Mohamed Nasr - Academia.edu (original) (raw)

Papers by Mohamed Nasr

Research paper thumbnail of Custom fractional factorial designs to develop atorvastatin self-nanoemulsifying and nanosuspension delivery systems – enhancement of oral bioavailability

Drug Design, Development and Therapy, 2015

Poor water solubility of a drug is a major challenge in drug delivery research and a main cause f... more Poor water solubility of a drug is a major challenge in drug delivery research and a main cause for limited bioavailability and pharmacokinetic parameters. This work aims to utilize custom fractional factorial design to assess the development of self-nanoemulsifying drug delivery systems (SNEDDS) and solid nanosuspensions (NS) in order to enhance the oral delivery of atorvastatin (ATR). According to the design, 14 experimental runs of ATR SNEDDS were formulated utilizing the highly ATR solubilizing SNEDDS components: oleic acid, Tween 80, and propylene glycol. In addition, 12 runs of NS were formulated by the antisolvent precipitationultrasonication method. Optimized formulations of SNEDDS and solid NS, deduced from the design, were characterized. Optimized SNEDDS formula exhibited mean globule size of 73.5 nm, zeta potential magnitude of-24.1 mV, and 13.5 μs/cm of electrical conductivity. Optimized solid NS formula exhibited mean particle size of 260.3 nm, 7.4 mV of zeta potential, and 93.2% of yield percentage. Transmission electron microscopy showed SNEDDS droplets formula as discrete spheres. The solid NS morphology showed flaky nanoparticles with irregular shapes using scanning electron microscopy. The release behavior of the optimized SNEDDS formula showed 56.78% of cumulative ATR release after 10 minutes. Solid NS formula showed lower rate of release in the first 30 minutes. Bioavailability estimation in Wistar albino rats revealed an augmentation in ATR bioavailability, relative to ATR suspension and the commercial tablets, from optimized ATR SNEDDS and NS formulations by 193.81% and 155.31%, respectively. The findings of this work showed that the optimized nanocarriers enhance the oral delivery and pharmacokinetic profile of ATR.

Research paper thumbnail of In vitro and in vivo evaluation of cubosomes containing 5-fluorouracil for liver targeting

Acta Pharmaceutica Sinica B, 2015

The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic antic... more The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil (5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer. Cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly (Po 0.05) increased 5-FU liver concentration, a value approximately 5-fold greater than that observed with a 5-FU solution. However, serum serological results and histopathological findings revealed greater hepatocellular damage in rats treated with cubosomal formulation. These results demonstrate the successful development of cubosomal nanoparticles containing 5-FU for liver targeting. However, further studies are required to evaluate hepatotoxicity and in vivo antitumor activity of lower doses of 5-FU cubosomal formulation in treatment of liver cancer.

Research paper thumbnail of Albendazole-loaded cubosomes interrupt the ERK1/2-HIF-1α-p300/CREB axis in mice intoxicated with diethylnitrosamine: A new paradigm in drug repurposing for the inhibition of hepatocellular carcinoma progression

Biomedicine & Pharmacotherapy

Hepatocellular carcinoma (HCC) is a leading cause of cancer related deaths worldwide. It was sugg... more Hepatocellular carcinoma (HCC) is a leading cause of cancer related deaths worldwide. It was suggested that albendazole (ABZ) is a powerful inhibitor of several carcinoma types. However, the bioavailability of ABZ is very poor. Additionally, the mechanisms underlying the antitumor effects of ABZ may go beyond its tubulin-inhibiting activity. Therefore, we aimed to examine the effects of ABZ suspension (i.p. and p.o.) and ABZ-loaded cubosomes (LC) on the diethylnitrosamine-induced HCC in mice. ABZ-loaded nanoparticles exhibited a mean particle size of 48.17 ± 0.65 nm and entrapped 93.26 ± 2.48% of ABZ. The in vivo absorption study confirmed a two-fold improvement in the relative bioavailability compared with aqueous ABZ suspension. Furthermore, the oral administration of ABZ cubosomal dispersion demonstrated regression of tumor production rates that was comparable with ABZ (i.p.). ABZ relieved oxidative stress, improved liver function, and decreased necroinflammation score. The antiangiogenic activity was evident as ABZ effectively downregulated tissue expression of CD34, mRNA expression of CD309 and VEGF at the protein expression level. Besides, lower levels of MMP-9 and CXCR4 indicated antimetastatic activity. ABZ showed a considerable level of apoptotic activity as indicated by increased mRNA expression level of p53 and the increased Bax/BCL-2 ratio and active caspase-3. Additionally, Ki-67 expression levels were downregulated showing an antiproliferative potential. These protective effects contributed to increasing survival rate of diethylnitrosamine-treated mice. These effects found to be mediated via interrupting ERK1/2-HIF-1α-p300/CREB interactions. Therefore, our findings revealed that disrupting ERK1/2-HIF-1α-p300/CREB interplay might create a novel therapeutic target for the management of HCC.

Research paper thumbnail of Development and characterization of solid lipid nanoparticles loaded with …

International journal of …

This paper describes the preparation of colloidal lipid particles containing magnetite from warm ... more This paper describes the preparation of colloidal lipid particles containing magnetite from warm emulsions. A two step method was used to obtain the nanoparticles: (i) formulation of a transparent phase by heating a O/W emulsion (aqueous surfactant solution melted with a lipid phase, ...

Research paper thumbnail of Preparation and Evaluation of Iron Oxide Nanoparticles for Treatment of Iron Deficiency Anemia

International Journal of Pharmacy and Pharmaceutical Sciences

Objective: The objective of this research was to formulate and evaluate iron oxide nanoparticles ... more Objective: The objective of this research was to formulate and evaluate iron oxide nanoparticles for treatment of iron deficiency anemia (IDA).Methods: Iron oxide nanoparticles were prepared by co-precipitation method and stabilized by coating with folic acid or chitosan. The prepared nanoparticles were characterized in vitro for morphology, particle size, zeta potential, crystallinity and ultraviolet-visible (UV-Vis) absorption. In vivo studies were performed to evaluate the efficacy of the prepared nanoparticles in treating iron-deficient anemic rats compared to the commercial iron product.Results: In vitro results revealed that particle sizes were 65.95±5 nm, 220.2±12 nm and 295.3±19 nm for uncoated iron oxide nanoparticles, folic acid-coated iron oxide nanoparticles and chitosan coated iron oxide nanoparticles, respectively. UV-Vis absorption spectrum and x-ray diffraction (XRD) patterns confirmed that the prepared nanoparticles were iron oxide nanoparticles. In vivo results ind...

