoemulsified powdered formulation. Heckel analysis was used to study the tabletability, compressibility, and compactibility of six formulas prepared with various MCC grades. Surface topography revealed a higher degree of waviness at the lower surface of the compacts as the result of granule segregation. The dissolution rate of the nanoemulsion from the tablets increased with increasing MCC particle size. Good flow properties of the formulations resulted from the granular nature of the mixtures. Low hardness and friability indicated oil-induced bridging between the particles.

Pharmaceutical Development and Technology, 2006

The purpose of this work was to evaluate the main and interaction effects of formulation factors ... more The purpose of this work was to evaluate the main and interaction effects of formulation factors on the drug encapsulation efficiency of beta-estradiol biodegradable microspheres by applying response surface methodology. A secondary purpose was to obtain an optimized formula for long-term therapy of osteoporosis. A three factor, three level Box-Behnken experimental design was used to get 15 experimental runs. The independent variables were drug/polymer ratio (X1), dispersing agent concentration (X2), and deaggregating agent concentration (X3). The dependent variables were percentage encapsulation efficiency (Y1), cumulative percent drug released (Y2), and percentage yield of the microspheres (Y3). The formulations were prepared by emulsion solvent evaporation technique using ethyl acetate as organic solvent. The optimized formulation was maximized for encapsulation efficiency and further characterized for the particle size distribution, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR). The mathematical relationship obtained between X1, X2, X3, and Y1 was: Y1 = -129.85 + 29.35X1 + 129.99X2 + 64.82X3 - 3.2X1X2 - 0.29X1X3 - 35.83X2X3 - 2.05X(2)(1) - 13.23X(2)(2) - 5.92X(2)(3) (R2 = 0.99) The equation showed that X1, X2, and X3 affect Y1 positively but interaction between any two of these factors affects Y1 negatively. The most significant interaction was between X2 and X3. The finding indicated that controlled releases beta-estradiol biodegradable microspheres with high encapsulation efficiency and low pulsatile release can be prepared and the quantitative response surface methodology applied helped in understanding the effects and the interaction effects between the three factors applied.

Journal of Pharmaceutical and Biomedical Analysis, 2003

An isocratic reversed phase high-performance liquid chromatographic (HPLC) method with ultraviole... more An isocratic reversed phase high-performance liquid chromatographic (HPLC) method with ultraviolet detection at 205 nm has been developed for the determination of cyclosporin-A (CyA) in rat blood and plasma. Naproxen was successfully used as an internal standard. Blood or plasma samples were pretreated by liquid–liquid extraction with diethyl ether. The ether extract was evaporated and the residue was reconstituted in

Current Drug Delivery, 2018

Background: Self-Emulsifying Drug Delivery System (SEDDS), if taken orally, is expected to self-e... more Background: Self-Emulsifying Drug Delivery System (SEDDS), if taken orally, is expected to self-emulsify in GIT and improve the absorption and bioavailability. Probucol (PB) is a highly lipophilic compound with very low and variable bioavailability. Objective: The objectives of this study were to examine the stability and conduct bioavailability of the prepared Probucol Self-Emulsified Drug Delivery System (PBSEDDS) in human volunteers. Methods: The methods included preparation of different PBSEDDS using soybean oil (solvent), Labrafil M1944CS (surfactant) and Capmul MCM-C8 (co-surfactant). The formulations were characterized in vitro for spontaneity of emulsification, droplet size, turbidity and dissolution in water after packing in HPMC capsules. The optimized formulations were evaluated for stability at different storage temperatures and human bioavailability compared with the drug dissolved in soybean oil (reference). Results: The results showed that formulations (F1-F4) were st...

