A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit va... more A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit vancomycin (VCM) nanoparticles prepared by double emulsion. The purpose of this work was to optimize VCM nanoparticles to improve the physicochemical properties. Nanoparticles were formed by using W1/O/W2 double-emulsion solvent evaporation method using Eudragit RS as a retardant material. Full factorial design was employed to study the effect of independent variables, RPM (X1), amount of emulsifier (X2), stirring rate (X3), volume of organic phase (X4) and volume of aqueous phase (X5), on the dependent variables as production yield, encapsulation efficiency and particle size. The optimum condition for VCM nanoparticles preparation was 1:2 drug to polymer ratio, 0.2 (%w/w) amount of emulsifier, 25 mL (volume of organic phase), 25 mL (volume of aqueous phase), 3 min (time of stirring) and 26000 RPM. RPM and emulsifier concentrations were the effective factors on the drug
Single-pass intestinal perfusion technique (SPIP) is the most used classic technique employed in ... more Single-pass intestinal perfusion technique (SPIP) is the most used classic technique employed in the study of intestinal absorption of compounds in which a non-absorbable marker such as phenol red is used to correct the water flux. A simple and rapid reversed-phase high performance liquid chromatographic method with UV detection at 227 nm was developed for simultaneous quantitation of propranolol and metoprolol along with phenol red for in-situ permeability studies. The mobile phase was a mixture of 55% methanol, 45% of 0.05 M KH 2 PO 4 aqueous solution (adjusted to pH 6) and 0.2 % (v/v) triethylamine. Analysis was run at a flow rate of 1 ml/min with a 9 min run time. The calibration curves were linear for all three compounds (r > 0.999) across the concentration range of 7.5-125 µg/ml with a limit of detection of 4.24, 2.18 and 8.57 ng/ml and limit of quantification of 14, 7.2 and 28.3 ng/ml for metoprolol, propranolol and phenol red respectively. The coefficient of variation for intra-assay and interassay precision was less than 8% and the accuracy was between 93.6-107%. Using the SPIP technique and the suggested HPLC method for sample analysis, the mean values of 0.49 e-4 (±0.19) cm/sec and 0.32 e-4 (± 0.09) cm/sec were obtained for propranolol and metoprolol intestinal permeability coefficients respectively.
The aim of the study was the prediction of human intestinal permeability and fraction absorbed of... more The aim of the study was the prediction of human intestinal permeability and fraction absorbed of oral dose using single-pass intestinal perfusion technique (SPIP) in rats. Permeability coefficients in anaesthetized rats were determined for 14 compounds. Drug solution in phosphate buffered saline (PBS) was perfused through a ingle-pass intestinal perfusion (SPIP) with flow rate of 0.21 ml/min and samples were taken from outlet tubing at different time points up to 90 min. Phenol red was used as a non-absorbable marker to correct water flux through the segment. Drug concentrations in samples were determined using HPLC and permeability coefficients (Peff) were calculated. The examined compounds demonstrated approximately 12.5 fold difference in magnitude for rat permeability coefficients among themselves. These values were compared with published data for human intestinal permeability, and a strong correlation was found between Peff (rat) and Peff (human); (Peff (human) = 11.04 Peff (...
A simple reversed-phase high-performance liquid chromatography (HPLC) method with ultraviolet det... more A simple reversed-phase high-performance liquid chromatography (HPLC) method with ultraviolet detection at 280 nm was developed for simultaneous quantitation of furosemide and hydrochlorothiazide along with phenol red as a nonabsorbable marker for in situ permeability studies in anaesthetized rats. A jejunal segment of approximately 10 cm was isolated and cannulated in both ends for inlet and outlet solution. The perfusate was collected every 10 min, and samples were analyzed using the developed method. The mobile phase was acetonitrile-water-triethylamine-glacial acetic acid (41.5 + 57.4 + 0.1 + 0.9, adjusted to pH 5.6) at a flow rate of 1 mL/min; the run time was 9 min. The calibration graphs were linear for all 3 compounds (r > 0.999) across the concentration range of 7.93-125 microg/mL for phenol red and 6.25-100 microg/mL for hydrochlorothiazide and furosemide. The limits of quantitation were 7.2, 8.9, and 6.8 microg/mL for furosemide, hydrochlorothiazide, and phenol red, re...