Research paper thumbnail of Formulation and clinical evaluation of mucoadhesive buccal films containing hyaluronic acid for treatment of aphthous ulcer

Journal of Drug Delivery Science and Technology

Abstract Hyaluronic acid (HA), a linear polymer of glucuronic acid N acetyl glucosamine disacchar... more Abstract Hyaluronic acid (HA), a linear polymer of glucuronic acid N acetyl glucosamine disaccharide, has tissue healing properties and is used for treatment of oral ulcers. This study aims to develop a controlled release mucoadhesive buccal film containing HA as a novel delivery system to overcome the drawbacks of the fast wash off of mouth rinses and gels used for treatment of aphthous ulcers. HA films are prepared by applying freeze and thaw cross linking technique. A full 21 × 31 × 41 factorial design was applied to study the effect of three independent variables namely polymer type, polymer concentration and the number of freeze/thaw cycles on the selected dependent variables of tensile strength, mucoadhesion and time required to release 50% of HA (T50%). The prepared HA films were evaluated for their physicochemical properties including folding endurance, surface pH, thickness, mucoadhesion properties, tensile strength and in vitro drug release. The optimum formula was evaluated for its clinical efficiency in treatment of patients have aphthous ulcer. The obtained results (good physical properties, mechanical properties (high TS), mucoadhesion properties and controlled release (high t50%)) indicated that an optimum formula for controlled release mucoadhesive buccal film which is aimed to be effective, safe and stable when used in treatment of aphthous ulcers. After clinical study, it was observed that the formulation of the hyaluronic acid resulted in a more potent effect and resistance to the washing effect of saliva and friction from food. The efficacy of hyaluronic acid was greatly affected by formulation which allowing for prolonged contact.

Research paper thumbnail of Formulation and Characterization of Cubosomes Containing REB for Improvement of Oral Absorption of the Drug in Human Volunteers

Journal of Advanced Pharmacy Research

Objective: To prepare rebamipide (REB)-loaded cubosomal nanoparticles to improve the oral bioavai... more Objective: To prepare rebamipide (REB)-loaded cubosomal nanoparticles to improve the oral bioavailability of the drug in human volunteers. Methodology: The poorly water soluble drug REB was incorporated into cubosomal nanoparticles by solvent dilution method. The prepared REB-loaded cubosomes were in vitro characterized for particle size, polydispersity index (PDI), zeta potential, drug crystallinity and in vitro drug release. In vivo absorption of REB-loaded cubosomes was compared with drug powder and commercially available tablets Mucosta ® (Egypt Otsuka Pharmaceutical Company) in healthy human volunteers. Results: In vitro, REB-loaded cubosomes entrapped about 82.44 % drug and revealed nanometer-size ranged from 303.1 ± 4.9 to 444.9 ± 6 nm. In vitro REB release from cubosomes exhibited a phase of rapid and high release of the drug during the first hour followed by a slower and complete drug release over a period of 3 hrs. The results of bioavailability study in healthy human volunteers showed that cubosomes significantly improved the rate and extent of REB absorption. The mean relative bioavailability of the REB loaded cubosomes compared to the drug powder and commercially available tablets (Mucosta ®) was 267.67 % and 166.29 % respectively. Conclusion: The prepared cubosomes significantly improved the In-vivo absorption of REB in comparison with drug powder and commercially available tablets (Mucosta ®).

Research paper thumbnail of In vivo Absorption Study of Solid Dispersion Containing Atorvastatin Calcium in Human Volunteers

Journal of Advanced Pharmacy Research

Objectives: Solid dispersion is a unique and promising approach for improving the oral absorption... more Objectives: Solid dispersion is a unique and promising approach for improving the oral absorption and oral bioavailability of the poorly water soluble drugs. Atorvastatin Calcium (ATV) is an anti-hyper lipidemic agent, It belongs to class II drugs according to the biopharmaceutical classification system (BCS), and undergoes extensive first-pass metabolism after oral absorption exhibiting 12% bioavailability. The Objective of the present study is to investigate the effect of formulating the hydrophobic drug (ATV) in a solid dispersion form on its bioavailability. Methods: ATV solid dispersion (ATV-SD) was prepared by microwave induced fusion method, containing poloxamer188 as a hydrophillic carrier. The resultant ATV-SD was compressed into tablets with other ingredients and was evaluated against pure ATV tablets, in vitro dissolution study was carried out to compare the dissolution profiles of the prepared ATV-SD against the pure form of ATV. In vivo study was conducted using healthy male volunteers (n = 6). A high performance liquid chromatography method was employed to determine the level of drug in human plasma. Results: In vitro dissolution study revealed an enhancement in the dissolution profile of ATV-SD. The study of pharmacokinetics parameters also showed an enhancement after oral administration of ATV-SD tablet when compared with pure ATV tablets, where , the AUC0-60h and Cmax were increased after intake of ATV-SD tablets orally compared with that of pure ATV tablets. Conclusion: All these could be demonstrated that ATV-SD would be prospective means for enhancing higher oral bioavailability of ATV.

Research paper thumbnail of Influence of siRNA Loaded Nanoparticles on the Metastasis and Growth Rate of Cancer Cell Lines

Journal of Advanced Pharmacy Research

Objectives: The aim of this study was to investigate the ability of siRNA-loaded nanoparticles to... more Objectives: The aim of this study was to investigate the ability of siRNA-loaded nanoparticles to control the capability of cisplatin-resistant cell lines to decrease cancer metastasis and cell proliferation rate. Methods: The effect of siRNAloaded NPs on the migratory (metastasis) and proliferation (cell growth rate) activity of cisplatin-resistant cell lines compared to untreated cells was investigated using the wound healing assay and cell growth rate assay, respectively. Results: The results showed that cells were treated with siRNA-loaded nanoparticles after 24 h from starting the scratch, succeeded to cover of 59 ± 12.9, and 30 ± 6.1% only from the wound for cell line Cis 1R and Cis 12R, respectively. On the other hand of the untreated cells that were treated with positive control nanoparticles showed complete healing for the wound within the same period of time. Results of cell proliferation of both cell lines exhibited significantly (P≤ 0.001) lower growth rate after treatment with loaded nanoparticles compared to positive control nanoparticles and untreated cells. Conclusion: The obtained results indicated that siRNA-loaded nanoparticles succeeded to not only reduce metastasis but also decrease cell proliferation rate of cisplatin-resistant cell lines.

