The purpose of this study was to evaluate the bioavailability of locally produced 2.5 mg terbutal... more The purpose of this study was to evaluate the bioavailability of locally produced 2.5 mg terbutaline sulphate tablets (brand A ) relative to a reference product, Bricanyl 2.5 mg tablets (brand 6). The study was a single dose 5 mg randomized crossover one in 15 healthy volunteers in the fasting state. Urine was collected at intervals of 24 h. Total terbutaline excreted in urine as unchanged drug and as conjugates (sulphate and glucuronide) was determined by a developed and validated HPLC method. In-vitro characteristics of both brands were similar. Based on percent of the dose excreted in urine, the oral bioavailability ranged from 33.5% to 75.8% for both brands. Statistics were applied to judge bioequivalence according to USP 24 in-vivo bioequivalence guidance. Results indicated that brand A and B were bioequivalent and hence interchangeable in medical practice.
Journal of Drug Delivery Science and Technology, 2012
Liquisolid compacts of diltiazem hydrochloride (DTZ) were prepared using three different methods ... more Liquisolid compacts of diltiazem hydrochloride (DTZ) were prepared using three different methods to sustain the drug release rate. Ethyl cellulose, hydroxypropyl methylcellulose and Sterotex were used separately in this study as adjuvant in the first method of preparation and as carriers in the second method. These two methods involved the addition of the binary mixture of carrier-coating materials to the liquid medication in propylene glycol under continuous stirring. The third method of preparation involved the addition of the dispersed medication in Tween 20 to the binary mixture of carrier and coating materials. The final mixtures were then subjected to thermal analysis and flowability studies before compaction into tablets. DTZ tablets prepared by the liquisolid technique were subjected to dissolution rate studies to determine the release rate of the drug in comparison with the conventional tablets. Formulations containing HPMC prepared by the different techniques showed promising extended release of the drug, followed by formulations containing EC. Formulations containing Sterotex showed the least drug release-retardation effect. Release kinetic studies revealed that the release obeyed Higuchi's model.
The aim of this study was to formulate stable film-coated montelukast sodium (MS) tablets using O... more The aim of this study was to formulate stable film-coated montelukast sodium (MS) tablets using Opadry ® yellow 20A82938 (Montikast ® tablets) and to evaluate their in vitro and in vivo release profile. Methods: MS core tablets were manufactured using a direct compression method. Opadry yellow 20A82938 aqueous coating dispersion was used as the film-coating material. Dissolution of the film-coated tablets was tested in 900 mL of 0.5% sodium lauryl sulfate solution and the bioequivalence of the tablets was tested by comparing them with a reference formulation-Singulair ® tablets. In vitro-in vivo correlation was evaluated. The stability of the obtained film-coated tablets was evaluated according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. Results: The efficiency of the film coating was determined by subjecting the coated tablets to gastric pH and drug release was analyzed using high-performance liquid chromatography. The coated tablets had no obvious defects. MS release met the study criterion of not less than 80% dissolved after 30 minutes in 0.5% sodium lauryl sulfate solution. Statistical comparison of the main pharmacokinetic parameters clearly indicated no significant difference between test and reference in any of the calculated pharmacokinetic parameters. Level A correlation between in vitro drug release and in vivo absorption was found to be satisfactory. Conclusion: These findings suggest that aqueous film coating with Opadry yellow 20A82938 is an easy, reproducible, and economical approach for preparing stable MS film-coated tablets without affecting the drug-release characteristics.
T he objective of the present study was to investigate the potential of microemulsion formulation... more T he objective of the present study was to investigate the potential of microemulsion formulations for transdermal delivery of indomethacin (IND). Microemulsion formulations with different surfactant:cosurfactant ratios (S mix); F1-F6 (1:1, 2:2, 3:1, 4:1, 1:2, and 3:2) were prepared by the spontaneous emulsification method, and characterized for morphology, droplet size, and rheological characteristics. The ex vivo skin permeation studies were performed using Franz diffusion cell with rabbit skin as a permeation membrane. A significant increase in the steady-state flux (J ss), permeability coefficient (K p), and enhancement ratio (E r) was observed in microemulsion formulations compared with the conventional IND gel. The antiinflammatory effects of microemulsion formulations showed a significant increase in percent edema inhibition value after 4 hours. The optimized formulation showed a significant increase in the steady-state flux (J ss) and permeability coefficient (K p). The enhancement ratio (E r) was found to be 8.939 in optimized formulation F1 compared with IND gel.
T he aim of the current study was to design oral controlled release (CR) theophylline anhydrous b... more T he aim of the current study was to design oral controlled release (CR) theophylline anhydrous bioadhesive tablets and to optimize the drug release profile and in vitro bioadhesion strength. Different types of natural hydrophilic polymers such as xanthun gum, locust bean gum, guar gum, karaya gum, and their combinations were used to formulate matrix tablets. Tablets of anhydrous theophylline were prepared by the direct compression method and were subjected to in vitro drug dissolution for 12 hours using the USP dissolution apparatus basket type at a speed of 100 rpm and temperature of 37 ± 0.5°C using gastric fluid (pH 1.2). The bioadhesive strength of the tablets was measured as the force of detachment against the porcine gastric mucosa. The in vitro release study as well as the retention time of the bioadhesive tablets on the mucous membrane were investigated to develop a bioadhesive polymer-based CR delivery system and to evaluate the performance of such a delivery device. The combination of karaya gum:guar gum (6:4) tablet showed a greater bioadhesive strength as compared with a single gum and other gum combination tablets. Karaya gum:guar gum-loaded tablets were not discharged from the mucous membrane and were dissolved in the gastric fluid. An increase in the gum concentration increases the drug release profile beyond 12 hours whereas there is no significant effect of gum concentration on the bioadhesive strength of the tablet.
