Majid Darabi - Academia.edu (original) (raw)

Papers by Majid Darabi

Research paper thumbnail of Spray freeze drying to solidify Nanosuspension of Cefixime into inhalable microparticles

DARU Journal of Pharmaceutical Sciences, 2022

Purpose Spray-freeze drying (SFD) incorporating diverse carbohydrates and leucine was employed to... more Purpose Spray-freeze drying (SFD) incorporating diverse carbohydrates and leucine was employed to obtain dried nanosuspension of cefixime with improved dissolution profile, good dispersibility, and excellent inhalation performance. Methods Nanoprecipitation was utilized to prepare nanoparticles (NPs). Nanosuspensions of cefixime were solidified via SFD to access inhalable microparticles. The aerosolization efficiencies were evaluated through twin stage impinger (TSI). Laser light scattering and scanning electron microscopy (SEM) provided assistance to determine the particle size/size distribution and morphology, respectively. Amorphous/ crystalline states of materials were examined via differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Release profiles of candidate preparations were evaluated. Results The fine particle fraction (FPF) ranged from 18.96 ± 0.76 to 79.28 ± 0.45%. The highest value resulted from trehalose with NP/carrier ratio of 1:1 and leucine 20%. The particle size varied from 5.24 ± 0.97 to 10.17 ± 1.01 μm. The most and the least size distribution were achieved in mannitol and trehalose containing formulations, respectively. The majority of samples demonstrated ideally spherical morphology with diverse degrees of porosity and without needle-shaped structure. Percentages of release in F 7 and F 8 were 89.33 ± 0.88% and 93.54 ± 1.02%, respectively, via first 10 min. Conclusion SFD of nanosuspensions can be established as a platform for the pulmonary delivery of poorly water-soluble molecules of cefixime. Trehalose and raffinose with a lower ratio of NP to the carrier and higher level of leucine could be introduced as favorable formulations for further respiratory delivery of cefixime. Graphical abstract

Research paper thumbnail of Preparation, characterization and optimization of sildenafil citrate loaded PLGA nanoparticles by statistical factorial design

DARU Journal of Pharmaceutical Sciences, 2013

Background and the aim of the studyThe objective of the present study was to formulate and optimi... more Background and the aim of the studyThe objective of the present study was to formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co-glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The relationship between design factors and experimental data was evaluated using response surface methodology.MethodA Box-Behnken design was made considering the mass ratio of drug to polymer (D/P), the volumetric proportion of the water to oil phase (W/O) and the concentration of polyvinyl alcohol (PVA) as the independent agents. PLGA-NPs were successfully prepared and the size (nm), entrapment efficiency (EE), drug loading (DL) and cumulative release of drug from NPs post 1 and 8 hrs were assessed as the responses.ResultsThe NPs were prepared in a spherical shape and the sizes range of 240 to 316 nm. The polydispersity index of size was lower than 0.5 and the EE (%) and DL (%) varied between 14-62% and 2-6%, respectively. The optimized formulation wit...

Research paper thumbnail of Triarylpyrazole Derivatives as Potent Cytotoxic Agents; Synthesis and Bioactivity Evaluation “Pyrazole Derivatives as Anticancer Agent”

Drug Research

Background During the last recent years, several anti-cancer agents were introduced for the treat... more Background During the last recent years, several anti-cancer agents were introduced for the treatment of diverse kinds of cancer. Despite their potential in the treatment of cancer, drug resistance and adverse toxicity such as peripheral neuropathy are some of the negative criteria of anti-cancer agents and for this reason, the design and synthesis of new anti-cancer agents are important. Objective Design, synthesis, and anticancer activity evaluation of some pyrazole derivatives. Methods A series of Target compounds were prepared using multistep synthesis. Their cytotoxic activity against three different human cancer cell lines namely human colon carcinoma cells (HT-29), epithelial carcinoma cells (U-87MG), pancreatic cancerous cells (Panc-1) as well as AGO1522 normal cell line using in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was investigated. Results 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole and 1,3-Diaryl-5-(3,4,5-trimet...