Research paper thumbnail of Comparison of drug release from liquid crystalline monoolein dispersions and solid lipid nanoparticles using a flow cytometric technique

Acta pharmaceutica Sinica. B, 2016

Colloidal lipid particles such as solid lipid nanoparticles and liquid crystalline nanoparticles ... more Colloidal lipid particles such as solid lipid nanoparticles and liquid crystalline nanoparticles have great opportunities as drug carriers especially for lipophilic drugs intended for intravenous administration. In order to evaluate drug release from these nanoparticles and determine their behavior after administration, emulsion droplets were used as a lipophilic compartment to which the transfer of a model drug was measured. The detection of the model drug transferred from monoolein cubic particles and trimyristin solid lipid nanoparticles into emulsion droplets was performed using a flow cytometric technique. A higher rate and amount of porphyrin transfer from the solid lipid nanoparticles compared to the monoolein cubic particles was observed. This difference might be attributed to the formation of a highly ordered particle which leads to the expulsion of drug to the surface of the crystalline particle. Furthermore, the sponge-like structure of the monoolein cubic particles decre...

Research paper thumbnail of In Vitro and In Vivo Evaluation of Combined Time and pH- Dependent Oral Colonic Targeted Prednisolone Microspheres

British Journal of Pharmaceutical Research, 2013

Research paper thumbnail of Preparation, Characterization and Therapeutic Activity of Gliclazide Β-Cyclodextrin Inclusion Complex

ABSTRACT The objective of this study was to improve therapeutic activity of gliclazide by improvi... more ABSTRACT The objective of this study was to improve therapeutic activity of gliclazide by improving its aqueous solubility through preparation of inclusion complex between gliclazide and ß-cyclodextrin. Gliclazide ß-cyclodextrin solid complex was prepared with equimolar ratio of both gliclazide and ß-cyclodextrin in presence or absence of water soluble polymers (PVP-K15 and HPMC) using co-evaporation, spray drying and freeze drying techniques. The prepared solid complexes were characterized by DSC, IR, XRD and dissolution testing in comparison with the pure gliclazide powder. The solid complexes prepared by spray drying, freeze drying and co-evaporation in presence of hydrophilic polymers showed a prompt drug release compared to pure gliclazide (P < 0.05). The spry dried complex in presence of PVP-K15 showed the highest drug release after 5 and 90 min and significantly increased the % dissolution efficiency (P < 0.05) compared to the pure drug. Moreover, in vivo assessment of ...

Research paper thumbnail of Optimized zein nanospheres for improved oral bioavailability of atorvastatin

International Journal of Nanomedicine, 2015

Background: This work focuses on the development of atorvastatin utilizing zein, a natural, safe,... more Background: This work focuses on the development of atorvastatin utilizing zein, a natural, safe, and biocompatible polymer, as a nanosized formulation in order to overcome the poor oral bioavailability (12%) of the drug. Methods: Twelve experimental runs of atorvastatin-zein nanosphere formula were formulated by a liquid-liquid phase separation method according to custom fractional factorial design to optimize the formulation variables. The factors studied were: weight % of zein to atorvastatin (X 1), pH (X 2), and stirring time (X 3). Levels for each formulation variable were designed. The selected dependent variables were: mean particle size (Y 1), zeta potential (Y 2), drug loading efficiency (Y 3), drug encapsulation efficiency (Y 4), and yield (Y 5). The optimized formulation was assayed for compatibility using an X-ray diffraction assay. In vitro diffusion of the optimized formulation was carried out. A pharmacokinetic study was also done to compare the plasma profile of the atorvastatin-zein nanosphere formulation versus atorvastatin oral suspension and the commercially available tablet. Results: The optimized atorvastatin-zein formulation had a mean particle size of 183 nm, a loading efficiency of 14.86%, and an encapsulation efficiency of 29.71%. The in vitro dissolution assay displayed an initial burst effect, with a cumulative amount of atorvastatin released of 41.76% and 82.3% after 12 and 48 hours, respectively. In Wistar albino rats, the bioavailability of atorvastatin from the optimized atorvastatin-zein formulation was 3-fold greater than that from the atorvastatin suspension and the commercially available tablet. Conclusion: The atorvastatin-zein nanosphere formulation improved the oral delivery and pharmacokinetic profile of atorvastatin by enhancing its oral bioavailability.

Research paper thumbnail of In Vitro and In Vivo Evaluation of Oxatomide β-Cyclodextrin Inclusion Complex

Journal of Pharmaceutics, 2013

The objective of this study was to evaluate the influence of oxatomide β-cyclodextrin inclusion c... more The objective of this study was to evaluate the influence of oxatomide β-cyclodextrin inclusion complex on the physicochemical properties and bioavailability of the drug. Oxatomide β-cyclodextrin solid complex was prepared with equimolar ratio of both oxatomide and β-cyclodextrin in presence or absence of water soluble polymers using different techniques. The coevaporated complex prepared in presence of PVP-K15 showed a prompt drug release and significantly increased % dissolution efficiency compared to the pure oxatomide. Moreover, the results of bioavailability evaluation of this complex in rabbits compared to commercial drug product indicated a 73.15% increase in the oral bioavailability of oxatomide. In conclusion, inclusion complex of oxatomide with β-cyclodextrin prepared by coevaporation in presence of PVP-K15 not only results in an enhancement of the oxatomide dissolution rate but also improves the bioavailability of oxatomide.

Research paper thumbnail of Formulation and evaluation of mastic gum as a compression coat for colonic delivery of 5-flurouracil

International Journal of Drug Delivery, 2011

Mastic gum has been reported to possess considerable anti-tumor activity against human colorectal... more Mastic gum has been reported to possess considerable anti-tumor activity against human colorectal cancer. The purpose of this work was to evaluate mastic gum in formulation of colon-specific 5-flurouracil delivery system for effective treatment of ...

Research paper thumbnail of In vitrocytotoxicity and bioavailability of solid lipid nanoparticles containing tamoxifen citrate

Pharmaceutical Development and Technology, 2014

The objective of this study was to evaluate the influence of solid lipid nanoparticles (SLN) load... more The objective of this study was to evaluate the influence of solid lipid nanoparticles (SLN) loaded with the poorly water-soluble drug tamoxifen citrate (TC) on the in vitro antitumor activity and bioavailability of the drug. TC-loaded SLN were prepared by solvent injection method using glycerol monostearate (GMS) or stearic acid (SA) as lipid matrix. Poloxamer 188 or tween 80 were used as stabilizers. TC-loaded SLN (F3 and F4) prepared using GMS and stabilized by poloxamer 188 showed highest entrapment efficiency % (86.07 ± 1.74 and 90.40 ± 1.22%) and reasonable mean particle sizes (130.40 ± 9.45 and 243.80 ± 12.33 nm), respectively. The in vitro release of TC from F3 and F4 exhibited an initial burst effect followed by a sustained drug release. In vitro cytotoxicity of F3 against human breast cancer cell line MCF-7 showed comparable antitumor activity to free drug. Moreover, the results of bioavailability evaluation of TC-loaded SLN in rats compared to free TC indicated that 160.61% increase in the oral bioavailability of TC. The obtained results suggest that incorporation of the poorly water-soluble drug TC in SLN preserves the in vitro antitumor activity and significantly enhance oral bioavailability of TC in rats.