The aim of this study was to investigate the relationship between the intestinal absorption of st... more The aim of this study was to investigate the relationship between the intestinal absorption of structurally diverse model drugs across the rat intestinal mucosa and their molecular properties. Permeability coefficients for 13 compounds were determined in anaesthetized rats. Drug solution in phosphate buffered saline (PBS) was perfused through the intestinal segment with flow rate of 0.21 ml/min and samples were taken from outlet tubing at different time points up to 90 min. The permeability values ranged from 1.6×10 -5 to 2 ×10-4 cm/sec for atenolol and ibuprofen respectively. Molecular properties of drugs including the number of hydrogen bond donors and acceptors, log P, logD, topological polar surface area and number of rotatable bonds were considered. The results indicated that compounds which meet 10 or fewer number of rotatable bonds and topological surface area equal to or less than 140 A° have a high probability of good intestinal permeability and fraction of dose which is ab...
Objectives: Clarithromycin is a semi synthetic antibiotic from macrolid group that bind to 50 S r... more Objectives: Clarithromycin is a semi synthetic antibiotic from macrolid group that bind to 50 S ribosomal subunit of susceptible bacteria and inhibit essential bacterial protein synthesis. The purpose of this study is to prepare Clarithromycin-PLGA nanoparticles and to evaluate their antibacterial properties. Methods: Modified Quasi Emulsion Solvent Diffusion (MQESD) method was applied to prepare the Clarithromycin nanoparticles. Clarithromycin and PLGA were dissolved in acetone as a water miscible solvent and added to aqueous phase containing PVA2% as emulsifier and stabilizer agent, under homogenization. This led to formation of a quasi emulsion that contains Clarithromycin and PLGA and acetone in the inner phase. The microbial culture method was used to compare the effectiveness of nanosuspensions with untreated drug. Staphylococcus aureus PTCC 1112 and Salmonella typhi PTCC 1609 were used in this method. Minimum inhibitory concentration of clarithromycin nanosuspension was compared to those of clarithromycin solution. Results: Minimum inhibitory concentration of nanosuspensions in comparison with those of drug solution was significantly higher. This increased potency of formulated nanosuspensions is perhaps related to increased drug adsorption as well as lower drug degradation and modified surface characteristics. Conclusion: Our results indicate that clarithromycin in the form of nanosuspension has better antibacterial effect in comparison with untreated drug in the same drug concentration.
Purpose: Cell-penetrating peptides (CPPs) are used for delivering drugs and other macromolecular ... more Purpose: Cell-penetrating peptides (CPPs) are used for delivering drugs and other macromolecular cargo into living cells. In this paper, we investigated the relationship between the structural/physicochemical properties of four new synthetic peptides containing arginine-tryptophan in terms of their cell membrane penetration efficiency. Methods: The peptides were prepared using solid phase synthesis procedure using FMOC protected amino acids. Fluorescence-activated cell sorting and fluorescence imaging were used to evaluate uptake efficiency. Prediction of the peptide secondary structure and estimation of physicochemical properties was performed using the GOR V method and MPEx 3.2 software (Wimley-White scale, helical wheel projection and total hydrophobic moment). Results: Our data showed that the uptake efficiency of peptides with two tryptophans at the Cand N-terminus were significantly higher (about 4-fold) than that of peptides containing three tryptophans at both ends. The distribution of arginine at both ends also increased the uptake efficiency 2.52-and 7.18-fold, compared with arginine distribution at the middle of peptides. Conclusion: According to the obtained results the value of transfer free energies of peptides from the aqueous phase to membrane bilayer could be a good predictor for the cellular uptake efficiency of CPPs. | 167 Peptides uptake and thermodynamic and structural properties
Artificial cells, nanomedicine, and biotechnology, Jan 17, 2015
Quantum dots (QDs), as a new class of fluorescent tags, have been widely used for biomedical appl... more Quantum dots (QDs), as a new class of fluorescent tags, have been widely used for biomedical applications. Despite their various advantages, QDs do not efficiently enter cells on their own, and aggregation often occurs following internalization. In the present study, we have designed three QD-cell-penetrating peptide (CPP) complexes to increase the uptake of QD into cells. The results demonstrated that R9 and R5W3R4 form relatively stable noncovalent complexes with QDs, considerably increasing the rate and efficiency of QD uptake by A549 cells. These data suggest that cationic CPPs could efficiently transfer QDs into cells in a non-toxic manner.