Research paper thumbnail of Human Serum Albumin, a Suitable Candidate to Stabilize Freeze-Dried IgG in Combination with Trehalose: Central Composite Design

Research paper thumbnail of Application of disaccharides alone and in combination, for the improvement of stability and particle properties of spray-freeze dried IgG

Pharmaceutical Development and Technology

Research paper thumbnail of Optimization of Stable IgG Formulation Containing Amino Acids and Trehalose During Freeze-Drying and After Storage: a Central Composite Design

Research paper thumbnail of Preparation and physicochemical evaluation of a new tacrolimus tablet formulation for sublingual administration

Drug Development and Industrial Pharmacy, Sep 30, 2011

The aim of this study was to develop a new fast-disintegrating tablet formulation containing 1 mg... more The aim of this study was to develop a new fast-disintegrating tablet formulation containing 1 mg tacrolimus for sublingual application. First, solid dispersions containing tacrolimus (2.5%, 5% and 10% w/w) incorporated in Ac-Di-Sol ® and carriers (inulin 1.8 kDa and 4 kDa, and polyvinylpyrrolidone (PVP) K30) were prepared by freeze drying. Subsequently, a tablet formulation composed of a mixture of the solid dispersions, Ac-Di-Sol ® , mannitol, Avicel ® PH-101 and sodium stearyl fumarate was optimized concerning drug load in the solid dispersions and the type of carrier. Tablet weight was kept constant at 75 mg by adjusting the amount of Avicel ® PH-101. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) results indicated the absence of the drug in the crystalline state, which was confirmed by the scanning electron microscopy (SEM). These results suggest that tacrolimus incorporated in all of the solid dispersions was fully amorphous. Dissolution of the tablets containing solid dispersions with a low drug load highly depends on the type of carrier and increased in the order: PVP K30 < inulin 4 kDa < inulin 1.8 kDa. Solid dispersions with a drug load of 10% w/w incorporated in the carriers yielded optimal formulations. In addition, the physicochemical characteristics and the dissolution behavior of the tablet formulation containing inulin 1.8 kDabased solid dispersions with a drug load of 10% w/w did not change after storage at 20°C/45%RH for 6 months indicating excellent storage stability.

Research paper thumbnail of Influence of formulation variables and inhalation device on the deposition profiles of cromolyn sodium dry powder aerosols

Dry powder inhalers (DPIs) have attained considerable attention due to their propellant-free form... more Dry powder inhalers (DPIs) have attained considerable attention due to their propellant-free formulations and the patient's inherent coordination with actuation. Generally, DPI formulations consist of a micronized drug alone or mixed with carrier particles. This study was carried out to investigate the effects of carrier particle size and weight fraction on aerosolisation behaviour of cromolyn sodium (CS). Pharmatose® 450M and Pharmatose® 325M, two commercial α-lactose monohydrate with different particle sizes, were blended in two different fractions (30 and 50% w/w) with CS. A low resistance device (Spinhaler®) and a medium resistance device (Cyclohaler®), were used to evaluate the effect of inhaler design on the deposition profiles of CS. The in vitro deposition of the formulations was determined using a twin stage impinger (TSI). Fine particle dose, fine particle fraction and emitted dose of the drug were depended to both formulation and inhalation devices. Fine particle fractions of the drug aerosolised from the formulations ranged from 9.35 up to 36.45%. The highest fine particle fraction was produced by formulation containing 50% Pharmatose® 450M as carrier. Cyclohaler® showed higher efficiency in aerosolisation of CS compared to Spinhaler®.

Research paper thumbnail of Determination of Rofecoxib in Serum with Pre-column Derivatization and Fluorescence Detection

International Journal of Pharmacology, 2005

Research paper thumbnail of DARU Journal of Pharmaceutical Sciences

DARU, 2002

Abstract: This study was designed to investigate the relative role of sweetness and comparative e... more Abstract: This study was designed to investigate the relative role of sweetness and comparative effects of different taste sensation of the non-caloric sweetener, aspartame on pain and its interaction with MK-80] as a non-selective MMDA antagonist by formalin-test in mice. The formalin-test was chosen because it measures the response to a long-lasting nociceptive stimulus and closely resembles to the clinical pain. Morphine induced a dose dependent antinociception in the early and late phases of formalin test. Twelve days ...