Research paper thumbnail of Guar gum and hydroxy propyl methylcellulose compressed coated tablets for colonic drug delivery: in vitro and in vivo evaluation in healthy human volunteers

Drug Discoveries & Therapeutics, 2011

The objectives of the present study are to evaluate guar gum in combination with hydroxy propyl m... more The objectives of the present study are to evaluate guar gum in combination with hydroxy propyl methylcellulose (HPMC) as compression coat for colonic delivery of prednisolone as well as improving the mechanical properties of the compressed coated tablets. The core tablets containing 5 mg prednisolone were compression coated with 125 mg of coating materials consisted of guar gum alone or mixtures of guar gum in combination with different ratios of HPMC. The compressed coated tablets were evaluated for their mechanical properties, in vitro drug release and in vivo performance in human volunteers. The compressed coated tablets with coats containing HPMC exhibited acceptable mechanical properties. In vitro drug release studies in pH 7.4 phosphate-buffered saline medium containing 2% (w/v) rat caecal content have shown that increase in concentration of HPMC in the prepared coats from 10% to 20% resulted in an increase in the release rate. However, further increase in HPMC concentration to constitute 30% caused a reduction in the release rate. Based on the drug release results, tablets coated with coat consisted of 80% guar gum and 20% HPMC were selected for in vivo evaluation. In vivo gamma scintigraphic study on human volunteers using technetium-99m-diethylenetriamine pentaacetic acid as a tracer was performed. The results showed that tablets remained intact in stomach and small intestine, however partial and complete release of the tracer occurred in the colon. In conclusion, guar gum in combination with HPMC would be successfully used as a carrier for drug delivery to the colon.

Research paper thumbnail of Formulation, Characterization, and Clinical Evaluation of Microemulsion Containing Clotrimazole for Topical Delivery

AAPS PharmSciTech, 2011

The objective of the present study was to formulate and evaluate microemulsion systems for topica... more The objective of the present study was to formulate and evaluate microemulsion systems for topical delivery of clotrimazole (CTM). The solubility of CTM in various oils was determined to select the oil phase of the microemulsion systems. Pseudoternary phase diagrams were constructed to identify the area of microemulsion existence. Five CTM microemulsion formulations (M1-M5) were prepared and evaluated for their thermodynamic stability, pH, refractive index, droplet size, viscosity, and in vitro release across cellulose membrane. Among the prepared microemulsion formulations, M3 (lemon oil/ Tween 80/n-butanol/water) and M4 (isopropyl myristate/Tween 80/n-butanol/water) microemulsion systems were found to be promising according to their physical properties and CTM cumulative percentage release. Gel form of M3 and M4 were prepared using 1% Carbopol 940 as the hydrogel matrix. Both formulations were evaluated in the liquid and gel forms for drug retention in the skin in comparison to the marketed CTM topical cream and their stability examined after storage at 40°C for 6 months. Microemulsion formulations achieved significantly higher skin retention for CTM over the CTM cream. Stability studies showed that M4 preparations were more stable than M3. The in vitro antifungal activity of M4 against Candida albicans was higher than that of the conventional cream. Moreover, clinical evaluation proved the efficacy and tolerability of this preparation in the treatment of various topical fungal infections.

Research paper thumbnail of In Vitro and In Vivo Evaluation of Proniosomes Containing Celecoxib for Oral Administration

AAPS PharmSciTech, 2010

The objectives of this research were to prepare celecoxib proniosomes and evaluate the influence ... more The objectives of this research were to prepare celecoxib proniosomes and evaluate the influence of proniosomal formulation on the oral bioavailability of the drug in human volunteers. A new proniosomal delivery system for a poorly water-soluble drug such as celecoxib was developed and subjected to in vitro and in vivo studies. Proniosomes were prepared by sequential spraying method, which consisted of cholesterol, span 60, and dicetyl phosphate in a molar ratio of 1:1: 0.1, respectively. The average entrapment percent of celecoxib proniosome-derived niosomes was about 95%. The prepared proniosomes showed marked enhancement in the dissolution of celecoxib as compared to pure drug powder. The bioavailability of 200 mg single dose of both celecoxib proniosomal formulation and a conventional marketed celecoxib capsule was studied in human volunteers. The obtained results show that the proniosomal formulation significantly improved the extent of celecoxib absorption than conventional capsule. The mean relative bioavailability of the proniosomal formulation to the conventional capsule was 172.06±0.14%. The mean T max for celecoxib was prolonged when given as proniosomal capsule. There was no significant difference between the values of K el and t 1/2 for both celecoxib preparations. In conclusion, the proniosomal oral delivery system of celecoxib with improved bioavailability was established.

Research paper thumbnail of Influence of Microcrystal Formulation on In Vivo Absorption of Celecoxib in Rats

AAPS PharmSciTech, 2013

The objective of this study was to prepare celecoxib microcrystals using different stabilizers in... more The objective of this study was to prepare celecoxib microcrystals using different stabilizers in order to evaluate the influence of microcrystal formulation on the in vitro dissolution rate and in vivo absorption after oral administration of celecoxib in rats. Three celecoxib microcrystals (MC1, MC2, and MC3) were prepared using solvent change method. Microcrystals were evaluated for morphology, particle size, crystallinity, solubility, in vitro dissolution, and in vivo absorption in rats. Scanning electron microscopy images showed distinct differences in the morphologies and dimensions of various celecoxib microcrystals. The particle size of all microcrystals was significantly (P<0.05) reduced relative to plain celecoxib. The DSC and XRD results revealed that MC1 retain drug crystallinity relative to control crystals, MC2, and MC3. All microcrystals showed marked increase in the drug dissolution parameters particularly MC1 that exhibited a prompt drug release and significantly (P<0.05) higher values of % dissolution efficiency as compared to control celecoxib and the other microcrystals. The influence of microcrystals on the in vivo absorption of celecoxib was studied in rats in comparison to plain drug. The results of in vivo absorption study in rats indicated that MC1 significantly improved the rate and extent of celecoxib absorption than plain celecoxib. The mean relative bioavailability of MC1 formulation to plain celecoxib was 157.55±20.18%. In conclusion, microcrystal formulation of celecoxib results not only in an enhancement of dissolution parameters but also improves the bioavailability of celecoxib in rats.