The purpose of this paper is to enhance the solubility of clarithromycin (CLR) using nonionic sur... more The purpose of this paper is to enhance the solubility of clarithromycin (CLR) using nonionic surfactants and some type of acids for preparation of the new formulations. Myrj 52 and chremophor (2.5 and 5% w/v) were used in two concentrations. To investigate solubility, the formulations were shaken for 48 hours at room temperature. For stability test, lyophilized samples were maintained in refrigerator at 4° C, and in oven at 40° C. Drug analysis was performed by reverse phase high performance liquid chromatography (HPLC) with ultraviolet detection. Solubility tests indicated that lactobionic acid was the most effective to increase clarithromycin solubility and chremophor showed higher enhancing effect than myrj 52 on CLR solubility. The stability tests results also confirmed that shelf-lives of all formulations have been the equivalent to 24 months. On the whole, formulations described in this article may be very suitable for industrial-scale manufacturing and clinical application.
Azithromycin (AZI) is a new macrolide antibiotic with a better activity against intracellular gra... more Azithromycin (AZI) is a new macrolide antibiotic with a better activity against intracellular gram negative bacteria in comparison with Erythromycin. The purpose of this research was to prepare AZI nanoparticles (NPs) using PLGA polymer and to compare the effectiveness of prepared nanoparticles with untreated AZI solution. AZI NPs were prepared by Modified Quasi-Emulsion Solvent Diffusion method. The antibacterial activities of prepared NPs in comparison with AZI solution were assayed against indicator bacteria of Escherichia coli (PTCC 1330), Haemophilus influenzae (PTCC 1623) and Streptococcus pneumoniae (PTCC 1240) using agar well diffusion. Inhibition zone diameters (IZD) of nano-formulation were compared to the corresponding untreated AZI. Mean Inhibitory Concentration (MIC) values of AZI were also determined using serial dilution method in nutrient broth medium. Mean IZD of nano-formulations for all indicator bacteria were significantly higher than that of untreated AZI (P<...
The aim of the present study was to develop a simple and rapid reversed-phase high performance li... more The aim of the present study was to develop a simple and rapid reversed-phase high performance liquid chromatographic method with UV detection for erlotinib hydrochloride quantification, which is applicable for protein binding studies. Ultrafilteration method was used for protein binding study of erlotinib hydrochloride. For sample analysis a simple and rapid reversed-phase high performance liquid chromatographic method with UV detection at 332 nm was developed. The mobile phase was a mixture of methanol, acetonitril and potassium dihydrogen phosphate buffer (15:45:40 %v/v) set at flow rate of 1.3 ml/min. The run time for erlotinib hydrochloride was approximately 6 minutes. The calibration curve was linear over the range of 320-20000 ng/ml with acceptable intra- and inter-day precision and accuracy. The intra-day and inter-day precisions were less than 10% and the accuracies of intra and inter-day assays were within the range of 97.20-104.83% and 98.8-102.2% respectively. Based on t...