The purpose of this study was to prepare a pressure-controlled colon delivery capsule (PCDC) cont... more The purpose of this study was to prepare a pressure-controlled colon delivery capsule (PCDC) containing theophylline (TPH) dispersion in a lipid matrix as a chronotherapeutic drug delivery system for the treatment of nocturnal asthma. The system was made by film coating using Eudragit S100- based formula over the sealed-hard gelatin capsules containing the drug-lipid dispersion. The lipid formula was composed mainly of Gelucire 33/01 (G33) with different ratios of surfactants (1-10%). The efficiency of the prepared system was evaluated in vitro for its ability to withstand both the gastric and intestinal medium. In addition, the drug plasma concentrations were monitored after single administration to Beagle dogs and compared to that obtained after administration of a reference marketed, generic, sustained-release TPH tablets, Avolen(®) SR. It was found that the optimum lipid formula was GL2 containing 90% G33 and 10% Labrasol. The film-coated capsules showed complete resistance to both the acidic environment (pH 1.2) for 2 hours and phosphate buffer pH 6.8 for 3 hours at 37°C. In vivo evaluation of the TPH-based PCDCs showed longer lag time compared TO the marketed formula followed by sudden increase in TPH blood levels, which recommends the high potential of this system as a chronotherapeutic drug delivery for nocturnal asthma. The prepared PCDCs exhibited a significantly higher C(max) and T(max) and a nonsignificantly different AUC compared with Avolen(®) SR. Higher TPH blood levels from 1 to 8 hours postadministration was detected in the case of the prepared PCDCs.
International Journal of Environmental Science & Technology, 2007
Desorption of Cu and low molecular weight dissolved organics are the primary factors that impact ... more Desorption of Cu and low molecular weight dissolved organics are the primary factors that impact fate and transport of Cu in soils. To improve predictions of the toxicity and threat from Cu contaminated soil, it is critical that time-dependent desorption behavior be understood. In this paper, the effect of organic ligands citrate, malate, and succinate on the kinetics of Cu desorption from contaminated soils varying widely in soil characteristics was investigated at 25 0 C and the soils used were referred to as clay, calcareous and sandy soils. The amount of Cu released by the used organic ligands varied greatly with physicochemical properties of the soils. The rate of Cu release by different extractants was in the order citric > malic > succinic, which was consistent with the stability constants of Cu complexes with these ligands. The modified Freundlich and the Elovich and Parabolic diffusion models were used to describe dsorption of Cu 2+ from the three studied soils as affected by the organic ligands. All of the models fit the data well with correlation coefficients ranging from 0.83 to 1.00 (P < 0.01). Each Model has a set of assumptions for the different physical and chemical properties of the systems to which they are being applied. The uses of these equations yield different magnitudes for the calculated variable, but the relationships between the soil + organic ligands and their effect (i.e., increase or decrease) on these variables are the same. Such information is critical, since Cu is used in a variety of industrial and manufacturing processes and is one of the most common contaminants found at hazardous waste sites.
Gliclazide (GLZ)-loaded microparticles made with a polymeric blend were prepared by a solvent eva... more Gliclazide (GLZ)-loaded microparticles made with a polymeric blend were prepared by a solvent evaporation technique. Organic solutions of two polymers, poly(ε-caprolactone) (PCL) and Eudragit RS (E RS) or ethyl cellulose (EC), in different weight ratios, and 33.3% of GLZ were prepared and dropped into aqueous solution of poly vinyl alcohol, in different experimental conditions, achieving drug-loaded microparticles. The obtained microparticles were characterized in terms of yield of production, shape, size, surface properties, drug content, and in vitro drug release behavior. The physical state of the drugs and the polymer was determined by scanning electron microscopy (SEM), Fourier transform infra red and differential scanning calorimetry. Following the in vitro release studies microparticles made from blends of polymer, PCL/E RS or EC showed slower drug release than microparticles made from single PCL polymer. Surface morphology also revealed presence of porous and spherical structure of microparticles. Microparticles showing sustained release of GLZ were examined in rabbits and plasma GLZ concentrations were calculated using HPLC method of assay.
Lipospheres of carbamazepine were prepared by melt dispersion technique using Precifac ATO 5 in t... more Lipospheres of carbamazepine were prepared by melt dispersion technique using Precifac ATO 5 in the various drug-lipid ratios. The resulting free-flowing lipospheres were evaluated with respect to surface morphology, particle size distribution, encapsulation efficiency, and in vitro release behavior. The effect of druglipid ratio, the surfactant added, emulsion stabilizer, and stirring speed also were identified as the key variables affecting the formation of discrete spherical lipospheres and drug release rate. The preparation conditions were optimized by using 0.4% w/v span 20 (Hydrophilic-Lipophilic Balance, HLB = 8.6) as a surfactant and 1% w/v gelatin solution as a stabilizer in presence of a high level of water. We found that the ratio of drug to lipid affects the size of the spheres. The incorporation efficiency was found to be high at all loadings. Increasing the lipid:drug ratio produced more spherical, smooth, and round lipospheres. All the prepared lipospheres exhibited slow release profiles dictating the Higuchi mode of release. We saw that the higher the sphere size and the ratio of Precifac, the slower is in vitro drug release.
Promising Pharmaceuticals 64 derivatives, allergenic patch tests and extracts, HIV and hepatitis ... more Promising Pharmaceuticals 64 derivatives, allergenic patch tests and extracts, HIV and hepatitis tests, gene therapy products, cells and tissues for transplantation, and new treatments for cancers, arthritis, and other serious diseases. CBER reviewed the first vaccines to immunize persons against infectious diseases, such as polio, pertussis ("whooping cough"), and German measles. CBER research led to important discoveries to safely collect, prepare, and transfuse blood and blood plasma. 2. Biological products, industry history (1) Biological products were created with biotechnology, the scientific and engineering procedures involved in manipulating organisms or biological components at the cellular, subcellular, or molecular level. These manipulations were carried out to make or modify plants and animals or other biological substances with desired traits. Although examples of primitive biotech processes dated back to ancient times (such as the use of fermentation in brewing and leavening agents in baking), their use in medical and pharmaceutical applications was an innovation of the latter decades of the twentieth century. Some analysts compared the biotech industry's impact on global medical care with the computer industry's impact on communication. Biotech researchers produced products in essentially three ways: by developing ways to achieve commercial production of naturally occurring substances; by genetically altering naturally occurring substances; and by creating entirely new substances. Some of the tools used by biotech researchers included recombinant DNA and monoclonal antibodies. Recombinant DNA involved the ability to take the deoxyribonucleic acid (DNA) from one organism and combine it with the DNA from another organism thereby creating new products and processes. By using recombinant DNA techniques researchers were able to select specific genes and introduce them into other cells or living organisms to create products with specific attributes. Monoclonal antibodies were developed from cultures of single cells using cloning techniques. They were designed for use in attacking toxins, viruses, and cancer cells. Because the biological products presented for approval often involved new technologies or innovative therapies for diseases that had not been previously treated successfully, the approval process frequently proved to be long and costly. Many companies struggled financially through the 1980s waiting for an FDA determination.