Research paper thumbnail of Custom fractional factorial designs to develop atorvastatin self-nanoemulsifying and nanosuspension delivery systems – enhancement of oral bioavailability

Drug Design, Development and Therapy, 2015

Poor water solubility of a drug is a major challenge in drug delivery research and a main cause f... more Poor water solubility of a drug is a major challenge in drug delivery research and a main cause for limited bioavailability and pharmacokinetic parameters. This work aims to utilize custom fractional factorial design to assess the development of self-nanoemulsifying drug delivery systems (SNEDDS) and solid nanosuspensions (NS) in order to enhance the oral delivery of atorvastatin (ATR). According to the design, 14 experimental runs of ATR SNEDDS were formulated utilizing the highly ATR solubilizing SNEDDS components: oleic acid, Tween 80, and propylene glycol. In addition, 12 runs of NS were formulated by the antisolvent precipitationultrasonication method. Optimized formulations of SNEDDS and solid NS, deduced from the design, were characterized. Optimized SNEDDS formula exhibited mean globule size of 73.5 nm, zeta potential magnitude of-24.1 mV, and 13.5 μs/cm of electrical conductivity. Optimized solid NS formula exhibited mean particle size of 260.3 nm, 7.4 mV of zeta potential, and 93.2% of yield percentage. Transmission electron microscopy showed SNEDDS droplets formula as discrete spheres. The solid NS morphology showed flaky nanoparticles with irregular shapes using scanning electron microscopy. The release behavior of the optimized SNEDDS formula showed 56.78% of cumulative ATR release after 10 minutes. Solid NS formula showed lower rate of release in the first 30 minutes. Bioavailability estimation in Wistar albino rats revealed an augmentation in ATR bioavailability, relative to ATR suspension and the commercial tablets, from optimized ATR SNEDDS and NS formulations by 193.81% and 155.31%, respectively. The findings of this work showed that the optimized nanocarriers enhance the oral delivery and pharmacokinetic profile of ATR.

Research paper thumbnail of In vitro and in vivo evaluation of cubosomes containing 5-fluorouracil for liver targeting

Acta Pharmaceutica Sinica B, 2015

The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic antic... more The objective of this study was to prepare cubosomal nanoparticles containing a hydrophilic anticancer drug 5-fluorouracil (5-FU) for liver targeting. Cubosomal dispersions were prepared by disrupting a cubic gel phase of monoolein and water in the presence of Poloxamer 407 as a stabilizer. Cubosomes loaded with 5-FU were characterized in vitro and in vivo. In vitro, 5-FU-loaded cubosomes entrapped 31.21% drug and revealed nanometer-sized particles with a narrow particle size distribution. In vitro 5-FU release from cubosomes exhibited a phase of rapid release of about half of the entrapped drug during the first hour, followed by a relatively slower drug release as compared to 5-FU solution. In vivo biodistribution experiments indicated that the cubosomal formulation significantly (Po 0.05) increased 5-FU liver concentration, a value approximately 5-fold greater than that observed with a 5-FU solution. However, serum serological results and histopathological findings revealed greater hepatocellular damage in rats treated with cubosomal formulation. These results demonstrate the successful development of cubosomal nanoparticles containing 5-FU for liver targeting. However, further studies are required to evaluate hepatotoxicity and in vivo antitumor activity of lower doses of 5-FU cubosomal formulation in treatment of liver cancer.

Research paper thumbnail of Albendazole-loaded cubosomes interrupt the ERK1/2-HIF-1α-p300/CREB axis in mice intoxicated with diethylnitrosamine: A new paradigm in drug repurposing for the inhibition of hepatocellular carcinoma progression

Biomedicine & Pharmacotherapy

Hepatocellular carcinoma (HCC) is a leading cause of cancer related deaths worldwide. It was sugg... more Hepatocellular carcinoma (HCC) is a leading cause of cancer related deaths worldwide. It was suggested that albendazole (ABZ) is a powerful inhibitor of several carcinoma types. However, the bioavailability of ABZ is very poor. Additionally, the mechanisms underlying the antitumor effects of ABZ may go beyond its tubulin-inhibiting activity. Therefore, we aimed to examine the effects of ABZ suspension (i.p. and p.o.) and ABZ-loaded cubosomes (LC) on the diethylnitrosamine-induced HCC in mice. ABZ-loaded nanoparticles exhibited a mean particle size of 48.17 ± 0.65 nm and entrapped 93.26 ± 2.48% of ABZ. The in vivo absorption study confirmed a two-fold improvement in the relative bioavailability compared with aqueous ABZ suspension. Furthermore, the oral administration of ABZ cubosomal dispersion demonstrated regression of tumor production rates that was comparable with ABZ (i.p.). ABZ relieved oxidative stress, improved liver function, and decreased necroinflammation score. The antiangiogenic activity was evident as ABZ effectively downregulated tissue expression of CD34, mRNA expression of CD309 and VEGF at the protein expression level. Besides, lower levels of MMP-9 and CXCR4 indicated antimetastatic activity. ABZ showed a considerable level of apoptotic activity as indicated by increased mRNA expression level of p53 and the increased Bax/BCL-2 ratio and active caspase-3. Additionally, Ki-67 expression levels were downregulated showing an antiproliferative potential. These protective effects contributed to increasing survival rate of diethylnitrosamine-treated mice. These effects found to be mediated via interrupting ERK1/2-HIF-1α-p300/CREB interactions. Therefore, our findings revealed that disrupting ERK1/2-HIF-1α-p300/CREB interplay might create a novel therapeutic target for the management of HCC.

Research paper thumbnail of Development and characterization of solid lipid nanoparticles loaded with …

International journal of …

This paper describes the preparation of colloidal lipid particles containing magnetite from warm ... more This paper describes the preparation of colloidal lipid particles containing magnetite from warm emulsions. A two step method was used to obtain the nanoparticles: (i) formulation of a transparent phase by heating a O/W emulsion (aqueous surfactant solution melted with a lipid phase, ...

Research paper thumbnail of Preparation and Evaluation of Iron Oxide Nanoparticles for Treatment of Iron Deficiency Anemia

International Journal of Pharmacy and Pharmaceutical Sciences

Objective: The objective of this research was to formulate and evaluate iron oxide nanoparticles ... more Objective: The objective of this research was to formulate and evaluate iron oxide nanoparticles for treatment of iron deficiency anemia (IDA).Methods: Iron oxide nanoparticles were prepared by co-precipitation method and stabilized by coating with folic acid or chitosan. The prepared nanoparticles were characterized in vitro for morphology, particle size, zeta potential, crystallinity and ultraviolet-visible (UV-Vis) absorption. In vivo studies were performed to evaluate the efficacy of the prepared nanoparticles in treating iron-deficient anemic rats compared to the commercial iron product.Results: In vitro results revealed that particle sizes were 65.95±5 nm, 220.2±12 nm and 295.3±19 nm for uncoated iron oxide nanoparticles, folic acid-coated iron oxide nanoparticles and chitosan coated iron oxide nanoparticles, respectively. UV-Vis absorption spectrum and x-ray diffraction (XRD) patterns confirmed that the prepared nanoparticles were iron oxide nanoparticles. In vivo results ind...