Research paper thumbnail of Effects of combined therapy with thalidomide and glucantime on leishmaniasis induced by Leishmania major in BALB/c mice

The Korean journal of parasitology, 2006

For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with g... more For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with glucantime. Groups of mice were challenged with 510(3) metacyclic promastigotes of L. major subcutaneously. A week after the challenge, drug treatment was started and continued for 12 days. Thalidomide was orally administrated 30 mg/kg/day and glucantime was administrated intraperitoneally (200 mg/kg/day). It was shown that the combined therapy is more effective than single therapies with each one of the drugs since the foot pad swelling in the group of mice received thalidomide and glucantime was significantly decreased (0.9 +/- 0.2 mm) compared to mice treated with either glucantime, thalidomide, or carrier alone (1.2 +/- 0.25, 1.4 +/- 0.3, and 1.7 +/- 0.27 mm, respectively). Cytokine study showed that the effect of thalidomide was not dependent on IL-12; however, it up-regulated IFN-gamma and down-regulated IL-10 production. Conclusively, thalidomide seems promising as a conjunctive th...

Research paper thumbnail of Effect of formulation ingredients on the physical characteristics of salmeterol xinafoate microparticles tailored by spray freeze drying

ABSTRACT Series of microparticles containing salmeterol xinafoate (SX) as active pharmaceutical i... more ABSTRACT Series of microparticles containing salmeterol xinafoate (SX) as active pharmaceutical ingredient (API) and lactose, mannitol or trehalose as a bulking agents were prepared using spray freeze drying (SFD) technique and the effects of sugar type and presence of hydroxy propyl beta cyclodextrin (HPβCD) on the physical properties of powders were evaluated. Precipitation of salmeterol in the presence of lactose and mannitol resulted in the formation of irregular shapes of microparticles with broad size distributions. However application of trehalose resulted in the formation of porous particles with spherical morphology. Addition of cyclodextrin in the formulations was generally helpful for formation of porous and spherical particles with narrow size distribution with a mean size of 10–30 μm. Dissolution of SX from processed particles was substantially higher (∼90% drug release in 30 min) than that of unprocessed drug and physical mixture of drug and cyclodextrin (∼22% drug release in 30 min). This study showed that, processing of SX by SFD technique could be a constructive approach to the production of various forms of drug and drastic changes in the physical characteristics of microparticles could be achieved by changing the composition of bulking agent and cyclodextrin.

Research paper thumbnail of Preparation, characterization and optimization of sildenafil citrate loaded PLGA nanoparticles by statistical factorial design

DARU Journal of Pharmaceutical Sciences, 2013

Background and the aim of the study: The objective of the present study was to formulate and opti... more Background and the aim of the study: The objective of the present study was to formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co-glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The relationship between design factors and experimental data was evaluated using response surface methodology.

Research paper thumbnail of Loading hydrophilic drug in solid lipid media as nanoparticles: Statistical modeling of entrapment efficiency and particle size

International Journal of Pharmaceutics, 2012

Solid lipid nanoparticle (SLN) is a very well tolerated carrier systems for dermal application du... more Solid lipid nanoparticle (SLN) is a very well tolerated carrier systems for dermal application due to the employment physiological and/or biodegradable lipids. The effects of five factors, two categorical and three quantitative factors, were studied on the mean diameter and entrapment efficiency of the produced SLNs using response surface method (RSM), D-optimal design. Two methods of microemulsion and solvent diffusion and two types of lipid, cetyl palmitate and stearic acid, were examined comparatively. The quantitative variables were studied in three levels; amount of original Paromomycin (60, 90 and 120 mg), fraction of surfactant (0.5, 0.75 and 1 w/v %) and drug to lipid ratio (2, 4 and 6). Mean particle size and entrapment efficiency of the loaded Paromomycin were modeled statistically and the optimal condition was determined to approach to the maximum entrapment efficiency. The drug release profile of the optimal formulated material was examined in aqueous media and 64% of the Paromomycin loaded in SLNs was gradually released during 24 h, which reveals efficient prolonged release of the drug.