Gliclazide (GLZ)/Chitosan microparticles were prepared with tripolyphosphate (TPP) by ionic cross... more Gliclazide (GLZ)/Chitosan microparticles were prepared with tripolyphosphate (TPP) by ionic cross-linking. The particle sizes of TPP-chitosan microparticles were in the range 675-887 µm and the loading efficiencies of drug was more than 94.0%. Chitosan concentration, TPP solution pH and glutaraldehyde volume added to the TPP cross-linking solution had an effect on the drug release characteristics. The microparticles were examined with scanning electron microscopy and infrared spectroscopy. Furthermore, pectin can interact with cationic chitosan on the surface of these TPP/chitosan microparticles to form a polyelectrolyte complex film for the improvement of the drug sustained-release performances. In vivo testing of the GLZ-chitosan microparticles in diabetic albino rabbits demonstrated significant antidiabetic effect of GLZ/chitosan microparticles after 8 h which lasts for 18 h, compared with GLZ powder which produced maximum hypoglycaemic effect after 4 h, suggesting that GLZ/chitosan microparticles are a valuable system for the long-term delivery of GLZ.
European Journal of Pharmaceutics and Biopharmaceutics, 2009
IK312532), a long-acting VIP derivative, was proposed as potential drug candidate for the treatme... more IK312532), a long-acting VIP derivative, was proposed as potential drug candidate for the treatment of asthma/COPD. The present work is aimed to elucidate solutionstate stability of IK312532 and to develop further stabilized derivative with equipotent or higher biological functions. A stability study on IK312532 was carried out in solution state, and degradation mechanism was deduced by UPLC-MS and amino acid analyses. Three novel VIP derivatives were designed and chemically synthesized on the basis of stability data, being subjected to physicochemical and pharmacological characterization. Solution-state stability studies revealed the gradual degradation of IK312532, following pseudo-first-order kinetics. Chemical modification of IK312532, mainly position at 24, resulted in marked improvement of stability, although the chemical modification had no influence on the secondary structure, receptor binding, and activation of adenylate cyclase in rat lung cells. Novel derivatives also exhibited more potent neurite outgrowth in rat pheochromocytoma PC12 cells when compared to VIP and IK312532, possibly due to improved stability. Deamination of Asn at position 24 might be responsible for degradation of VIP derivative, and stability and chemical modification studies led us to the successful development of novel VIP derivatives with higher stability and biological functions.
Magnetic nanoparticles are attractive targets owing to their unique characteristics that are not ... more Magnetic nanoparticles are attractive targets owing to their unique characteristics that are not shared by bulk materials. Magnetic particles, ranging from nanometer-sized to 1 µm in size, are being used in an increasing number of medical applications. The important properties of magnetic particles for medical applications are nontoxicity, biocompatiblilty, injectability and high-level accumulation in the target tissue or organ. Magnetic nanoparticles modified with organic molecules have been widely used for biotechnological and biomedical applications as their properties can be magnetically controlled by applying an external magnetic field. They offer high potential for numerous biomedical applications, such as cell separation, automated DNA extraction, gene targeting, drug delivery, MRI and hyperthermia. When coated with, for example, an antibody, they can be applied in highly sensitive immunoassays or small substance recoveries. Furthermore, a novel application of magnetic nanopa...
Targeting the brain via nasal administration of drugs has been studied frequently over the last f... more Targeting the brain via nasal administration of drugs has been studied frequently over the last few years. In this study, a suitable gel formulation was designed to provide the absorption of a highly lipophilic drug through nasal mucosa. For this purpose, carbamazepine was chosen as the model drug. Hypromellose and Carbopol were used as mucoadhesive polymers in the formulation to increase the residence time of the gel on the mucosa. The objective of this study was to confirm the existence of a transport pathway for a drug (carbamazepine) to the brain directly from the nasal cavity, by comparing the concentration of drug in the brain after intranasal (i.n.), intravenous (i.v.), and oral (p.o.) administration. A statistically significant high level of the drug was found in the brain following intranasal administration compared with the intravenous and oral routes. These findings suggested the existence of a direct transport pathway for carbamazepine from the nasal cavity to the brain....
The aim of this study was to develop and characterize diclofenac sodium loaded-cellulose acetate ... more The aim of this study was to develop and characterize diclofenac sodium loaded-cellulose acetate butyrate microparticles in order to obtain a controlled-release system. The influence of the type of polymer, the volume and composition of the internal phase, drug loading, surfactant concentration and additive added on microparticles characteristics (particle size, encapsulation efficiency, surface morphology and in vitro release profiles) was studied to optimize the microparticles system. The resultant microparticles were evaluated for the recovery, average particle size, drug loading and incorporation efficiency. The microparticles exhibited good flowing nature and compressibility index when compared to pure drug. Dissolution rate of diclofenac sodium in phosphate buffer (pH 6.8) increased with increases in initial drug loading, surfactant concentration and addition of alcohol as co-solvent but decreased with increases in the concentration of additives such as Gantrez AN or Eudragit S100 in the internal phase. The dissolution data showed a Higuchi diffusion pattern for most of the formulations. About 56-81% reduction in ulcerogenic activity was observed with microparticles containing Eudragit S100 17-25%, based on total polymer concentration, when compared with pure diclofenac sodium.