The major limitation in the widespread use of liposome drug delivery system is its instability. L... more The major limitation in the widespread use of liposome drug delivery system is its instability. Lyophilization is a promising approach to ensure the long-term stability of liposomes. The aim of this study was to prepare sirolimus-loaded liposomes, study their stability and investigate the effect of lyophilization either in the presence or in the absence of lyoprotectant on liposome properties. Two types of multi-lamellar liposomes, conventional and fusogenic, containing sirolimus were prepared by modified thin film hydration method with different ratio of dipalmitoylphosphatidylcholine (DPPC), cholesterol and dioleoylphosphoethanolamine (DOPE), and were lyophilized with or without dextrose as lyoprotectant. Chemical stability investigation was performed at 4°C and 25°C until 6 months using a validated HPLC method. Physical stability was studied with determination of particle size (PS) and encapsulation efficiency (EE %) of formulations through 6 months. Chemical stability test at 4°...
Metformin is an oral anti-diabetic drug in the biguanide class. The goal of this study was to dev... more Metformin is an oral anti-diabetic drug in the biguanide class. The goal of this study was to develop gastric-retentive MH discs in order to prolong the retention of drug in gastric mucosa. Two groups of metformin hydrochloride (MH) mucoadhesive gastroretentive discs were prepared: (a) bilayered discs prepared by direct compression of powders containing polymers as Carbopol 934P (CP, mucoadhesive polymer) and ethylcellulose (EC, rotardant polymer), (b) multiple unit system (microparticle) discs prepared by the emulsification, solvent evaporation, and compression technique from microparticles using polymers CP and EC. Gastric-mucoadhesive compacts were evaluated by investigating their release pattern, swelling capacity, mucoadhesion property, surface pH, and in vitro gastro-retentive time. Discs formulation was subjected to disintegration and dissolution tests by placing in 0.1 M hydrochloric acid for 8 h. The production yield showed F2 microparticles of 98.80%, mean particle size of...
P-glycoprotein (P-gp; ABCB1), an integral membrane protein in the apical surface of human intesti... more P-glycoprotein (P-gp; ABCB1), an integral membrane protein in the apical surface of human intestinal epithelial cells, plays a crucial role in the intestinal transport and efflux leading to changes in the bioavailability of oral pharmaceutical compounds. This study was set to examine the potential effects of three Eudragits RL100, S100 and L100 on the intestinal epithelial membrane transport of rhodammine-123 (Rho-123), a substrate of P-gp using a monolayer of human colon cancer cell line (Caco-2). The least non-cytotoxic concentrations of the excipients were assessed in Caco-2 cells by the MTT assay. Then the transepithelial transport of Rho-123 across Caco-2 monolayers was determined with a fluorescence spectrophotometer. Besides, the expression of the P-gp in cells exposed to the polymers was demonstrated using Western-blotting analysis. Treatment of cells with Eudragit RL100 and L100 led to a very slight change while Eudragit S100 showed 61% increase in Rho-123 accumulation (P&l...
Iranian journal of pharmaceutical research : IJPR, 2012
A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit va... more A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit vancomycin (VCM) nanoparticles prepared by double emulsion. The purpose of this work was to optimize VCM nanoparticles to improve the physicochemical properties. Nanoparticles were formed by using W1/O/W2 double-emulsion solvent evaporation method using Eudragit RS as a retardant material. Full factorial design was employed to study the effect of independent variables, RPM (X1), amount of emulsifier (X2), stirring rate (X3), volume of organic phase (X4) and volume of aqueous phase (X5), on the dependent variables as production yield, encapsulation efficiency and particle size. The optimum condition for VCM nanoparticles preparation was 1:2 drug to polymer ratio, 0.2 (%w/w) amount of emulsifier , 25 mL (volume of organic phase), 25 mL (volume of aqueous phase), 3 min (time of stirring) and 26000 RPM. RPM and emulsifier concentrations were the effective factors on the drug loading (R2 = 90.8...