Research paper thumbnail of Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

International Journal of Nanomedicine, 2010

This study concerns the supercritical antisolvent process which allows single-step production of ... more This study concerns the supercritical antisolvent process which allows single-step production of 5-fluorouracil (5-FU) nanoparticles. This process enhances the physical characteristics of 5-FU in order to deliver it directly to the respiratory tract. Several mixtures of methanol with dichloromethane, acetone, or ethanol were used for particle preparation, and their effects on the physical characteristics of the final products were studied. The conditions of the experiment included pressures of 100 and 150 bar, temperature of 40°C, and a flow rate of 1 mL/min. The particles were characterized physicochemically before and after the process for their morphology and crystallinity. In spite of differences in size, the particles were not very different regarding their morphology. The resulting particles were of a regular shape, partly spherical, and appeared to have a smooth surface, whereas the mechanically milled particles showed less uniformity, had surface irregularities and a high particle size distribution, and seemed aggregated. Particles of 5-FU precipitated from methanol-dichloromethane 50:50 had a mean particle size of 248 nm. In order to evaluate the aerodynamic behavior of the nanoparticles, six 5-FU dry powder formulations containing mixtures of coarse and fine lactose of different percentages were prepared. Deposition of 5-FU was measured using a twin-stage liquid impinger and analyzed using a validated high pressure liquid chromatography method. Addition of fine lactose improved the aerodynamic performance of the drug, as determined by the fine particle fraction.

Research paper thumbnail of Three phase liquid phase microextraction of phenylacetic acid and phenylpropionic acid from biological fluids

Journal of Chromatography B, 2007

Three phase liquid phase microextraction (three phase LPME) technique coupled with HPLC-UV has be... more Three phase liquid phase microextraction (three phase LPME) technique coupled with HPLC-UV has been applied as a sensitive and efficient sample preparation method to determine phenylacetic acid (PAA) as a biomarker of depressive disorders and phenylpropionic acid (PPA) in biological fluids. The compounds were extracted from 3.0 ml aqueous solution with the adjustment of pH at a fixed value in the range of 2.0-3.5 (donor solution) into an organic phase (1-hexanol) layered on the surface of the donor solution and finally back-extracted into 4.0 l of the acceptor microdrop (pH 11.1) located at the end of the microsyringe needle. After a prescribed back-extraction time, the acceptor microdrop was withdrawn into the microsyringe and then directly injected into the HPLC system. In order to achieve maximum extraction efficiency, different parameters affecting the extraction conditions were optimized. At the optimum conditions (donor solution: 2.3 M Na 2 SO 4 , pH 2.0-3.5; organic membrane: 95 l of 1-hexanol; acceptor solution: 4.0 l of 0.1 M NH 3 /NH 4 + with pH 11.1; donor solution temperature: 45-50 • C; extraction time: 20 min and back-extraction time: 12 min), up to 110-fold enrichment factor was obtained. The calibration curve for these analytes was linear in the range of 1-5000 g/l with r 2 > 0.998. The intraday and interday RSD% were below 6.5% and the limits of detection (LODs) for both analytes were 0.2 g/l (based on S/N = 3). The proposed technique is a low cost, simple and sensitive method with highly clean-up effect. Finally, this technique was successfully utilized for the detection of target analytes in human urine, serum and plasma.

Research paper thumbnail of Effects of combined therapy with thalidomide and glucantime on leishmaniasis induced by Leishmania major in BALB/c mice

The Korean journal of …, 2006

For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with g... more For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with glucantime. Groups of mice were challenged with 5× 10 3 metacyclic promastigotes of L. major subcutaneously. A week after the challenge, drug treatment was ...

Research paper thumbnail of Effect of formulation ingredients on the physical characteristics of salmeterol xinafoate microparticles tailored by spray freeze drying

Advanced Powder Technology, 2013

ABSTRACT Series of microparticles containing salmeterol xinafoate (SX) as active pharmaceutical i... more ABSTRACT Series of microparticles containing salmeterol xinafoate (SX) as active pharmaceutical ingredient (API) and lactose, mannitol or trehalose as a bulking agents were prepared using spray freeze drying (SFD) technique and the effects of sugar type and presence of hydroxy propyl beta cyclodextrin (HPβCD) on the physical properties of powders were evaluated. Precipitation of salmeterol in the presence of lactose and mannitol resulted in the formation of irregular shapes of microparticles with broad size distributions. However application of trehalose resulted in the formation of porous particles with spherical morphology. Addition of cyclodextrin in the formulations was generally helpful for formation of porous and spherical particles with narrow size distribution with a mean size of 10–30 μm. Dissolution of SX from processed particles was substantially higher (∼90% drug release in 30 min) than that of unprocessed drug and physical mixture of drug and cyclodextrin (∼22% drug release in 30 min). This study showed that, processing of SX by SFD technique could be a constructive approach to the production of various forms of drug and drastic changes in the physical characteristics of microparticles could be achieved by changing the composition of bulking agent and cyclodextrin.