The present study focuses on enhancement of the dissolution and oral absorption of poorly water‐s... more The present study focuses on enhancement of the dissolution and oral absorption of poorly water‐soluble etodolac. A self‐emulsifying drug delivery system (SEDDS) composed of oil, surfactant, and co‐surfactant for oral administration was formulated. The SEDDS formulations were optimized by evaluating their ability to self‐emulsifying when introduced to an aqueous medium under gentle agitation, and by determination of particle size of the resulting emulsion. Optimized formulation of SEDDS was selected for bioavailability assessment in rabbits. Also, the anti‐inflammatory effect of SEDDS formulation was determined in rats, compared with powder drug and etodolac suspension in water (50 mg kg−1).
The formation of melt dispersion is an effective method of increasing the dissolution rate of poo... more The formation of melt dispersion is an effective method of increasing the dissolution rate of poorly soluble drugs, and hence, of improving the bioavailability. The carrier fusion method was used to prepare different dispersion of etodolac using Gelucire 44/14 and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). The physical characteristics of the binary systems were determined by differential scanning calorimetry (DSC), infrared spectroscopy (IR). The release rate from the resulting dispersion was determined from dissolution studies by use of USP dissolution apparatus II (paddle method). The dissolution rate of etodolac is increased in all the dispersion systems compared to that of pure drug. A liquid dispersion system of etodolac (20%) and Gelucire 44/14: TPGS blend (80%), in different ratios, was also prepared. The capsule formulation was subjected to stability studies at different temperature and humidity conditions as per ICH guidelines. Physical and chemical properties of the dispersion didn&#39;t change during a period of storage at room temperature and at 4 degrees C, 0% RH. It was found that etodolac was chemically stable against the effects of temperature and humidity. However, the relative humidity and storage time exerted an effect on the dissolution behavior of etodolac. The changes in dissolution behavior after storage under conditions of high humidity and temperature might be related to the formation of etodolac microcrystal and to water absorption by the carrier during storage. It is predicted that acceptable shelf-lives should result when moisture-resistant packaging is used for pharmaceutical formulations of this type.
In view of the good skin tolerability, glycofurol was used as a vehicle-based gel, and its effect... more In view of the good skin tolerability, glycofurol was used as a vehicle-based gel, and its effect in the topical penetration of Naproxen (NAP) was investigated. The aims of this study were to develop a suitable gel with bioadhesive property, spreadability, and viscosity for topical anti-inflammatory effect. Three gelling and adhesive agents were examined: Carbopol 974P, Gantrez AN 119, and polyvinylpyrollidone K30. Skin permeation rates and lag times of NAP were evaluated using the Franz-type diffusion cell in order to optimize the gel formulation. The permeation rate of NAP-based gel across the excised rat skin was investigated. A significant increase in permeability parameters such as steady-state flux (J ss), permeability coefficient (K p), and penetration index (PI) was observed in optimized formulation containing 2% Transcutol as an permeation enhancer. From skin irritation test, it was concluded that the optimized novel glycofurol-based gel formulation was safe to be used for topical drug delivery. The developed glycofurol-based gel appeared promising for dermal and transdermal delivery of naproxen and could be applicable with water-insoluble drugs, which would circumvent most of the problems associated with drug therapy.
The aim of the present study was to investigate the potential of nanoemulsion formulations for tr... more The aim of the present study was to investigate the potential of nanoemulsion formulations for transdermal delivery of indomethacin (IND). Nanoemulsions formulations with different Surfactant: co surfactant ratios (S mix); F1-F6 (1:1, 2:2, 3:1, 4:1, 1:2 and 3:2) were prepared by the spontaneous emulsification method, and characterized for morphology using transmission electron microscopy (TEM), droplet size, and rheological characteristics. The ex vivo skin permeation studies were performed using Franz diffusion cell with rabbit skin as permeation membrane. A significant increase in the permeability parameters such as steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio (Er) was observed in nanoemulsion formulations compared with the conventional IND gel. The anti-inflammatory effects of nanoemulsion formulations showed a significant increase in percent inhibition value after 4 hours when compared with conventional IND gel on carrageenan-induced paw edema in rats. Significant increase in permeability parameters was observed in nanoemulsion formulations (P < 0.05). The steady-state flux (J ss) and permeability coefficient (K p) for optimized nanoemulsion formulation (F 1 , 1:1 S mix were found to be 22.61±3.45 μg/ cm 2 /h and 0.22x10 − 2 ±0.0003 cm/h, respectively), which were significant compared with conventional IND gel and (P < 0.001). Enhancement ratio (E r) was found to be 8.939 in optimized formulation F1 compared with IND gel. These results suggested that nanoemulsions can be used as potential vehicles for improved transdermal delivery of indomethacin as an approach to eliminate the side effect of the oral dose.
Objectives The objective of this study was to prepare a self-emulsifying drug delivery system (SE... more Objectives The objective of this study was to prepare a self-emulsifying drug delivery system (SEDDS) for oral bioavailability enhancement of a poorly water-soluble drug, etodolac. The SEDDS formulations were optimized by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation, and by determination of the particle size of the resulting emulsion. Methods An optimized formulation of SEDDS (composed of 20% etodolac, 30% oil Labrafac WL1349, 10% Lauroglycol 90 and 40% Labrasol) was selected for bioavailability assessment in rabbits. The anti-inflammatory effect was also determined in rats, and compared with powder drug and etodolac suspension in water (50 mg/kg). Key findings The peak plasma concentration of 16.4 ± 1.1 μg/ml appeared after 1.3 ± 0.2 h, whereas with powder drug and etodolac suspension the values were 7.5 ± 0.5 and 10.6 ± 0.7 μg/ml at 4.2 ± 0.4 and 2.4 ± 0.2 h, respectively. The AUC0–8 of the etodolac SEDDS formulation was 2.3...