A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit va... more A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit vancomycin (VCM) nanoparticles prepared by double emulsion. The purpose of this work was to optimize VCM nanoparticles to improve the physicochemical properties. Nanoparticles were formed by using W1/O/W2 double-emulsion solvent evaporation method using Eudragit RS as a retardant material. Full factorial design was employed to study the effect of independent variables, RPM (X1), amount of emulsifier (X2), stirring rate (X3), volume of organic phase (X4) and volume of aqueous phase (X5), on the dependent variables as production yield, encapsulation efficiency and particle size. The optimum condition for VCM nanoparticles preparation was 1:2 drug to polymer ratio, 0.2 (%w/w) amount of emulsifier, 25 mL (volume of organic phase), 25 mL (volume of aqueous phase), 3 min (time of stirring) and 26000 RPM. RPM and emulsifier concentrations were the effective factors on the drug
Single-pass intestinal perfusion technique (SPIP) is the most used classic technique employed in ... more Single-pass intestinal perfusion technique (SPIP) is the most used classic technique employed in the study of intestinal absorption of compounds in which a non-absorbable marker such as phenol red is used to correct the water flux. A simple and rapid reversed-phase high performance liquid chromatographic method with UV detection at 227 nm was developed for simultaneous quantitation of propranolol and metoprolol along with phenol red for in-situ permeability studies. The mobile phase was a mixture of 55% methanol, 45% of 0.05 M KH 2 PO 4 aqueous solution (adjusted to pH 6) and 0.2 % (v/v) triethylamine. Analysis was run at a flow rate of 1 ml/min with a 9 min run time. The calibration curves were linear for all three compounds (r > 0.999) across the concentration range of 7.5-125 µg/ml with a limit of detection of 4.24, 2.18 and 8.57 ng/ml and limit of quantification of 14, 7.2 and 28.3 ng/ml for metoprolol, propranolol and phenol red respectively. The coefficient of variation for intra-assay and interassay precision was less than 8% and the accuracy was between 93.6-107%. Using the SPIP technique and the suggested HPLC method for sample analysis, the mean values of 0.49 e-4 (±0.19) cm/sec and 0.32 e-4 (± 0.09) cm/sec were obtained for propranolol and metoprolol intestinal permeability coefficients respectively.
The aim of the study was the prediction of human intestinal permeability and fraction absorbed of... more The aim of the study was the prediction of human intestinal permeability and fraction absorbed of oral dose using single-pass intestinal perfusion technique (SPIP) in rats. Permeability coefficients in anaesthetized rats were determined for 14 compounds. Drug solution in phosphate buffered saline (PBS) was perfused through a ingle-pass intestinal perfusion (SPIP) with flow rate of 0.21 ml/min and samples were taken from outlet tubing at different time points up to 90 min. Phenol red was used as a non-absorbable marker to correct water flux through the segment. Drug concentrations in samples were determined using HPLC and permeability coefficients (Peff) were calculated. The examined compounds demonstrated approximately 12.5 fold difference in magnitude for rat permeability coefficients among themselves. These values were compared with published data for human intestinal permeability, and a strong correlation was found between Peff (rat) and Peff (human); (Peff (human) = 11.04 Peff (...
A simple reversed-phase high-performance liquid chromatography (HPLC) method with ultraviolet det... more A simple reversed-phase high-performance liquid chromatography (HPLC) method with ultraviolet detection at 280 nm was developed for simultaneous quantitation of furosemide and hydrochlorothiazide along with phenol red as a nonabsorbable marker for in situ permeability studies in anaesthetized rats. A jejunal segment of approximately 10 cm was isolated and cannulated in both ends for inlet and outlet solution. The perfusate was collected every 10 min, and samples were analyzed using the developed method. The mobile phase was acetonitrile-water-triethylamine-glacial acetic acid (41.5 + 57.4 + 0.1 + 0.9, adjusted to pH 5.6) at a flow rate of 1 mL/min; the run time was 9 min. The calibration graphs were linear for all 3 compounds (r > 0.999) across the concentration range of 7.93-125 microg/mL for phenol red and 6.25-100 microg/mL for hydrochlorothiazide and furosemide. The limits of quantitation were 7.2, 8.9, and 6.8 microg/mL for furosemide, hydrochlorothiazide, and phenol red, re...