Research paper thumbnail of Formulation and clinical evaluation of mucoadhesive buccal films containing hyaluronic acid for treatment of aphthous ulcer

Journal of Drug Delivery Science and Technology

Abstract Hyaluronic acid (HA), a linear polymer of glucuronic acid N acetyl glucosamine disacchar... more Abstract Hyaluronic acid (HA), a linear polymer of glucuronic acid N acetyl glucosamine disaccharide, has tissue healing properties and is used for treatment of oral ulcers. This study aims to develop a controlled release mucoadhesive buccal film containing HA as a novel delivery system to overcome the drawbacks of the fast wash off of mouth rinses and gels used for treatment of aphthous ulcers. HA films are prepared by applying freeze and thaw cross linking technique. A full 21 × 31 × 41 factorial design was applied to study the effect of three independent variables namely polymer type, polymer concentration and the number of freeze/thaw cycles on the selected dependent variables of tensile strength, mucoadhesion and time required to release 50% of HA (T50%). The prepared HA films were evaluated for their physicochemical properties including folding endurance, surface pH, thickness, mucoadhesion properties, tensile strength and in vitro drug release. The optimum formula was evaluated for its clinical efficiency in treatment of patients have aphthous ulcer. The obtained results (good physical properties, mechanical properties (high TS), mucoadhesion properties and controlled release (high t50%)) indicated that an optimum formula for controlled release mucoadhesive buccal film which is aimed to be effective, safe and stable when used in treatment of aphthous ulcers. After clinical study, it was observed that the formulation of the hyaluronic acid resulted in a more potent effect and resistance to the washing effect of saliva and friction from food. The efficacy of hyaluronic acid was greatly affected by formulation which allowing for prolonged contact.

Research paper thumbnail of Formulation and Characterization of Cubosomes Containing REB for Improvement of Oral Absorption of the Drug in Human Volunteers

Journal of Advanced Pharmacy Research

Objective: To prepare rebamipide (REB)-loaded cubosomal nanoparticles to improve the oral bioavai... more Objective: To prepare rebamipide (REB)-loaded cubosomal nanoparticles to improve the oral bioavailability of the drug in human volunteers. Methodology: The poorly water soluble drug REB was incorporated into cubosomal nanoparticles by solvent dilution method. The prepared REB-loaded cubosomes were in vitro characterized for particle size, polydispersity index (PDI), zeta potential, drug crystallinity and in vitro drug release. In vivo absorption of REB-loaded cubosomes was compared with drug powder and commercially available tablets Mucosta ® (Egypt Otsuka Pharmaceutical Company) in healthy human volunteers. Results: In vitro, REB-loaded cubosomes entrapped about 82.44 % drug and revealed nanometer-size ranged from 303.1 ± 4.9 to 444.9 ± 6 nm. In vitro REB release from cubosomes exhibited a phase of rapid and high release of the drug during the first hour followed by a slower and complete drug release over a period of 3 hrs. The results of bioavailability study in healthy human volunteers showed that cubosomes significantly improved the rate and extent of REB absorption. The mean relative bioavailability of the REB loaded cubosomes compared to the drug powder and commercially available tablets (Mucosta ®) was 267.67 % and 166.29 % respectively. Conclusion: The prepared cubosomes significantly improved the In-vivo absorption of REB in comparison with drug powder and commercially available tablets (Mucosta ®).

Research paper thumbnail of In vivo Absorption Study of Solid Dispersion Containing Atorvastatin Calcium in Human Volunteers

Journal of Advanced Pharmacy Research

Objectives: Solid dispersion is a unique and promising approach for improving the oral absorption... more Objectives: Solid dispersion is a unique and promising approach for improving the oral absorption and oral bioavailability of the poorly water soluble drugs. Atorvastatin Calcium (ATV) is an anti-hyper lipidemic agent, It belongs to class II drugs according to the biopharmaceutical classification system (BCS), and undergoes extensive first-pass metabolism after oral absorption exhibiting 12% bioavailability. The Objective of the present study is to investigate the effect of formulating the hydrophobic drug (ATV) in a solid dispersion form on its bioavailability. Methods: ATV solid dispersion (ATV-SD) was prepared by microwave induced fusion method, containing poloxamer188 as a hydrophillic carrier. The resultant ATV-SD was compressed into tablets with other ingredients and was evaluated against pure ATV tablets, in vitro dissolution study was carried out to compare the dissolution profiles of the prepared ATV-SD against the pure form of ATV. In vivo study was conducted using healthy male volunteers (n = 6). A high performance liquid chromatography method was employed to determine the level of drug in human plasma. Results: In vitro dissolution study revealed an enhancement in the dissolution profile of ATV-SD. The study of pharmacokinetics parameters also showed an enhancement after oral administration of ATV-SD tablet when compared with pure ATV tablets, where , the AUC0-60h and Cmax were increased after intake of ATV-SD tablets orally compared with that of pure ATV tablets. Conclusion: All these could be demonstrated that ATV-SD would be prospective means for enhancing higher oral bioavailability of ATV.

Research paper thumbnail of Influence of siRNA Loaded Nanoparticles on the Metastasis and Growth Rate of Cancer Cell Lines

Journal of Advanced Pharmacy Research

Objectives: The aim of this study was to investigate the ability of siRNA-loaded nanoparticles to... more Objectives: The aim of this study was to investigate the ability of siRNA-loaded nanoparticles to control the capability of cisplatin-resistant cell lines to decrease cancer metastasis and cell proliferation rate. Methods: The effect of siRNAloaded NPs on the migratory (metastasis) and proliferation (cell growth rate) activity of cisplatin-resistant cell lines compared to untreated cells was investigated using the wound healing assay and cell growth rate assay, respectively. Results: The results showed that cells were treated with siRNA-loaded nanoparticles after 24 h from starting the scratch, succeeded to cover of 59 ± 12.9, and 30 ± 6.1% only from the wound for cell line Cis 1R and Cis 12R, respectively. On the other hand of the untreated cells that were treated with positive control nanoparticles showed complete healing for the wound within the same period of time. Results of cell proliferation of both cell lines exhibited significantly (P≤ 0.001) lower growth rate after treatment with loaded nanoparticles compared to positive control nanoparticles and untreated cells. Conclusion: The obtained results indicated that siRNA-loaded nanoparticles succeeded to not only reduce metastasis but also decrease cell proliferation rate of cisplatin-resistant cell lines.