The purpose of this study was to evaluate the bioavailability of locally produced 2.5 mg terbutal... more The purpose of this study was to evaluate the bioavailability of locally produced 2.5 mg terbutaline sulphate tablets (brand A ) relative to a reference product, Bricanyl 2.5 mg tablets (brand 6). The study was a single dose 5 mg randomized crossover one in 15 healthy volunteers in the fasting state. Urine was collected at intervals of 24 h. Total terbutaline excreted in urine as unchanged drug and as conjugates (sulphate and glucuronide) was determined by a developed and validated HPLC method. In-vitro characteristics of both brands were similar. Based on percent of the dose excreted in urine, the oral bioavailability ranged from 33.5% to 75.8% for both brands. Statistics were applied to judge bioequivalence according to USP 24 in-vivo bioequivalence guidance. Results indicated that brand A and B were bioequivalent and hence interchangeable in medical practice.
Journal of Drug Delivery Science and Technology, 2012
Liquisolid compacts of diltiazem hydrochloride (DTZ) were prepared using three different methods ... more Liquisolid compacts of diltiazem hydrochloride (DTZ) were prepared using three different methods to sustain the drug release rate. Ethyl cellulose, hydroxypropyl methylcellulose and Sterotex were used separately in this study as adjuvant in the first method of preparation and as carriers in the second method. These two methods involved the addition of the binary mixture of carrier-coating materials to the liquid medication in propylene glycol under continuous stirring. The third method of preparation involved the addition of the dispersed medication in Tween 20 to the binary mixture of carrier and coating materials. The final mixtures were then subjected to thermal analysis and flowability studies before compaction into tablets. DTZ tablets prepared by the liquisolid technique were subjected to dissolution rate studies to determine the release rate of the drug in comparison with the conventional tablets. Formulations containing HPMC prepared by the different techniques showed promising extended release of the drug, followed by formulations containing EC. Formulations containing Sterotex showed the least drug release-retardation effect. Release kinetic studies revealed that the release obeyed Higuchi's model.
The aim of this study was to formulate stable film-coated montelukast sodium (MS) tablets using O... more The aim of this study was to formulate stable film-coated montelukast sodium (MS) tablets using Opadry ® yellow 20A82938 (Montikast ® tablets) and to evaluate their in vitro and in vivo release profile. Methods: MS core tablets were manufactured using a direct compression method. Opadry yellow 20A82938 aqueous coating dispersion was used as the film-coating material. Dissolution of the film-coated tablets was tested in 900 mL of 0.5% sodium lauryl sulfate solution and the bioequivalence of the tablets was tested by comparing them with a reference formulation-Singulair ® tablets. In vitro-in vivo correlation was evaluated. The stability of the obtained film-coated tablets was evaluated according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines. Results: The efficiency of the film coating was determined by subjecting the coated tablets to gastric pH and drug release was analyzed using high-performance liquid chromatography. The coated tablets had no obvious defects. MS release met the study criterion of not less than 80% dissolved after 30 minutes in 0.5% sodium lauryl sulfate solution. Statistical comparison of the main pharmacokinetic parameters clearly indicated no significant difference between test and reference in any of the calculated pharmacokinetic parameters. Level A correlation between in vitro drug release and in vivo absorption was found to be satisfactory. Conclusion: These findings suggest that aqueous film coating with Opadry yellow 20A82938 is an easy, reproducible, and economical approach for preparing stable MS film-coated tablets without affecting the drug-release characteristics.
T he objective of the present study was to investigate the potential of microemulsion formulation... more T he objective of the present study was to investigate the potential of microemulsion formulations for transdermal delivery of indomethacin (IND). Microemulsion formulations with different surfactant:cosurfactant ratios (S mix); F1-F6 (1:1, 2:2, 3:1, 4:1, 1:2, and 3:2) were prepared by the spontaneous emulsification method, and characterized for morphology, droplet size, and rheological characteristics. The ex vivo skin permeation studies were performed using Franz diffusion cell with rabbit skin as a permeation membrane. A significant increase in the steady-state flux (J ss), permeability coefficient (K p), and enhancement ratio (E r) was observed in microemulsion formulations compared with the conventional IND gel. The antiinflammatory effects of microemulsion formulations showed a significant increase in percent edema inhibition value after 4 hours. The optimized formulation showed a significant increase in the steady-state flux (J ss) and permeability coefficient (K p). The enhancement ratio (E r) was found to be 8.939 in optimized formulation F1 compared with IND gel.
T he aim of the current study was to design oral controlled release (CR) theophylline anhydrous b... more T he aim of the current study was to design oral controlled release (CR) theophylline anhydrous bioadhesive tablets and to optimize the drug release profile and in vitro bioadhesion strength. Different types of natural hydrophilic polymers such as xanthun gum, locust bean gum, guar gum, karaya gum, and their combinations were used to formulate matrix tablets. Tablets of anhydrous theophylline were prepared by the direct compression method and were subjected to in vitro drug dissolution for 12 hours using the USP dissolution apparatus basket type at a speed of 100 rpm and temperature of 37 ± 0.5°C using gastric fluid (pH 1.2). The bioadhesive strength of the tablets was measured as the force of detachment against the porcine gastric mucosa. The in vitro release study as well as the retention time of the bioadhesive tablets on the mucous membrane were investigated to develop a bioadhesive polymer-based CR delivery system and to evaluate the performance of such a delivery device. The combination of karaya gum:guar gum (6:4) tablet showed a greater bioadhesive strength as compared with a single gum and other gum combination tablets. Karaya gum:guar gum-loaded tablets were not discharged from the mucous membrane and were dissolved in the gastric fluid. An increase in the gum concentration increases the drug release profile beyond 12 hours whereas there is no significant effect of gum concentration on the bioadhesive strength of the tablet.