Journal of drug targeting, 2017

Metformin hydrochloride (MtHCL) is an oral antidiabetic drug and has many other therapeutic benef... more Metformin hydrochloride (MtHCL) is an oral antidiabetic drug and has many other therapeutic benefits. It has poor bioavailability, narrow absorption window and extensive liver metabolism. Moreover, children and elders face difficulty to swallow the commercial oral tablets. Preparation, in vitro/in vivo evaluation of MtHCL suppositories for rectal administration to solve some of these problems. Suppository fatty bases (Witepsol(®), Suppocire(®) and Massa(®); different grades) and PEG bases 1000, 4000 and 6000 (different ratios), were used to prepare rectal suppository formulations each containing 500 mg drug. These were characterized for manufacturing defects, and pharmacotechnical performance and formulations showing superior results were subjected to bioavailability testing in human volunteers compared with the commercial oral tablet (Ref) applying LC-MS/MS developed analytical technique. The preparation method produced suppositories with satisfactory characteristics and free of ma...

Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 2007

To assess and compare the bioavailability of three different oral dosage forms of vitamin A in ra... more To assess and compare the bioavailability of three different oral dosage forms of vitamin A in rats. The formulations included vitamin A self-nanoemulsified drug delivery (SNEDD) optimized formulation-filled capsule (F1), vitamin A SNEDD optimized formulation compressed tablet (F2) and vitamin A oily solution-filled capsules without any additives (control, F3). Bioavailability was assessed after a single oral dose of the three formulations using three groups of rats, each group comprising 6 rats. Blood samples were collected at baseline and over the next 8 h. Plasma was separated and extracted to obtain the drug, which was measured by HPLC. Statistical data analysis was performed using the Student t test and ANOVA with p < 0.05 as the minimal level of significance. From the pharmacokinetic parameters, both F1 and F2 showed improved bioavailability compared to F3. The values of AUC +/- SD were 3,080.7 +/- 190.2, 2,137.1 +/- 130.5 and 1,485.2 +/- 80.1 ng x h/ml for F1, F2 and F3, r...

Die Pharmazie, 2006

The purpose of this work was to study the effect of organic solvent and surfactant type on the in... more The purpose of this work was to study the effect of organic solvent and surfactant type on the in vitro release behavior in general and on the burst release in particular of beta-estradiol from PLA/PLGA microspheres. Also the effect of these variables on the encapsulation efficiency was investigated. The microspheres were prepared by solvent evaporation technique using dichloromethane (DCM), ethyl acetate (EtAc), tetrahydrofuran (THF), chloroform (CHCl3) or acetone (AC) as organic solvent and polyvinyl alcohol (PVA), Tween 80, sodium lauryl sulfate (SLS) or benzalkonium chloride (BKCI) as surfactant. The obtained microspheres were tested for encapsulation efficiency and in vitro drug release using 50% methanol/buffer pH 7.4 as dissolution medium. EtAC and PVA formulations showed the highest encapsulation efficiency and the lowest burst release. These microspheres were further characterized for particle size distribution, SEM and zeta potential. The results suggested that these mater...

PubMed, Sep 1, 2008

The main purposes of this work were to prepare, characterize and optimize a self-emulsified drug ... more The main purposes of this work were to prepare, characterize and optimize a self-emulsified drug delivery system of probucol (PBSEDDS) with enhanced dissolution and better chance for oral absorption. The methods included determination of the solubility of probucol in different oils, surfactants and co-surfactants using saturation solubility method and HPLC for drug analysis. The ingredients showing high drug solubility were used to prepare PBSEDDS after being tested for physical and chemical compatibility with the drug using DSC and FTIR. The prepared formulations were evaluated for droplet size, turbidity, spontaneity of emulsification and dissolution in water. Optimization was performed using a three-factor, three-level Box-Behnken experimental design. The results showed high drug solubility and compatibility with soybean oil (solvent), Labrafil M1944CS (surfactant) and Capmul MCM-C8 (cosurfactant). Oil to surfactant/co-surfactant ratio showed large influence on the characteristics of PBSEDDS. Several fold improvement of drug dissolution was observed compared to drug solution in soybean oil alone. Optimization study showed that observed and predicted values of cumulative percent drug dissolution after 60 min were in reasonable agreement. The experimental design applied helped in understanding the effects and the interaction effects between the independent factors. The prepared PBSEDDS may have the potential to enhance the therapeutic bioavailability of probucol.