Research paper thumbnail of Spray freeze drying to solidify Nanosuspension of Cefixime into inhalable microparticles

DARU Journal of Pharmaceutical Sciences, 2022

Purpose Spray-freeze drying (SFD) incorporating diverse carbohydrates and leucine was employed to... more Purpose Spray-freeze drying (SFD) incorporating diverse carbohydrates and leucine was employed to obtain dried nanosuspension of cefixime with improved dissolution profile, good dispersibility, and excellent inhalation performance. Methods Nanoprecipitation was utilized to prepare nanoparticles (NPs). Nanosuspensions of cefixime were solidified via SFD to access inhalable microparticles. The aerosolization efficiencies were evaluated through twin stage impinger (TSI). Laser light scattering and scanning electron microscopy (SEM) provided assistance to determine the particle size/size distribution and morphology, respectively. Amorphous/ crystalline states of materials were examined via differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Release profiles of candidate preparations were evaluated. Results The fine particle fraction (FPF) ranged from 18.96 ± 0.76 to 79.28 ± 0.45%. The highest value resulted from trehalose with NP/carrier ratio of 1:1 and leucine 20%. The particle size varied from 5.24 ± 0.97 to 10.17 ± 1.01 μm. The most and the least size distribution were achieved in mannitol and trehalose containing formulations, respectively. The majority of samples demonstrated ideally spherical morphology with diverse degrees of porosity and without needle-shaped structure. Percentages of release in F 7 and F 8 were 89.33 ± 0.88% and 93.54 ± 1.02%, respectively, via first 10 min. Conclusion SFD of nanosuspensions can be established as a platform for the pulmonary delivery of poorly water-soluble molecules of cefixime. Trehalose and raffinose with a lower ratio of NP to the carrier and higher level of leucine could be introduced as favorable formulations for further respiratory delivery of cefixime. Graphical abstract

Research paper thumbnail of Preparation, characterization and optimization of sildenafil citrate loaded PLGA nanoparticles by statistical factorial design

DARU Journal of Pharmaceutical Sciences, 2013

Background and the aim of the studyThe objective of the present study was to formulate and optimi... more Background and the aim of the studyThe objective of the present study was to formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co-glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The relationship between design factors and experimental data was evaluated using response surface methodology.MethodA Box-Behnken design was made considering the mass ratio of drug to polymer (D/P), the volumetric proportion of the water to oil phase (W/O) and the concentration of polyvinyl alcohol (PVA) as the independent agents. PLGA-NPs were successfully prepared and the size (nm), entrapment efficiency (EE), drug loading (DL) and cumulative release of drug from NPs post 1 and 8 hrs were assessed as the responses.ResultsThe NPs were prepared in a spherical shape and the sizes range of 240 to 316 nm. The polydispersity index of size was lower than 0.5 and the EE (%) and DL (%) varied between 14-62% and 2-6%, respectively. The optimized formulation wit...

Research paper thumbnail of Triarylpyrazole Derivatives as Potent Cytotoxic Agents; Synthesis and Bioactivity Evaluation “Pyrazole Derivatives as Anticancer Agent”

Drug Research

Background During the last recent years, several anti-cancer agents were introduced for the treat... more Background During the last recent years, several anti-cancer agents were introduced for the treatment of diverse kinds of cancer. Despite their potential in the treatment of cancer, drug resistance and adverse toxicity such as peripheral neuropathy are some of the negative criteria of anti-cancer agents and for this reason, the design and synthesis of new anti-cancer agents are important. Objective Design, synthesis, and anticancer activity evaluation of some pyrazole derivatives. Methods A series of Target compounds were prepared using multistep synthesis. Their cytotoxic activity against three different human cancer cell lines namely human colon carcinoma cells (HT-29), epithelial carcinoma cells (U-87MG), pancreatic cancerous cells (Panc-1) as well as AGO1522 normal cell line using in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was investigated. Results 1,3-Diaryl-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole and 1,3-Diaryl-5-(3,4,5-trimet...