The purpose of this study was to prepare a pressure-controlled colon delivery capsule (PCDC) cont... more The purpose of this study was to prepare a pressure-controlled colon delivery capsule (PCDC) containing theophylline (TPH) dispersion in a lipid matrix as a chronotherapeutic drug delivery system for the treatment of nocturnal asthma. The system was made by film coating using Eudragit S100- based formula over the sealed-hard gelatin capsules containing the drug-lipid dispersion. The lipid formula was composed mainly of Gelucire 33/01 (G33) with different ratios of surfactants (1-10%). The efficiency of the prepared system was evaluated in vitro for its ability to withstand both the gastric and intestinal medium. In addition, the drug plasma concentrations were monitored after single administration to Beagle dogs and compared to that obtained after administration of a reference marketed, generic, sustained-release TPH tablets, Avolen(®) SR. It was found that the optimum lipid formula was GL2 containing 90% G33 and 10% Labrasol. The film-coated capsules showed complete resistance to both the acidic environment (pH 1.2) for 2 hours and phosphate buffer pH 6.8 for 3 hours at 37°C. In vivo evaluation of the TPH-based PCDCs showed longer lag time compared TO the marketed formula followed by sudden increase in TPH blood levels, which recommends the high potential of this system as a chronotherapeutic drug delivery for nocturnal asthma. The prepared PCDCs exhibited a significantly higher C(max) and T(max) and a nonsignificantly different AUC compared with Avolen(®) SR. Higher TPH blood levels from 1 to 8 hours postadministration was detected in the case of the prepared PCDCs.
International Journal of Environmental Science & Technology, 2007
Desorption of Cu and low molecular weight dissolved organics are the primary factors that impact ... more Desorption of Cu and low molecular weight dissolved organics are the primary factors that impact fate and transport of Cu in soils. To improve predictions of the toxicity and threat from Cu contaminated soil, it is critical that time-dependent desorption behavior be understood. In this paper, the effect of organic ligands citrate, malate, and succinate on the kinetics of Cu desorption from contaminated soils varying widely in soil characteristics was investigated at 25 0 C and the soils used were referred to as clay, calcareous and sandy soils. The amount of Cu released by the used organic ligands varied greatly with physicochemical properties of the soils. The rate of Cu release by different extractants was in the order citric > malic > succinic, which was consistent with the stability constants of Cu complexes with these ligands. The modified Freundlich and the Elovich and Parabolic diffusion models were used to describe dsorption of Cu 2+ from the three studied soils as affected by the organic ligands. All of the models fit the data well with correlation coefficients ranging from 0.83 to 1.00 (P < 0.01). Each Model has a set of assumptions for the different physical and chemical properties of the systems to which they are being applied. The uses of these equations yield different magnitudes for the calculated variable, but the relationships between the soil + organic ligands and their effect (i.e., increase or decrease) on these variables are the same. Such information is critical, since Cu is used in a variety of industrial and manufacturing processes and is one of the most common contaminants found at hazardous waste sites.
Gliclazide (GLZ)-loaded microparticles made with a polymeric blend were prepared by a solvent eva... more Gliclazide (GLZ)-loaded microparticles made with a polymeric blend were prepared by a solvent evaporation technique. Organic solutions of two polymers, poly(ε-caprolactone) (PCL) and Eudragit RS (E RS) or ethyl cellulose (EC), in different weight ratios, and 33.3% of GLZ were prepared and dropped into aqueous solution of poly vinyl alcohol, in different experimental conditions, achieving drug-loaded microparticles. The obtained microparticles were characterized in terms of yield of production, shape, size, surface properties, drug content, and in vitro drug release behavior. The physical state of the drugs and the polymer was determined by scanning electron microscopy (SEM), Fourier transform infra red and differential scanning calorimetry. Following the in vitro release studies microparticles made from blends of polymer, PCL/E RS or EC showed slower drug release than microparticles made from single PCL polymer. Surface morphology also revealed presence of porous and spherical structure of microparticles. Microparticles showing sustained release of GLZ were examined in rabbits and plasma GLZ concentrations were calculated using HPLC method of assay.
Lipospheres of carbamazepine were prepared by melt dispersion technique using Precifac ATO 5 in t... more Lipospheres of carbamazepine were prepared by melt dispersion technique using Precifac ATO 5 in the various drug-lipid ratios. The resulting free-flowing lipospheres were evaluated with respect to surface morphology, particle size distribution, encapsulation efficiency, and in vitro release behavior. The effect of druglipid ratio, the surfactant added, emulsion stabilizer, and stirring speed also were identified as the key variables affecting the formation of discrete spherical lipospheres and drug release rate. The preparation conditions were optimized by using 0.4% w/v span 20 (Hydrophilic-Lipophilic Balance, HLB = 8.6) as a surfactant and 1% w/v gelatin solution as a stabilizer in presence of a high level of water. We found that the ratio of drug to lipid affects the size of the spheres. The incorporation efficiency was found to be high at all loadings. Increasing the lipid:drug ratio produced more spherical, smooth, and round lipospheres. All the prepared lipospheres exhibited slow release profiles dictating the Higuchi mode of release. We saw that the higher the sphere size and the ratio of Precifac, the slower is in vitro drug release.
Promising Pharmaceuticals 64 derivatives, allergenic patch tests and extracts, HIV and hepatitis ... more Promising Pharmaceuticals 64 derivatives, allergenic patch tests and extracts, HIV and hepatitis tests, gene therapy products, cells and tissues for transplantation, and new treatments for cancers, arthritis, and other serious diseases. CBER reviewed the first vaccines to immunize persons against infectious diseases, such as polio, pertussis ("whooping cough"), and German measles. CBER research led to important discoveries to safely collect, prepare, and transfuse blood and blood plasma. 2. Biological products, industry history (1) Biological products were created with biotechnology, the scientific and engineering procedures involved in manipulating organisms or biological components at the cellular, subcellular, or molecular level. These manipulations were carried out to make or modify plants and animals or other biological substances with desired traits. Although examples of primitive biotech processes dated back to ancient times (such as the use of fermentation in brewing and leavening agents in baking), their use in medical and pharmaceutical applications was an innovation of the latter decades of the twentieth century. Some analysts compared the biotech industry's impact on global medical care with the computer industry's impact on communication. Biotech researchers produced products in essentially three ways: by developing ways to achieve commercial production of naturally occurring substances; by genetically altering naturally occurring substances; and by creating entirely new substances. Some of the tools used by biotech researchers included recombinant DNA and monoclonal antibodies. Recombinant DNA involved the ability to take the deoxyribonucleic acid (DNA) from one organism and combine it with the DNA from another organism thereby creating new products and processes. By using recombinant DNA techniques researchers were able to select specific genes and introduce them into other cells or living organisms to create products with specific attributes. Monoclonal antibodies were developed from cultures of single cells using cloning techniques. They were designed for use in attacking toxins, viruses, and cancer cells. Because the biological products presented for approval often involved new technologies or innovative therapies for diseases that had not been previously treated successfully, the approval process frequently proved to be long and costly. Many companies struggled financially through the 1980s waiting for an FDA determination.