Research paper thumbnail of Comparison of drug release from liquid crystalline monoolein dispersions and solid lipid nanoparticles using a flow cytometric technique

Acta pharmaceutica Sinica. B, 2016

Colloidal lipid particles such as solid lipid nanoparticles and liquid crystalline nanoparticles ... more Colloidal lipid particles such as solid lipid nanoparticles and liquid crystalline nanoparticles have great opportunities as drug carriers especially for lipophilic drugs intended for intravenous administration. In order to evaluate drug release from these nanoparticles and determine their behavior after administration, emulsion droplets were used as a lipophilic compartment to which the transfer of a model drug was measured. The detection of the model drug transferred from monoolein cubic particles and trimyristin solid lipid nanoparticles into emulsion droplets was performed using a flow cytometric technique. A higher rate and amount of porphyrin transfer from the solid lipid nanoparticles compared to the monoolein cubic particles was observed. This difference might be attributed to the formation of a highly ordered particle which leads to the expulsion of drug to the surface of the crystalline particle. Furthermore, the sponge-like structure of the monoolein cubic particles decre...

Research paper thumbnail of In Vitro and In Vivo Evaluation of Combined Time and pH- Dependent Oral Colonic Targeted Prednisolone Microspheres

British Journal of Pharmaceutical Research, 2013

Research paper thumbnail of Preparation, Characterization and Therapeutic Activity of Gliclazide Β-Cyclodextrin Inclusion Complex

ABSTRACT The objective of this study was to improve therapeutic activity of gliclazide by improvi... more ABSTRACT The objective of this study was to improve therapeutic activity of gliclazide by improving its aqueous solubility through preparation of inclusion complex between gliclazide and ß-cyclodextrin. Gliclazide ß-cyclodextrin solid complex was prepared with equimolar ratio of both gliclazide and ß-cyclodextrin in presence or absence of water soluble polymers (PVP-K15 and HPMC) using co-evaporation, spray drying and freeze drying techniques. The prepared solid complexes were characterized by DSC, IR, XRD and dissolution testing in comparison with the pure gliclazide powder. The solid complexes prepared by spray drying, freeze drying and co-evaporation in presence of hydrophilic polymers showed a prompt drug release compared to pure gliclazide (P < 0.05). The spry dried complex in presence of PVP-K15 showed the highest drug release after 5 and 90 min and significantly increased the % dissolution efficiency (P < 0.05) compared to the pure drug. Moreover, in vivo assessment of ...

Research paper thumbnail of Optimized zein nanospheres for improved oral bioavailability of atorvastatin

International Journal of Nanomedicine, 2015

Background: This work focuses on the development of atorvastatin utilizing zein, a natural, safe,... more Background: This work focuses on the development of atorvastatin utilizing zein, a natural, safe, and biocompatible polymer, as a nanosized formulation in order to overcome the poor oral bioavailability (12%) of the drug. Methods: Twelve experimental runs of atorvastatin-zein nanosphere formula were formulated by a liquid-liquid phase separation method according to custom fractional factorial design to optimize the formulation variables. The factors studied were: weight % of zein to atorvastatin (X 1), pH (X 2), and stirring time (X 3). Levels for each formulation variable were designed. The selected dependent variables were: mean particle size (Y 1), zeta potential (Y 2), drug loading efficiency (Y 3), drug encapsulation efficiency (Y 4), and yield (Y 5). The optimized formulation was assayed for compatibility using an X-ray diffraction assay. In vitro diffusion of the optimized formulation was carried out. A pharmacokinetic study was also done to compare the plasma profile of the atorvastatin-zein nanosphere formulation versus atorvastatin oral suspension and the commercially available tablet. Results: The optimized atorvastatin-zein formulation had a mean particle size of 183 nm, a loading efficiency of 14.86%, and an encapsulation efficiency of 29.71%. The in vitro dissolution assay displayed an initial burst effect, with a cumulative amount of atorvastatin released of 41.76% and 82.3% after 12 and 48 hours, respectively. In Wistar albino rats, the bioavailability of atorvastatin from the optimized atorvastatin-zein formulation was 3-fold greater than that from the atorvastatin suspension and the commercially available tablet. Conclusion: The atorvastatin-zein nanosphere formulation improved the oral delivery and pharmacokinetic profile of atorvastatin by enhancing its oral bioavailability.

Research paper thumbnail of In Vitro and In Vivo Evaluation of Oxatomide β-Cyclodextrin Inclusion Complex

Journal of Pharmaceutics, 2013

The objective of this study was to evaluate the influence of oxatomide β-cyclodextrin inclusion c... more The objective of this study was to evaluate the influence of oxatomide β-cyclodextrin inclusion complex on the physicochemical properties and bioavailability of the drug. Oxatomide β-cyclodextrin solid complex was prepared with equimolar ratio of both oxatomide and β-cyclodextrin in presence or absence of water soluble polymers using different techniques. The coevaporated complex prepared in presence of PVP-K15 showed a prompt drug release and significantly increased % dissolution efficiency compared to the pure oxatomide. Moreover, the results of bioavailability evaluation of this complex in rabbits compared to commercial drug product indicated a 73.15% increase in the oral bioavailability of oxatomide. In conclusion, inclusion complex of oxatomide with β-cyclodextrin prepared by coevaporation in presence of PVP-K15 not only results in an enhancement of the oxatomide dissolution rate but also improves the bioavailability of oxatomide.

Research paper thumbnail of Formulation and evaluation of mastic gum as a compression coat for colonic delivery of 5-flurouracil

International Journal of Drug Delivery, 2011

Mastic gum has been reported to possess considerable anti-tumor activity against human colorectal... more Mastic gum has been reported to possess considerable anti-tumor activity against human colorectal cancer. The purpose of this work was to evaluate mastic gum in formulation of colon-specific 5-flurouracil delivery system for effective treatment of ...

Research paper thumbnail of In vitrocytotoxicity and bioavailability of solid lipid nanoparticles containing tamoxifen citrate

Pharmaceutical Development and Technology, 2014

The objective of this study was to evaluate the influence of solid lipid nanoparticles (SLN) load... more The objective of this study was to evaluate the influence of solid lipid nanoparticles (SLN) loaded with the poorly water-soluble drug tamoxifen citrate (TC) on the in vitro antitumor activity and bioavailability of the drug. TC-loaded SLN were prepared by solvent injection method using glycerol monostearate (GMS) or stearic acid (SA) as lipid matrix. Poloxamer 188 or tween 80 were used as stabilizers. TC-loaded SLN (F3 and F4) prepared using GMS and stabilized by poloxamer 188 showed highest entrapment efficiency % (86.07 ± 1.74 and 90.40 ± 1.22%) and reasonable mean particle sizes (130.40 ± 9.45 and 243.80 ± 12.33 nm), respectively. The in vitro release of TC from F3 and F4 exhibited an initial burst effect followed by a sustained drug release. In vitro cytotoxicity of F3 against human breast cancer cell line MCF-7 showed comparable antitumor activity to free drug. Moreover, the results of bioavailability evaluation of TC-loaded SLN in rats compared to free TC indicated that 160.61% increase in the oral bioavailability of TC. The obtained results suggest that incorporation of the poorly water-soluble drug TC in SLN preserves the in vitro antitumor activity and significantly enhance oral bioavailability of TC in rats.