Medical Principles and Practice, 2011

Medical Principles and Practice, 2011

Access to full text and tables of contents, including tentative ones for forthcoming issues: www.... more Access to full text and tables of contents, including tentative ones for forthcoming issues: www.karger.com/mpp_issues 60 Diagnostic Yield and Clinical Impact of Capsule Endoscopy in Obscure Gastrointestinal Bleeding during Routine Clinical

Acta Pharmaceutica, 2014

Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobic... more Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobicity and large molecular mass. The aim of the present study was to develop alpha-tocopherol (T) topical formulations and evaluate their ex vivo and in vivo permeation. Franz diffusion cells were used for ex vivo permeation, and neonatal rats were used for in vivo permeation. Seven gel formulations and 21 liquid formulations were investigated for physical stability, viscosity and permeation of T. Analysis of T was performed by a validated HPLC method using a UV detector. The ex vivo permeation from gel and emulsion formulations was very poor (0.001-0.015 %). Highest permeation was observed from monophasic liquid formulations containing dimethyl sulfoxide (DMSO), tocopheryl polyethylene glycols (TPGs), propylene glycol, ethanol and 9.5 % T. The in vivo results demonstrated higher retention in the epidermis compared to subcutaneous tissues, 1377 and 1.13 μg g-1, respectively. Increasing T co...

Ibuprofen (IB) a NSAID, has poor dissolution and many gastrointestinal side effects. Self-Emulsif... more Ibuprofen (IB) a NSAID, has poor dissolution and many gastrointestinal side effects. Self-Emulsifying drug delivery system (SEDDS) has proved its efficacy to improve the solu bility and dissolution of many lipophilic drugs and improve their characteristics. The object ives of this study were to develop, optimize and ch aracterize a IBSEDDS applying Face Centered Experimental Design (FCED). The methods included determination of solubility of IB in different oils, surfactants and co-surfactants. Ingredient showing high drug solub ility were used to formulate several IBSEDDS after being teste d for physical and chemical compatibility with the drug. A three factor, three level FCED was used for the opt imization process. The concentration of oil, surfac tant and cosurfactant were the independent variables, X1, X2 and X3 respectively, while the dissolution, turbid ity and droplet size were the dependent variables, Y1, Y2 a nd Y3 respectively. The results showed high solubil ity and compa...

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.

International Journal of Pharmaceutics, 2002

The objectives of the present study were (1) to evaluate the effect of formulation ingredients on... more The objectives of the present study were (1) to evaluate the effect of formulation ingredients on the release rate of Ubiquinone from its adsorbing solid compact; and (2) to prepare and evaluate an optimized self-nanoemulsified tablet formulation. A three factor, three-level Box-Behnken design was used for the optimization procedure, with the amounts of copolyvidone (X 1), maltodextrin (X 2) and microcrystalline cellulose (X 3) as the independent variables. The response variable was cumulative percent of Ubiquinone emulsified in 45 min with constraints on weight, flowability index, tensile strength, friability and disintegration time of the dry powdered emulsion and the resultant compact. Based on the experimental design, different Ubiquinone release rates and profiles were obtained. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the cumulative percent emulsified in 45 min was Y 6 = 64.10− 12.32X 1 − 4.36X 2 − 25.53X 3 + 6.99X 1 X 2 +3.97X 1 X 3 + 9.70X 2 X 3 −8.98X 1 2 −16.22X 2 2 + 17.10X 3 2. The optimization model predicted an 85.4% release with X 1 , X 2 and X 3 levels of 66.6, 560.1 and 100, respectively. A new formulation was prepared according to these levels. The observed responses were in close agreement with the predicted values of the optimized formulation.

Pharmazie

The main purposes of this work were to prepare, characterize and optimize a self-emulsified drug ... more The main purposes of this work were to prepare, characterize and optimize a self-emulsified drug delivery system of probucol (PBSEDDS) with enhanced dissolution and better chance for oral absorption. The methods included determination of the solubility of probucol in different oils, surfactants and co-surfactants using saturation solubility method and HPLC for drug analysis. The ingredients showing high drug solubility were used to prepare PBSEDDS after being tested for physical and chemical compatibility with the drug using DSC and FTIR. The prepared formulations were evaluated for droplet size, turbidity, spontaneity of emulsification and dissolution in water. Optimization was performed using a three-factor, three-level Box-Behnken experimental design. The results showed high drug solubility and compatibility with soybean oil (solvent), Labrafil M1944CS (surfactant) and Capmul MCM-C8 (cosurfactant). Oil to surfactant/co-surfactant ratio showed large influence on the characteristic...