Gliclazide (GLZ)/Chitosan microparticles were prepared with tripolyphosphate (TPP) by ionic cross... more Gliclazide (GLZ)/Chitosan microparticles were prepared with tripolyphosphate (TPP) by ionic cross-linking. The particle sizes of TPP-chitosan microparticles were in the range 675-887 µm and the loading efficiencies of drug was more than 94.0%. Chitosan concentration, TPP solution pH and glutaraldehyde volume added to the TPP cross-linking solution had an effect on the drug release characteristics. The microparticles were examined with scanning electron microscopy and infrared spectroscopy. Furthermore, pectin can interact with cationic chitosan on the surface of these TPP/chitosan microparticles to form a polyelectrolyte complex film for the improvement of the drug sustained-release performances. In vivo testing of the GLZ-chitosan microparticles in diabetic albino rabbits demonstrated significant antidiabetic effect of GLZ/chitosan microparticles after 8 h which lasts for 18 h, compared with GLZ powder which produced maximum hypoglycaemic effect after 4 h, suggesting that GLZ/chitosan microparticles are a valuable system for the long-term delivery of GLZ.
European Journal of Pharmaceutics and Biopharmaceutics, 2009
IK312532), a long-acting VIP derivative, was proposed as potential drug candidate for the treatme... more IK312532), a long-acting VIP derivative, was proposed as potential drug candidate for the treatment of asthma/COPD. The present work is aimed to elucidate solutionstate stability of IK312532 and to develop further stabilized derivative with equipotent or higher biological functions. A stability study on IK312532 was carried out in solution state, and degradation mechanism was deduced by UPLC-MS and amino acid analyses. Three novel VIP derivatives were designed and chemically synthesized on the basis of stability data, being subjected to physicochemical and pharmacological characterization. Solution-state stability studies revealed the gradual degradation of IK312532, following pseudo-first-order kinetics. Chemical modification of IK312532, mainly position at 24, resulted in marked improvement of stability, although the chemical modification had no influence on the secondary structure, receptor binding, and activation of adenylate cyclase in rat lung cells. Novel derivatives also exhibited more potent neurite outgrowth in rat pheochromocytoma PC12 cells when compared to VIP and IK312532, possibly due to improved stability. Deamination of Asn at position 24 might be responsible for degradation of VIP derivative, and stability and chemical modification studies led us to the successful development of novel VIP derivatives with higher stability and biological functions.
Magnetic nanoparticles are attractive targets owing to their unique characteristics that are not ... more Magnetic nanoparticles are attractive targets owing to their unique characteristics that are not shared by bulk materials. Magnetic particles, ranging from nanometer-sized to 1 µm in size, are being used in an increasing number of medical applications. The important properties of magnetic particles for medical applications are nontoxicity, biocompatiblilty, injectability and high-level accumulation in the target tissue or organ. Magnetic nanoparticles modified with organic molecules have been widely used for biotechnological and biomedical applications as their properties can be magnetically controlled by applying an external magnetic field. They offer high potential for numerous biomedical applications, such as cell separation, automated DNA extraction, gene targeting, drug delivery, MRI and hyperthermia. When coated with, for example, an antibody, they can be applied in highly sensitive immunoassays or small substance recoveries. Furthermore, a novel application of magnetic nanopa...
Targeting the brain via nasal administration of drugs has been studied frequently over the last f... more Targeting the brain via nasal administration of drugs has been studied frequently over the last few years. In this study, a suitable gel formulation was designed to provide the absorption of a highly lipophilic drug through nasal mucosa. For this purpose, carbamazepine was chosen as the model drug. Hypromellose and Carbopol were used as mucoadhesive polymers in the formulation to increase the residence time of the gel on the mucosa. The objective of this study was to confirm the existence of a transport pathway for a drug (carbamazepine) to the brain directly from the nasal cavity, by comparing the concentration of drug in the brain after intranasal (i.n.), intravenous (i.v.), and oral (p.o.) administration. A statistically significant high level of the drug was found in the brain following intranasal administration compared with the intravenous and oral routes. These findings suggested the existence of a direct transport pathway for carbamazepine from the nasal cavity to the brain....
The aim of this study was to develop and characterize diclofenac sodium loaded-cellulose acetate ... more The aim of this study was to develop and characterize diclofenac sodium loaded-cellulose acetate butyrate microparticles in order to obtain a controlled-release system. The influence of the type of polymer, the volume and composition of the internal phase, drug loading, surfactant concentration and additive added on microparticles characteristics (particle size, encapsulation efficiency, surface morphology and in vitro release profiles) was studied to optimize the microparticles system. The resultant microparticles were evaluated for the recovery, average particle size, drug loading and incorporation efficiency. The microparticles exhibited good flowing nature and compressibility index when compared to pure drug. Dissolution rate of diclofenac sodium in phosphate buffer (pH 6.8) increased with increases in initial drug loading, surfactant concentration and addition of alcohol as co-solvent but decreased with increases in the concentration of additives such as Gantrez AN or Eudragit S100 in the internal phase. The dissolution data showed a Higuchi diffusion pattern for most of the formulations. About 56-81% reduction in ulcerogenic activity was observed with microparticles containing Eudragit S100 17-25%, based on total polymer concentration, when compared with pure diclofenac sodium.