Research paper thumbnail of Human Serum Albumin, a Suitable Candidate to Stabilize Freeze-Dried IgG in Combination with Trehalose: Central Composite Design

Research paper thumbnail of Application of disaccharides alone and in combination, for the improvement of stability and particle properties of spray-freeze dried IgG

Pharmaceutical Development and Technology

Research paper thumbnail of Optimization of Stable IgG Formulation Containing Amino Acids and Trehalose During Freeze-Drying and After Storage: a Central Composite Design

Research paper thumbnail of Preparation and physicochemical evaluation of a new tacrolimus tablet formulation for sublingual administration

Drug Development and Industrial Pharmacy, Sep 30, 2011

The aim of this study was to develop a new fast-disintegrating tablet formulation containing 1 mg... more The aim of this study was to develop a new fast-disintegrating tablet formulation containing 1 mg tacrolimus for sublingual application. First, solid dispersions containing tacrolimus (2.5%, 5% and 10% w/w) incorporated in Ac-Di-Sol ® and carriers (inulin 1.8 kDa and 4 kDa, and polyvinylpyrrolidone (PVP) K30) were prepared by freeze drying. Subsequently, a tablet formulation composed of a mixture of the solid dispersions, Ac-Di-Sol ® , mannitol, Avicel ® PH-101 and sodium stearyl fumarate was optimized concerning drug load in the solid dispersions and the type of carrier. Tablet weight was kept constant at 75 mg by adjusting the amount of Avicel ® PH-101. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) results indicated the absence of the drug in the crystalline state, which was confirmed by the scanning electron microscopy (SEM). These results suggest that tacrolimus incorporated in all of the solid dispersions was fully amorphous. Dissolution of the tablets containing solid dispersions with a low drug load highly depends on the type of carrier and increased in the order: PVP K30 < inulin 4 kDa < inulin 1.8 kDa. Solid dispersions with a drug load of 10% w/w incorporated in the carriers yielded optimal formulations. In addition, the physicochemical characteristics and the dissolution behavior of the tablet formulation containing inulin 1.8 kDabased solid dispersions with a drug load of 10% w/w did not change after storage at 20°C/45%RH for 6 months indicating excellent storage stability.

Research paper thumbnail of Influence of formulation variables and inhalation device on the deposition profiles of cromolyn sodium dry powder aerosols

Dry powder inhalers (DPIs) have attained considerable attention due to their propellant-free form... more Dry powder inhalers (DPIs) have attained considerable attention due to their propellant-free formulations and the patient's inherent coordination with actuation. Generally, DPI formulations consist of a micronized drug alone or mixed with carrier particles. This study was carried out to investigate the effects of carrier particle size and weight fraction on aerosolisation behaviour of cromolyn sodium (CS). Pharmatose® 450M and Pharmatose® 325M, two commercial α-lactose monohydrate with different particle sizes, were blended in two different fractions (30 and 50% w/w) with CS. A low resistance device (Spinhaler®) and a medium resistance device (Cyclohaler®), were used to evaluate the effect of inhaler design on the deposition profiles of CS. The in vitro deposition of the formulations was determined using a twin stage impinger (TSI). Fine particle dose, fine particle fraction and emitted dose of the drug were depended to both formulation and inhalation devices. Fine particle fractions of the drug aerosolised from the formulations ranged from 9.35 up to 36.45%. The highest fine particle fraction was produced by formulation containing 50% Pharmatose® 450M as carrier. Cyclohaler® showed higher efficiency in aerosolisation of CS compared to Spinhaler®.

Research paper thumbnail of Determination of Rofecoxib in Serum with Pre-column Derivatization and Fluorescence Detection

International Journal of Pharmacology, 2005

Research paper thumbnail of DARU Journal of Pharmaceutical Sciences

DARU, 2002

Abstract: This study was designed to investigate the relative role of sweetness and comparative e... more Abstract: This study was designed to investigate the relative role of sweetness and comparative effects of different taste sensation of the non-caloric sweetener, aspartame on pain and its interaction with MK-80] as a non-selective MMDA antagonist by formalin-test in mice. The formalin-test was chosen because it measures the response to a long-lasting nociceptive stimulus and closely resembles to the clinical pain. Morphine induced a dose dependent antinociception in the early and late phases of formalin test. Twelve days ...

