Biomedical subjects

Mohammad Barzegar-Jalali

Publications and source records attributed to Mohammad Barzegar-Jalali.

11 recordsLinked to original sources

PubMed2007

Kinetic analysis of chlorpropamide dissolution from solid dispersions.

Solid dispersions (SDs) of chlorpropamide were prepared by the solvent deposition technique using two grades of microcrystalline cellulose as carrier materials with different ratios of drug to carrier. The dissolution rate of chlorpropmide from the SDs was carried out at two physiological pH values of 1.1 and 7.25 simulating gastric and intestinal environments. The dissolution was dependent on the grade, the ratio of drug to carrier and pH. The higher dissolution was observed for more hydrophilic grade of the carrier as well as the higher ratio of carrier to drug. At the higher pH the drug dissolved much faster than the lower pH. X-ray diffraction showed some reduced drug crystallinity in SDs whereas infrared spectroscopy revealed no drug interactions with solvent and the carriers. The enhanced dissolution was attributed to the reduced drug crystallinity, decreased particle size, increased wettability and reduced aggregation of the hydrophobic drug particles. A novel model denoted as reciprocal powered time model with its theoretical justification was employed to analyze the dissolution data and proved to be superior to commonly used models for the analysis of the data. There was a quantitative relation between the model parameter and the ratio of carrier to drug which could be of value in dissolution rate prediction.

Chlorpropamide↗

PubMed2007

Preparation and characterization of solid dispersions of piroxicam with hydrophilic carriers.

The objective of this study was to improve the dissolution rate of a poor water soluble drug, piroxicam, by solid dispersion technique. Solid dispersions were prepared by three different methods depending on the type of carrier. The dissolution rate of piroxicam was markedly increased in solid dispersion of myrj 52, Eudragit E100 and mannitol. Solubility studies revealed a marked increase in the solubility of piroxicam with an increase in myrj 52 and Eudragit E100 concentrations. Data from the X-ray diffraction and FT-IR spectroscopy showed that piroxicam was amorphous in the solid dispersions prepared with dextrin and Eudragit E100.

Acrylates↗

PubMed2006

QSPR models for the prediction of apparent volume of distribution.

An estimate of volume of distribution (V(d)) is of paramount importance both in drug choice as well as maintenance and loading dose calculations in therapeutics. It can also be used in the prediction of drug biological half life. This study employs quantitative structure-pharmacokinetic relationship (QSPR) techniques for the prediction of volume of distribution. Values of V(d) for 129 drugs were collated from the literature. Structural descriptors consisted of partitioning, quantum mechanical, molecular mechanical, and connectivity parameters calculated by specialized software and pK(a) values obtained from ACD labs/log D database. Genetic algorithm and stepwise regression analyses were used for variable selection and model development. Models were validated using a leave-many-out procedure. QSPR analyses resulted in a number of significant models for acidic and basic drugs separately, and for all the drugs. Validation studies showed that mean fold error of predictions for the selected models were between 1.79 and 2.17. Although separate QSPR models for acids and bases resulted in lower prediction errors than models for all the drugs, the external validation study showed a limited applicability for the equation obtained for acids. Therefore, the universal model that requires only calculated structural descriptors was recommended. The QSPR model is able to predict the volume of distribution of drugs belonging to different chemical classes with a prediction error similar to that of the other more complicated prediction methods including the commonly practiced interspecies scaling. The structural descriptors in the model can be interpreted based on the known mechanisms of distribution and the molecular structures of the drugs.

Algorithms↗

PubMed2006

A new solution for a chronic problem; aqueous enteric coating.

In this research, we have reconsidered the current enteric coating techniques and offered a new solution using both theoretical and practical approaches. This approach is based on the fact that salt formation can solubilize the pH-sensitive polymers in water. However, having applied the polymer solution onto the dosage form's surface, the polymer should be converted to the nonionized form for delayed release action. Ammonium hydrogen carbonate (AHC) is used as a buffering agent with dual actions of salting in and desalting the polymer. Following the application of the coating medium onto the dosage form's surface and drying, AHC dissociate completely to ammonia, carbon dioxide, and water converting the polymer to its nonionized form. FT-IR studies on free film samples further confirmed the proposed mechanism. A range of pH-sensitive polymers and other ingredients in water have been successfully applied at the surface of a model ASA tablets, using pan coating technique. According to the SEM observation, the coating layer is very dense and rigid, despite the fact that, the coated amount of the polymers is quit small. The enteric tablets maintain their shapes in acid medium and passed the USP dissolution test for DR ASA tablets.

Aspirin↗

PubMed2006

Evaluation of in vitro-in vivo correlation and anticonvulsive effect of carbamazepine after cogrinding with microcrystalline cellulose.