Pharmazie

The purposes of this study were to assess the mucoadhesion and bioavailability and their correlat... more The purposes of this study were to assess the mucoadhesion and bioavailability and their correlation for ketoprofen tablet dosage forms (F1-F6) containing polycarbophil (PC), sodium carboxymethylcellulose (Na CMC) as bioadhesives, Avicel pH 101 as direct compressible tablet vehicle or mixtures of these, and non compressible vehicles such as lactose and starch. For mucoadhesion assessment, we used sheep gastric mucosa and for bioavailability we used six human volunteers in an open randomized seven-way crossover study. Young's modulus (YM) and relative bioavailability (RB) parameters were used for evaluation of mucoadhesion and bioavailability, respectively. The results indicated that F2 containing Na CMC (72.5%) showed the highest value of YM (7.6 +/- 0.76 pascals) and 119.4 +/- 3.2% for RB. Decreasing the amount of Na CMC to 10% in F3 and F6 decreased the values of YM and RB to 1.4 +/- 0.08 and 84 +/- 2.05 in F3, 4.6 +/- 0.43 and 114.7 +/- 2.46 in F6, respectively. The highest R...

Drug discoveries & therapeutics, 2008

The aim of the present study was to use factorial design to enhance the dissolution rate of nimes... more The aim of the present study was to use factorial design to enhance the dissolution rate of nimesulide using solid binary systems with the hydrophilic carriers D-mannitol and polyethylene glycol (PEG 4000). Two-factor full factorial design was employed to investigate the effects of the drug/carrier ratio (X(1), 10 and 20%) and the method of preparation (X(2), physical or co-melted mixture) on the percent drug release after 60 min (Y(1)). Drugcarrier co-melted mixtures were prepared by melting the carriers D-mannitol or PEG with the drug. For physical mixtures, the drug and carrier were mixed thoroughly in a mortar until a homogeneous mixture was obtained. Drug-carrier interactions were investigated by differential scanning calorimetry (DSC). All prepared mixtures were filled in hard gelatin capsules, size 0, and then their dissolution rate was tested. The results showed an increase in the solubility of the drug with increasing polymer concentrations. Thermal analysis revealed no not...

Die Pharmazie, 2001

Old and recent reports show that honey has beneficial effects on the skin as antiseptic for wound... more Old and recent reports show that honey has beneficial effects on the skin as antiseptic for wounds, burns and ulcers and as a healing promoter. Many investigators confirmed the usefulness of honey in the treatment of skin infections as well as internal diseases. The factors behind these effects are not completely explained. The aim of this study is: a) to investigate the antimicrobial activity of crude honey, b) to separate the fractions responsible for its activity, c) to formulate the honey extract as semisolid dosage forms, d) to study its release, and e) to determine its stability. The results showed that the ethylacetate honey extract showed antibacterial, anticandida and antifungal effects at low concentration. The release of honey extract from different ointment bases was depending on the constituents of the base, and its stability was found to be temperature and base dependent.

Die Pharmazie, 2001

A novel method was developed for the quantitative determination of ubidecarenone (CoQ10) in aqueo... more A novel method was developed for the quantitative determination of ubidecarenone (CoQ10) in aqueous media using non aqueous reversed phase liquid chromatography. Standards were prepared by melting the compound in Cremophor EL followed by dilution with distilled water. Samples were then analyzed by a Reverse Phase HPLC method using a Waters Novapak C18, 3.9 x 150 mm column. The mobile phase used was methanol: n-hexane (9:1) at a flow rate of 1.5 ml/min. Response of the detector to the analyte was linear (r: 0.999) over the range of 2.5-100 micrograms ml-1, with a limit of detection of 0.17 microgram ml-1. Acetone used to solubilize CoQ10 in the surfactant and Cremophor EL did not interfere with sample analysis. This method provided a convenient and alternative approach to the existing methods that require organic solvent extractions prior to analysis. Besides, this method enabled the separation of major photolytic decomposition products of CoQ10.