Research paper thumbnail of Effects of combined therapy with thalidomide and glucantime on leishmaniasis induced by Leishmania major in BALB/c mice

The Korean journal of parasitology, 2006

For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with g... more For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with glucantime. Groups of mice were challenged with 510(3) metacyclic promastigotes of L. major subcutaneously. A week after the challenge, drug treatment was started and continued for 12 days. Thalidomide was orally administrated 30 mg/kg/day and glucantime was administrated intraperitoneally (200 mg/kg/day). It was shown that the combined therapy is more effective than single therapies with each one of the drugs since the foot pad swelling in the group of mice received thalidomide and glucantime was significantly decreased (0.9 +/- 0.2 mm) compared to mice treated with either glucantime, thalidomide, or carrier alone (1.2 +/- 0.25, 1.4 +/- 0.3, and 1.7 +/- 0.27 mm, respectively). Cytokine study showed that the effect of thalidomide was not dependent on IL-12; however, it up-regulated IFN-gamma and down-regulated IL-10 production. Conclusively, thalidomide seems promising as a conjunctive th...

Research paper thumbnail of Effect of formulation ingredients on the physical characteristics of salmeterol xinafoate microparticles tailored by spray freeze drying

ABSTRACT Series of microparticles containing salmeterol xinafoate (SX) as active pharmaceutical i... more ABSTRACT Series of microparticles containing salmeterol xinafoate (SX) as active pharmaceutical ingredient (API) and lactose, mannitol or trehalose as a bulking agents were prepared using spray freeze drying (SFD) technique and the effects of sugar type and presence of hydroxy propyl beta cyclodextrin (HPβCD) on the physical properties of powders were evaluated. Precipitation of salmeterol in the presence of lactose and mannitol resulted in the formation of irregular shapes of microparticles with broad size distributions. However application of trehalose resulted in the formation of porous particles with spherical morphology. Addition of cyclodextrin in the formulations was generally helpful for formation of porous and spherical particles with narrow size distribution with a mean size of 10–30 μm. Dissolution of SX from processed particles was substantially higher (∼90% drug release in 30 min) than that of unprocessed drug and physical mixture of drug and cyclodextrin (∼22% drug release in 30 min). This study showed that, processing of SX by SFD technique could be a constructive approach to the production of various forms of drug and drastic changes in the physical characteristics of microparticles could be achieved by changing the composition of bulking agent and cyclodextrin.

Research paper thumbnail of Preparation, characterization and optimization of sildenafil citrate loaded PLGA nanoparticles by statistical factorial design

DARU Journal of Pharmaceutical Sciences, 2013

Background and the aim of the study: The objective of the present study was to formulate and opti... more Background and the aim of the study: The objective of the present study was to formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co-glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The relationship between design factors and experimental data was evaluated using response surface methodology.

Research paper thumbnail of Loading hydrophilic drug in solid lipid media as nanoparticles: Statistical modeling of entrapment efficiency and particle size

International Journal of Pharmaceutics, 2012

Solid lipid nanoparticle (SLN) is a very well tolerated carrier systems for dermal application du... more Solid lipid nanoparticle (SLN) is a very well tolerated carrier systems for dermal application due to the employment physiological and/or biodegradable lipids. The effects of five factors, two categorical and three quantitative factors, were studied on the mean diameter and entrapment efficiency of the produced SLNs using response surface method (RSM), D-optimal design. Two methods of microemulsion and solvent diffusion and two types of lipid, cetyl palmitate and stearic acid, were examined comparatively. The quantitative variables were studied in three levels; amount of original Paromomycin (60, 90 and 120 mg), fraction of surfactant (0.5, 0.75 and 1 w/v %) and drug to lipid ratio (2, 4 and 6). Mean particle size and entrapment efficiency of the loaded Paromomycin were modeled statistically and the optimal condition was determined to approach to the maximum entrapment efficiency. The drug release profile of the optimal formulated material was examined in aqueous media and 64% of the Paromomycin loaded in SLNs was gradually released during 24 h, which reveals efficient prolonged release of the drug.