The aim of this study was to investigate the relationship between the intestinal absorption of st... more The aim of this study was to investigate the relationship between the intestinal absorption of structurally diverse model drugs across the rat intestinal mucosa and their molecular properties. Permeability coefficients for 13 compounds were determined in anaesthetized rats. Drug solution in phosphate buffered saline (PBS) was perfused through the intestinal segment with flow rate of 0.21 ml/min and samples were taken from outlet tubing at different time points up to 90 min. The permeability values ranged from 1.6×10 -5 to 2 ×10-4 cm/sec for atenolol and ibuprofen respectively. Molecular properties of drugs including the number of hydrogen bond donors and acceptors, log P, logD, topological polar surface area and number of rotatable bonds were considered. The results indicated that compounds which meet 10 or fewer number of rotatable bonds and topological surface area equal to or less than 140 A° have a high probability of good intestinal permeability and fraction of dose which is ab...
Objectives: Clarithromycin is a semi synthetic antibiotic from macrolid group that bind to 50 S r... more Objectives: Clarithromycin is a semi synthetic antibiotic from macrolid group that bind to 50 S ribosomal subunit of susceptible bacteria and inhibit essential bacterial protein synthesis. The purpose of this study is to prepare Clarithromycin-PLGA nanoparticles and to evaluate their antibacterial properties. Methods: Modified Quasi Emulsion Solvent Diffusion (MQESD) method was applied to prepare the Clarithromycin nanoparticles. Clarithromycin and PLGA were dissolved in acetone as a water miscible solvent and added to aqueous phase containing PVA2% as emulsifier and stabilizer agent, under homogenization. This led to formation of a quasi emulsion that contains Clarithromycin and PLGA and acetone in the inner phase. The microbial culture method was used to compare the effectiveness of nanosuspensions with untreated drug. Staphylococcus aureus PTCC 1112 and Salmonella typhi PTCC 1609 were used in this method. Minimum inhibitory concentration of clarithromycin nanosuspension was compared to those of clarithromycin solution. Results: Minimum inhibitory concentration of nanosuspensions in comparison with those of drug solution was significantly higher. This increased potency of formulated nanosuspensions is perhaps related to increased drug adsorption as well as lower drug degradation and modified surface characteristics. Conclusion: Our results indicate that clarithromycin in the form of nanosuspension has better antibacterial effect in comparison with untreated drug in the same drug concentration.
Purpose: Cell-penetrating peptides (CPPs) are used for delivering drugs and other macromolecular ... more Purpose: Cell-penetrating peptides (CPPs) are used for delivering drugs and other macromolecular cargo into living cells. In this paper, we investigated the relationship between the structural/physicochemical properties of four new synthetic peptides containing arginine-tryptophan in terms of their cell membrane penetration efficiency. Methods: The peptides were prepared using solid phase synthesis procedure using FMOC protected amino acids. Fluorescence-activated cell sorting and fluorescence imaging were used to evaluate uptake efficiency. Prediction of the peptide secondary structure and estimation of physicochemical properties was performed using the GOR V method and MPEx 3.2 software (Wimley-White scale, helical wheel projection and total hydrophobic moment). Results: Our data showed that the uptake efficiency of peptides with two tryptophans at the Cand N-terminus were significantly higher (about 4-fold) than that of peptides containing three tryptophans at both ends. The distribution of arginine at both ends also increased the uptake efficiency 2.52-and 7.18-fold, compared with arginine distribution at the middle of peptides. Conclusion: According to the obtained results the value of transfer free energies of peptides from the aqueous phase to membrane bilayer could be a good predictor for the cellular uptake efficiency of CPPs. | 167 Peptides uptake and thermodynamic and structural properties
Artificial cells, nanomedicine, and biotechnology, Jan 17, 2015
Quantum dots (QDs), as a new class of fluorescent tags, have been widely used for biomedical appl... more Quantum dots (QDs), as a new class of fluorescent tags, have been widely used for biomedical applications. Despite their various advantages, QDs do not efficiently enter cells on their own, and aggregation often occurs following internalization. In the present study, we have designed three QD-cell-penetrating peptide (CPP) complexes to increase the uptake of QD into cells. The results demonstrated that R9 and R5W3R4 form relatively stable noncovalent complexes with QDs, considerably increasing the rate and efficiency of QD uptake by A549 cells. These data suggest that cationic CPPs could efficiently transfer QDs into cells in a non-toxic manner.