The present study focuses on enhancement of the dissolution and oral absorption of poorly water‐s... more The present study focuses on enhancement of the dissolution and oral absorption of poorly water‐soluble etodolac. A self‐emulsifying drug delivery system (SEDDS) composed of oil, surfactant, and co‐surfactant for oral administration was formulated. The SEDDS formulations were optimized by evaluating their ability to self‐emulsifying when introduced to an aqueous medium under gentle agitation, and by determination of particle size of the resulting emulsion. Optimized formulation of SEDDS was selected for bioavailability assessment in rabbits. Also, the anti‐inflammatory effect of SEDDS formulation was determined in rats, compared with powder drug and etodolac suspension in water (50 mg kg−1).
The formation of melt dispersion is an effective method of increasing the dissolution rate of poo... more The formation of melt dispersion is an effective method of increasing the dissolution rate of poorly soluble drugs, and hence, of improving the bioavailability. The carrier fusion method was used to prepare different dispersion of etodolac using Gelucire 44/14 and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). The physical characteristics of the binary systems were determined by differential scanning calorimetry (DSC), infrared spectroscopy (IR). The release rate from the resulting dispersion was determined from dissolution studies by use of USP dissolution apparatus II (paddle method). The dissolution rate of etodolac is increased in all the dispersion systems compared to that of pure drug. A liquid dispersion system of etodolac (20%) and Gelucire 44/14: TPGS blend (80%), in different ratios, was also prepared. The capsule formulation was subjected to stability studies at different temperature and humidity conditions as per ICH guidelines. Physical and chemical properties of the dispersion didn&#39;t change during a period of storage at room temperature and at 4 degrees C, 0% RH. It was found that etodolac was chemically stable against the effects of temperature and humidity. However, the relative humidity and storage time exerted an effect on the dissolution behavior of etodolac. The changes in dissolution behavior after storage under conditions of high humidity and temperature might be related to the formation of etodolac microcrystal and to water absorption by the carrier during storage. It is predicted that acceptable shelf-lives should result when moisture-resistant packaging is used for pharmaceutical formulations of this type.
In view of the good skin tolerability, glycofurol was used as a vehicle-based gel, and its effect... more In view of the good skin tolerability, glycofurol was used as a vehicle-based gel, and its effect in the topical penetration of Naproxen (NAP) was investigated. The aims of this study were to develop a suitable gel with bioadhesive property, spreadability, and viscosity for topical anti-inflammatory effect. Three gelling and adhesive agents were examined: Carbopol 974P, Gantrez AN 119, and polyvinylpyrollidone K30. Skin permeation rates and lag times of NAP were evaluated using the Franz-type diffusion cell in order to optimize the gel formulation. The permeation rate of NAP-based gel across the excised rat skin was investigated. A significant increase in permeability parameters such as steady-state flux (J ss), permeability coefficient (K p), and penetration index (PI) was observed in optimized formulation containing 2% Transcutol as an permeation enhancer. From skin irritation test, it was concluded that the optimized novel glycofurol-based gel formulation was safe to be used for topical drug delivery. The developed glycofurol-based gel appeared promising for dermal and transdermal delivery of naproxen and could be applicable with water-insoluble drugs, which would circumvent most of the problems associated with drug therapy.
The aim of the present study was to investigate the potential of nanoemulsion formulations for tr... more The aim of the present study was to investigate the potential of nanoemulsion formulations for transdermal delivery of indomethacin (IND). Nanoemulsions formulations with different Surfactant: co surfactant ratios (S mix); F1-F6 (1:1, 2:2, 3:1, 4:1, 1:2 and 3:2) were prepared by the spontaneous emulsification method, and characterized for morphology using transmission electron microscopy (TEM), droplet size, and rheological characteristics. The ex vivo skin permeation studies were performed using Franz diffusion cell with rabbit skin as permeation membrane. A significant increase in the permeability parameters such as steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio (Er) was observed in nanoemulsion formulations compared with the conventional IND gel. The anti-inflammatory effects of nanoemulsion formulations showed a significant increase in percent inhibition value after 4 hours when compared with conventional IND gel on carrageenan-induced paw edema in rats. Significant increase in permeability parameters was observed in nanoemulsion formulations (P < 0.05). The steady-state flux (J ss) and permeability coefficient (K p) for optimized nanoemulsion formulation (F 1 , 1:1 S mix were found to be 22.61±3.45 μg/ cm 2 /h and 0.22x10 − 2 ±0.0003 cm/h, respectively), which were significant compared with conventional IND gel and (P < 0.001). Enhancement ratio (E r) was found to be 8.939 in optimized formulation F1 compared with IND gel. These results suggested that nanoemulsions can be used as potential vehicles for improved transdermal delivery of indomethacin as an approach to eliminate the side effect of the oral dose.
Objectives The objective of this study was to prepare a self-emulsifying drug delivery system (SE... more Objectives The objective of this study was to prepare a self-emulsifying drug delivery system (SEDDS) for oral bioavailability enhancement of a poorly water-soluble drug, etodolac. The SEDDS formulations were optimized by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation, and by determination of the particle size of the resulting emulsion. Methods An optimized formulation of SEDDS (composed of 20% etodolac, 30% oil Labrafac WL1349, 10% Lauroglycol 90 and 40% Labrasol) was selected for bioavailability assessment in rabbits. The anti-inflammatory effect was also determined in rats, and compared with powder drug and etodolac suspension in water (50 mg/kg). Key findings The peak plasma concentration of 16.4 ± 1.1 μg/ml appeared after 1.3 ± 0.2 h, whereas with powder drug and etodolac suspension the values were 7.5 ± 0.5 and 10.6 ± 0.7 μg/ml at 4.2 ± 0.4 and 2.4 ± 0.2 h, respectively. The AUC0–8 of the etodolac SEDDS formulation was 2.3...
Uploads
Papers by Nahla Barakat