Die Pharmazie, 2001

The objectives of the present study were to screen the formulation and process variables for the ... more The objectives of the present study were to screen the formulation and process variables for the preparation of extended release naproxen tablets with Eudragit L100-55. The tablets were prepared by compression of microspheres that were obtained by a coprecipitation technique. The process involved dissolution of naproxen and Eudragit L 100-55 in alcohol USP followed by the addition of an aqueous solution containing a surfactant and deaggregating agents. The mixture was stirred for a specified time period to obtain microspheres, which were filtered and air-dried to a constant weight. The microspheres were then compressed to obtain plain tablets with a diameter of 12 mm. A 7-factor 12-run Plackett-Burman screening design was employed to evaluate the main effects of homogenization time (X1), rate of water addition (X2), amount of polymer (X3), amount of precipitating solution (X4), concentration of electrolytes (X5), compression pressure (X6), and the concentration of lubricant (X7) on ...

The authors evaluate the effect of microcrystalline cellulose (MCC) on the tableting performance,... more The authors evaluate the effect of microcrystalline cellulose (MCC) on the tableting performance, surface roughness, and dissolution properties of a dry adsorbed self-nanoemulsified powdered formulation. Heckel analysis was used to study the tabletability, compressibility, and compactibility of six formulas prepared with various MCC grades. Surface topography revealed a higher degree of waviness at the lower surface of the compacts as the result of granule segregation. The dissolution rate of the nanoemulsion from the tablets increased with increasing MCC particle size. Good flow properties of the formulations resulted from the granular nature of the mixtures. Low hardness and friability indicated oil-induced bridging between the particles.

Pharmaceutical Development and Technology, 2006

The purpose of this work was to evaluate the main and interaction effects of formulation factors ... more The purpose of this work was to evaluate the main and interaction effects of formulation factors on the drug encapsulation efficiency of beta-estradiol biodegradable microspheres by applying response surface methodology. A secondary purpose was to obtain an optimized formula for long-term therapy of osteoporosis. A three factor, three level Box-Behnken experimental design was used to get 15 experimental runs. The independent variables were drug/polymer ratio (X1), dispersing agent concentration (X2), and deaggregating agent concentration (X3). The dependent variables were percentage encapsulation efficiency (Y1), cumulative percent drug released (Y2), and percentage yield of the microspheres (Y3). The formulations were prepared by emulsion solvent evaporation technique using ethyl acetate as organic solvent. The optimized formulation was maximized for encapsulation efficiency and further characterized for the particle size distribution, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FT-IR). The mathematical relationship obtained between X1, X2, X3, and Y1 was: Y1 = -129.85 + 29.35X1 + 129.99X2 + 64.82X3 - 3.2X1X2 - 0.29X1X3 - 35.83X2X3 - 2.05X(2)(1) - 13.23X(2)(2) - 5.92X(2)(3) (R2 = 0.99) The equation showed that X1, X2, and X3 affect Y1 positively but interaction between any two of these factors affects Y1 negatively. The most significant interaction was between X2 and X3. The finding indicated that controlled releases beta-estradiol biodegradable microspheres with high encapsulation efficiency and low pulsatile release can be prepared and the quantitative response surface methodology applied helped in understanding the effects and the interaction effects between the three factors applied.