Research paper thumbnail of Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

International Journal of Nanomedicine, 2010

This study concerns the supercritical antisolvent process which allows single-step production of ... more This study concerns the supercritical antisolvent process which allows single-step production of 5-fluorouracil (5-FU) nanoparticles. This process enhances the physical characteristics of 5-FU in order to deliver it directly to the respiratory tract. Several mixtures of methanol with dichloromethane, acetone, or ethanol were used for particle preparation, and their effects on the physical characteristics of the final products were studied. The conditions of the experiment included pressures of 100 and 150 bar, temperature of 40°C, and a flow rate of 1 mL/min. The particles were characterized physicochemically before and after the process for their morphology and crystallinity. In spite of differences in size, the particles were not very different regarding their morphology. The resulting particles were of a regular shape, partly spherical, and appeared to have a smooth surface, whereas the mechanically milled particles showed less uniformity, had surface irregularities and a high particle size distribution, and seemed aggregated. Particles of 5-FU precipitated from methanol-dichloromethane 50:50 had a mean particle size of 248 nm. In order to evaluate the aerodynamic behavior of the nanoparticles, six 5-FU dry powder formulations containing mixtures of coarse and fine lactose of different percentages were prepared. Deposition of 5-FU was measured using a twin-stage liquid impinger and analyzed using a validated high pressure liquid chromatography method. Addition of fine lactose improved the aerodynamic performance of the drug, as determined by the fine particle fraction.

Research paper thumbnail of Three phase liquid phase microextraction of phenylacetic acid and phenylpropionic acid from biological fluids

Journal of Chromatography B, 2007

Three phase liquid phase microextraction (three phase LPME) technique coupled with HPLC-UV has be... more Three phase liquid phase microextraction (three phase LPME) technique coupled with HPLC-UV has been applied as a sensitive and efficient sample preparation method to determine phenylacetic acid (PAA) as a biomarker of depressive disorders and phenylpropionic acid (PPA) in biological fluids. The compounds were extracted from 3.0 ml aqueous solution with the adjustment of pH at a fixed value in the range of 2.0-3.5 (donor solution) into an organic phase (1-hexanol) layered on the surface of the donor solution and finally back-extracted into 4.0 l of the acceptor microdrop (pH 11.1) located at the end of the microsyringe needle. After a prescribed back-extraction time, the acceptor microdrop was withdrawn into the microsyringe and then directly injected into the HPLC system. In order to achieve maximum extraction efficiency, different parameters affecting the extraction conditions were optimized. At the optimum conditions (donor solution: 2.3 M Na 2 SO 4 , pH 2.0-3.5; organic membrane: 95 l of 1-hexanol; acceptor solution: 4.0 l of 0.1 M NH 3 /NH 4 + with pH 11.1; donor solution temperature: 45-50 • C; extraction time: 20 min and back-extraction time: 12 min), up to 110-fold enrichment factor was obtained. The calibration curve for these analytes was linear in the range of 1-5000 g/l with r 2 > 0.998. The intraday and interday RSD% were below 6.5% and the limits of detection (LODs) for both analytes were 0.2 g/l (based on S/N = 3). The proposed technique is a low cost, simple and sensitive method with highly clean-up effect. Finally, this technique was successfully utilized for the detection of target analytes in human urine, serum and plasma.

Research paper thumbnail of Effects of combined therapy with thalidomide and glucantime on leishmaniasis induced by Leishmania major in BALB/c mice

The Korean journal of …, 2006

For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with g... more For treating Leishmania major infection in BALB/c mice, we used thalidomide in conjunction with glucantime. Groups of mice were challenged with 5× 10 3 metacyclic promastigotes of L. major subcutaneously. A week after the challenge, drug treatment was ...

Research paper thumbnail of Effect of formulation ingredients on the physical characteristics of salmeterol xinafoate microparticles tailored by spray freeze drying

Advanced Powder Technology, 2013

ABSTRACT Series of microparticles containing salmeterol xinafoate (SX) as active pharmaceutical i... more ABSTRACT Series of microparticles containing salmeterol xinafoate (SX) as active pharmaceutical ingredient (API) and lactose, mannitol or trehalose as a bulking agents were prepared using spray freeze drying (SFD) technique and the effects of sugar type and presence of hydroxy propyl beta cyclodextrin (HPβCD) on the physical properties of powders were evaluated. Precipitation of salmeterol in the presence of lactose and mannitol resulted in the formation of irregular shapes of microparticles with broad size distributions. However application of trehalose resulted in the formation of porous particles with spherical morphology. Addition of cyclodextrin in the formulations was generally helpful for formation of porous and spherical particles with narrow size distribution with a mean size of 10–30 μm. Dissolution of SX from processed particles was substantially higher (∼90% drug release in 30 min) than that of unprocessed drug and physical mixture of drug and cyclodextrin (∼22% drug release in 30 min). This study showed that, processing of SX by SFD technique could be a constructive approach to the production of various forms of drug and drastic changes in the physical characteristics of microparticles could be achieved by changing the composition of bulking agent and cyclodextrin.