The purpose of this paper is to enhance the solubility of clarithromycin (CLR) using nonionic sur... more The purpose of this paper is to enhance the solubility of clarithromycin (CLR) using nonionic surfactants and some type of acids for preparation of the new formulations. Myrj 52 and chremophor (2.5 and 5% w/v) were used in two concentrations. To investigate solubility, the formulations were shaken for 48 hours at room temperature. For stability test, lyophilized samples were maintained in refrigerator at 4° C, and in oven at 40° C. Drug analysis was performed by reverse phase high performance liquid chromatography (HPLC) with ultraviolet detection. Solubility tests indicated that lactobionic acid was the most effective to increase clarithromycin solubility and chremophor showed higher enhancing effect than myrj 52 on CLR solubility. The stability tests results also confirmed that shelf-lives of all formulations have been the equivalent to 24 months. On the whole, formulations described in this article may be very suitable for industrial-scale manufacturing and clinical application.
Azithromycin (AZI) is a new macrolide antibiotic with a better activity against intracellular gra... more Azithromycin (AZI) is a new macrolide antibiotic with a better activity against intracellular gram negative bacteria in comparison with Erythromycin. The purpose of this research was to prepare AZI nanoparticles (NPs) using PLGA polymer and to compare the effectiveness of prepared nanoparticles with untreated AZI solution. AZI NPs were prepared by Modified Quasi-Emulsion Solvent Diffusion method. The antibacterial activities of prepared NPs in comparison with AZI solution were assayed against indicator bacteria of Escherichia coli (PTCC 1330), Haemophilus influenzae (PTCC 1623) and Streptococcus pneumoniae (PTCC 1240) using agar well diffusion. Inhibition zone diameters (IZD) of nano-formulation were compared to the corresponding untreated AZI. Mean Inhibitory Concentration (MIC) values of AZI were also determined using serial dilution method in nutrient broth medium. Mean IZD of nano-formulations for all indicator bacteria were significantly higher than that of untreated AZI (P<...
The aim of the present study was to develop a simple and rapid reversed-phase high performance li... more The aim of the present study was to develop a simple and rapid reversed-phase high performance liquid chromatographic method with UV detection for erlotinib hydrochloride quantification, which is applicable for protein binding studies. Ultrafilteration method was used for protein binding study of erlotinib hydrochloride. For sample analysis a simple and rapid reversed-phase high performance liquid chromatographic method with UV detection at 332 nm was developed. The mobile phase was a mixture of methanol, acetonitril and potassium dihydrogen phosphate buffer (15:45:40 %v/v) set at flow rate of 1.3 ml/min. The run time for erlotinib hydrochloride was approximately 6 minutes. The calibration curve was linear over the range of 320-20000 ng/ml with acceptable intra- and inter-day precision and accuracy. The intra-day and inter-day precisions were less than 10% and the accuracies of intra and inter-day assays were within the range of 97.20-104.83% and 98.8-102.2% respectively. Based on t...