Journal of Pharmaceutical and Biomedical Analysis, 2003

An isocratic reversed phase high-performance liquid chromatographic (HPLC) method with ultraviole... more An isocratic reversed phase high-performance liquid chromatographic (HPLC) method with ultraviolet detection at 205 nm has been developed for the determination of cyclosporin-A (CyA) in rat blood and plasma. Naproxen was successfully used as an internal standard. Blood or plasma samples were pretreated by liquid–liquid extraction with diethyl ether. The ether extract was evaporated and the residue was reconstituted in

Current Drug Delivery, 2018

Background: Self-Emulsifying Drug Delivery System (SEDDS), if taken orally, is expected to self-e... more Background: Self-Emulsifying Drug Delivery System (SEDDS), if taken orally, is expected to self-emulsify in GIT and improve the absorption and bioavailability. Probucol (PB) is a highly lipophilic compound with very low and variable bioavailability. Objective: The objectives of this study were to examine the stability and conduct bioavailability of the prepared Probucol Self-Emulsified Drug Delivery System (PBSEDDS) in human volunteers. Methods: The methods included preparation of different PBSEDDS using soybean oil (solvent), Labrafil M1944CS (surfactant) and Capmul MCM-C8 (co-surfactant). The formulations were characterized in vitro for spontaneity of emulsification, droplet size, turbidity and dissolution in water after packing in HPMC capsules. The optimized formulations were evaluated for stability at different storage temperatures and human bioavailability compared with the drug dissolved in soybean oil (reference). Results: The results showed that formulations (F1-F4) were st...

Journal of drug targeting, 2017

Metformin hydrochloride (MtHCL) is an oral antidiabetic drug and has many other therapeutic benef... more Metformin hydrochloride (MtHCL) is an oral antidiabetic drug and has many other therapeutic benefits. It has poor bioavailability, narrow absorption window and extensive liver metabolism. Moreover, children and elders face difficulty to swallow the commercial oral tablets. Preparation, in vitro/in vivo evaluation of MtHCL suppositories for rectal administration to solve some of these problems. Suppository fatty bases (Witepsol(®), Suppocire(®) and Massa(®); different grades) and PEG bases 1000, 4000 and 6000 (different ratios), were used to prepare rectal suppository formulations each containing 500 mg drug. These were characterized for manufacturing defects, and pharmacotechnical performance and formulations showing superior results were subjected to bioavailability testing in human volunteers compared with the commercial oral tablet (Ref) applying LC-MS/MS developed analytical technique. The preparation method produced suppositories with satisfactory characteristics and free of ma...

Medical principles and practice : international journal of the Kuwait University, Health Science Centre, 2007

To assess and compare the bioavailability of three different oral dosage forms of vitamin A in ra... more To assess and compare the bioavailability of three different oral dosage forms of vitamin A in rats. The formulations included vitamin A self-nanoemulsified drug delivery (SNEDD) optimized formulation-filled capsule (F1), vitamin A SNEDD optimized formulation compressed tablet (F2) and vitamin A oily solution-filled capsules without any additives (control, F3). Bioavailability was assessed after a single oral dose of the three formulations using three groups of rats, each group comprising 6 rats. Blood samples were collected at baseline and over the next 8 h. Plasma was separated and extracted to obtain the drug, which was measured by HPLC. Statistical data analysis was performed using the Student t test and ANOVA with p < 0.05 as the minimal level of significance. From the pharmacokinetic parameters, both F1 and F2 showed improved bioavailability compared to F3. The values of AUC +/- SD were 3,080.7 +/- 190.2, 2,137.1 +/- 130.5 and 1,485.2 +/- 80.1 ng x h/ml for F1, F2 and F3, r...

Die Pharmazie, 2006

The purpose of this work was to study the effect of organic solvent and surfactant type on the in... more The purpose of this work was to study the effect of organic solvent and surfactant type on the in vitro release behavior in general and on the burst release in particular of beta-estradiol from PLA/PLGA microspheres. Also the effect of these variables on the encapsulation efficiency was investigated. The microspheres were prepared by solvent evaporation technique using dichloromethane (DCM), ethyl acetate (EtAc), tetrahydrofuran (THF), chloroform (CHCl3) or acetone (AC) as organic solvent and polyvinyl alcohol (PVA), Tween 80, sodium lauryl sulfate (SLS) or benzalkonium chloride (BKCI) as surfactant. The obtained microspheres were tested for encapsulation efficiency and in vitro drug release using 50% methanol/buffer pH 7.4 as dissolution medium. EtAC and PVA formulations showed the highest encapsulation efficiency and the lowest burst release. These microspheres were further characterized for particle size distribution, SEM and zeta potential. The results suggested that these mater...