Research paper thumbnail of Guar gum and hydroxy propyl methylcellulose compressed coated tablets for colonic drug delivery: in vitro and in vivo evaluation in healthy human volunteers

Drug Discoveries & Therapeutics, 2011

The objectives of the present study are to evaluate guar gum in combination with hydroxy propyl m... more The objectives of the present study are to evaluate guar gum in combination with hydroxy propyl methylcellulose (HPMC) as compression coat for colonic delivery of prednisolone as well as improving the mechanical properties of the compressed coated tablets. The core tablets containing 5 mg prednisolone were compression coated with 125 mg of coating materials consisted of guar gum alone or mixtures of guar gum in combination with different ratios of HPMC. The compressed coated tablets were evaluated for their mechanical properties, in vitro drug release and in vivo performance in human volunteers. The compressed coated tablets with coats containing HPMC exhibited acceptable mechanical properties. In vitro drug release studies in pH 7.4 phosphate-buffered saline medium containing 2% (w/v) rat caecal content have shown that increase in concentration of HPMC in the prepared coats from 10% to 20% resulted in an increase in the release rate. However, further increase in HPMC concentration to constitute 30% caused a reduction in the release rate. Based on the drug release results, tablets coated with coat consisted of 80% guar gum and 20% HPMC were selected for in vivo evaluation. In vivo gamma scintigraphic study on human volunteers using technetium-99m-diethylenetriamine pentaacetic acid as a tracer was performed. The results showed that tablets remained intact in stomach and small intestine, however partial and complete release of the tracer occurred in the colon. In conclusion, guar gum in combination with HPMC would be successfully used as a carrier for drug delivery to the colon.

Research paper thumbnail of Formulation, Characterization, and Clinical Evaluation of Microemulsion Containing Clotrimazole for Topical Delivery

AAPS PharmSciTech, 2011

The objective of the present study was to formulate and evaluate microemulsion systems for topica... more The objective of the present study was to formulate and evaluate microemulsion systems for topical delivery of clotrimazole (CTM). The solubility of CTM in various oils was determined to select the oil phase of the microemulsion systems. Pseudoternary phase diagrams were constructed to identify the area of microemulsion existence. Five CTM microemulsion formulations (M1-M5) were prepared and evaluated for their thermodynamic stability, pH, refractive index, droplet size, viscosity, and in vitro release across cellulose membrane. Among the prepared microemulsion formulations, M3 (lemon oil/ Tween 80/n-butanol/water) and M4 (isopropyl myristate/Tween 80/n-butanol/water) microemulsion systems were found to be promising according to their physical properties and CTM cumulative percentage release. Gel form of M3 and M4 were prepared using 1% Carbopol 940 as the hydrogel matrix. Both formulations were evaluated in the liquid and gel forms for drug retention in the skin in comparison to the marketed CTM topical cream and their stability examined after storage at 40°C for 6 months. Microemulsion formulations achieved significantly higher skin retention for CTM over the CTM cream. Stability studies showed that M4 preparations were more stable than M3. The in vitro antifungal activity of M4 against Candida albicans was higher than that of the conventional cream. Moreover, clinical evaluation proved the efficacy and tolerability of this preparation in the treatment of various topical fungal infections.

Research paper thumbnail of In Vitro and In Vivo Evaluation of Proniosomes Containing Celecoxib for Oral Administration

AAPS PharmSciTech, 2010

The objectives of this research were to prepare celecoxib proniosomes and evaluate the influence ... more The objectives of this research were to prepare celecoxib proniosomes and evaluate the influence of proniosomal formulation on the oral bioavailability of the drug in human volunteers. A new proniosomal delivery system for a poorly water-soluble drug such as celecoxib was developed and subjected to in vitro and in vivo studies. Proniosomes were prepared by sequential spraying method, which consisted of cholesterol, span 60, and dicetyl phosphate in a molar ratio of 1:1: 0.1, respectively. The average entrapment percent of celecoxib proniosome-derived niosomes was about 95%. The prepared proniosomes showed marked enhancement in the dissolution of celecoxib as compared to pure drug powder. The bioavailability of 200 mg single dose of both celecoxib proniosomal formulation and a conventional marketed celecoxib capsule was studied in human volunteers. The obtained results show that the proniosomal formulation significantly improved the extent of celecoxib absorption than conventional capsule. The mean relative bioavailability of the proniosomal formulation to the conventional capsule was 172.06±0.14%. The mean T max for celecoxib was prolonged when given as proniosomal capsule. There was no significant difference between the values of K el and t 1/2 for both celecoxib preparations. In conclusion, the proniosomal oral delivery system of celecoxib with improved bioavailability was established.

Research paper thumbnail of Influence of Microcrystal Formulation on In Vivo Absorption of Celecoxib in Rats

AAPS PharmSciTech, 2013

The objective of this study was to prepare celecoxib microcrystals using different stabilizers in... more The objective of this study was to prepare celecoxib microcrystals using different stabilizers in order to evaluate the influence of microcrystal formulation on the in vitro dissolution rate and in vivo absorption after oral administration of celecoxib in rats. Three celecoxib microcrystals (MC1, MC2, and MC3) were prepared using solvent change method. Microcrystals were evaluated for morphology, particle size, crystallinity, solubility, in vitro dissolution, and in vivo absorption in rats. Scanning electron microscopy images showed distinct differences in the morphologies and dimensions of various celecoxib microcrystals. The particle size of all microcrystals was significantly (P<0.05) reduced relative to plain celecoxib. The DSC and XRD results revealed that MC1 retain drug crystallinity relative to control crystals, MC2, and MC3. All microcrystals showed marked increase in the drug dissolution parameters particularly MC1 that exhibited a prompt drug release and significantly (P<0.05) higher values of % dissolution efficiency as compared to control celecoxib and the other microcrystals. The influence of microcrystals on the in vivo absorption of celecoxib was studied in rats in comparison to plain drug. The results of in vivo absorption study in rats indicated that MC1 significantly improved the rate and extent of celecoxib absorption than plain celecoxib. The mean relative bioavailability of MC1 formulation to plain celecoxib was 157.55±20.18%. In conclusion, microcrystal formulation of celecoxib results not only in an enhancement of dissolution parameters but also improves the bioavailability of celecoxib in rats.