The major limitation in the widespread use of liposome drug delivery system is its instability. L... more The major limitation in the widespread use of liposome drug delivery system is its instability. Lyophilization is a promising approach to ensure the long-term stability of liposomes. The aim of this study was to prepare sirolimus-loaded liposomes, study their stability and investigate the effect of lyophilization either in the presence or in the absence of lyoprotectant on liposome properties. Two types of multi-lamellar liposomes, conventional and fusogenic, containing sirolimus were prepared by modified thin film hydration method with different ratio of dipalmitoylphosphatidylcholine (DPPC), cholesterol and dioleoylphosphoethanolamine (DOPE), and were lyophilized with or without dextrose as lyoprotectant. Chemical stability investigation was performed at 4°C and 25°C until 6 months using a validated HPLC method. Physical stability was studied with determination of particle size (PS) and encapsulation efficiency (EE %) of formulations through 6 months. Chemical stability test at 4°...
Metformin is an oral anti-diabetic drug in the biguanide class. The goal of this study was to dev... more Metformin is an oral anti-diabetic drug in the biguanide class. The goal of this study was to develop gastric-retentive MH discs in order to prolong the retention of drug in gastric mucosa. Two groups of metformin hydrochloride (MH) mucoadhesive gastroretentive discs were prepared: (a) bilayered discs prepared by direct compression of powders containing polymers as Carbopol 934P (CP, mucoadhesive polymer) and ethylcellulose (EC, rotardant polymer), (b) multiple unit system (microparticle) discs prepared by the emulsification, solvent evaporation, and compression technique from microparticles using polymers CP and EC. Gastric-mucoadhesive compacts were evaluated by investigating their release pattern, swelling capacity, mucoadhesion property, surface pH, and in vitro gastro-retentive time. Discs formulation was subjected to disintegration and dissolution tests by placing in 0.1 M hydrochloric acid for 8 h. The production yield showed F2 microparticles of 98.80%, mean particle size of...
P-glycoprotein (P-gp; ABCB1), an integral membrane protein in the apical surface of human intesti... more P-glycoprotein (P-gp; ABCB1), an integral membrane protein in the apical surface of human intestinal epithelial cells, plays a crucial role in the intestinal transport and efflux leading to changes in the bioavailability of oral pharmaceutical compounds. This study was set to examine the potential effects of three Eudragits RL100, S100 and L100 on the intestinal epithelial membrane transport of rhodammine-123 (Rho-123), a substrate of P-gp using a monolayer of human colon cancer cell line (Caco-2). The least non-cytotoxic concentrations of the excipients were assessed in Caco-2 cells by the MTT assay. Then the transepithelial transport of Rho-123 across Caco-2 monolayers was determined with a fluorescence spectrophotometer. Besides, the expression of the P-gp in cells exposed to the polymers was demonstrated using Western-blotting analysis. Treatment of cells with Eudragit RL100 and L100 led to a very slight change while Eudragit S100 showed 61% increase in Rho-123 accumulation (P&l...
Iranian journal of pharmaceutical research : IJPR, 2012
A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit va... more A Box-Behnken design with three replicates was used for preparation and evaluation of Eudragit vancomycin (VCM) nanoparticles prepared by double emulsion. The purpose of this work was to optimize VCM nanoparticles to improve the physicochemical properties. Nanoparticles were formed by using W1/O/W2 double-emulsion solvent evaporation method using Eudragit RS as a retardant material. Full factorial design was employed to study the effect of independent variables, RPM (X1), amount of emulsifier (X2), stirring rate (X3), volume of organic phase (X4) and volume of aqueous phase (X5), on the dependent variables as production yield, encapsulation efficiency and particle size. The optimum condition for VCM nanoparticles preparation was 1:2 drug to polymer ratio, 0.2 (%w/w) amount of emulsifier , 25 mL (volume of organic phase), 25 mL (volume of aqueous phase), 3 min (time of stirring) and 26000 RPM. RPM and emulsifier concentrations were the effective factors on the drug loading (R2 = 90.8...
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Papers by Parvin Zakeri