PURPOSE: Carbamazepine is a poor water soluble drug and its bioavailability is limited by dissolution rate. Dissolution, serum concentration and anticonvulsive effect of the drug have been evaluated after cogrinding with microcrystalline cellulose. A cogrinding technique was used to increase the dissolution, serum concentrations and anticonvulsive effect of the drug. A novel deconvolution technique of in vitro in vivo correlation was evaluated. METHODS: The drug coground with microcrystalline cellulose, the corresponding physical mixture, unground and ground drug powder were subjected to dissolution measurement. Coground and unground drug serum concentrations were investigated in rabbits. Also the anticonvulsive effects of the latter preparations were assessed in mice. For elucidation of observed in vitro and in vivo differences FT-IR spectroscopy, X-ray diffraction patterns and DSC thermograms of the preparations were studied. RESULTS: The dissolution of the coground was the highest (percent dissolved in the first 20 minutes, %D20', was 97.5). The unground drug powder exhibited the lowest dissolution (%D20'=40). The difference was reflected in their corresponding area under the mean serum concentration curves between 0-16 hr (118.96 vs 54.17 microg x hr/ml) as well as protection abilities against strychnine and electrically induced seizures. The onset of tonic seizures induced by strychnine was increased between 40-140% in the case of the coground system depending on dose and time of carbamazepine administration. CONCLUSION: Cogrinding was an effective technique in increasing carbamazepine dissolution due to reduced crystallinity as seen in X-ray pattern, enhanced wettability and decreased particle size, which in turn resulted in increased serum concentrations and its anticonvulsive effect. A novel simple deconvolusion technique not requiring intravenous data denoted as the double reciprocal area method was used to establish correlation between in vitro and in vivo parameters.

Animals↗

PubMed2005

Design and evaluation of 1- and 3-layer matrices of verapamil hydrochloride for sustaining its release.

The present study was performed to design oral controlled delivery systems for the water-soluble drug, verapamil hydrochloride, using natural and semisynthetic polymers as carriers in the forms of 1- and 3-layer matrix tablets. Verapamil hydrochloride 1-layer matrix tablets containing hydroxypropylmethylcellulose, tragacanth, and acacia either alone or mixed were prepared by direct compression technique. 3-layer matrix tablets were prepared by compressing the polymers as release retardant layers on both sides of the core containing the drug. The prepared tablets were subjected to in vitro drug release studies. Tragacanth when used as the carrier in the formulation of 1- and 3-layer matrices produced satisfactory release prolongation either alone or in combination with the other 2 polymers. On the other hand, acacia did not show enough prolonging efficiency in 1- and 3-layer matrix tablets. The results also showed that the location of the polymers in the 3-layer tablets has a pronounced effect on the drug release. Kinetic analysis of drug release from matrices exhibiting sustained release indicated that release was predominantly attributable to the contribution made by Fickian diffusion, while the erosion/relaxation mechanisms had a minor role in the release.

Chemistry, Pharmaceutical↗

PubMed2005

Simultaneous determination of naproxen, ketoprofen and phenol red in samples from rat intestinal permeability studies: HPLC method development and validation.

A simple reversed-phase high performance liquid chromatographic method with UV detection at 270 nm was developed for simultaneous quantitation of ketoprofen and naproxen sodium along with phenol red as a non-absorbable marker for in situ permeability studies. The mobile phase was a mixture of 20% methanol, 28% of acetonitrile, 52% water and 0.4 ml triethylamine (adjusted to pH 3.2 using orthophosphoric acid). Analysis was run at a flow of 1.5 ml/min with a 20 min run time. The calibration curves were linear for all three compounds (r>0.999) across the concentration range of 15.6-250 microg/ml with a limit of quantitation of 0.3, 0.25 and 0.2 ng/ml for naproxen, ketoprofen and phenol red, respectively. The coefficient of variation for intra-assay and inter-assay precision was less than or equal to 5.3% and the accuracy was between 95.36 and 101.6%. Using the SPIP technique and the suggested HPLC method for sample analysis, the mean values of 1.17e(-4) (+/-0.28) cm/s and 0.97e(-4) (+/-0.2) cm/s were obtained for naproxen and ketoprofen, respectively.

Acetonitriles↗

PubMed2005

Enhancing dissolution, serum concentrations and hypoglycemic effect of glibenclamide using solvent deposition technique.

PURPOSE: Glibenclamide is practically insoluble in water and its GI absorption is limited by its dissolution rate. Therefore, to enhance the drug dissolution, serum concentrations and its hypoglycemic effects, it was formulated as solid dispersions and evaluated the relevant in vitro and in vivo parameters. METHODS: The drug solid dispersions were prepared by solvent deposition technique using microcrystalline cellulose as the carrier in different ratios and their dissolution rates were compared to those of pure drug and its physical mixture with carrier. Drug serum concentrations and hypoglycemic effects in rabbits of pure drug, a physical mixture and the corresponding solid dispersion were investigated. In order to elucidate the observed in vitro and in vivo differences, IR spectroscopy and x-ray diffraction patterns of the formulations were studied. RESULTS: The solid dispersion with the drug to carrier ratio of 1:19 showed the highest dissolution rate with the dissolution efficiency (DE) of 44.42 in comparison to pure drug (DE = 3.82), physical mixture (DE = 4.91) and other solid dispersions (DE between 13.85-39.94) and also produced higher drug serum concentrations (more than 4 times at 6th hour post dose) as well as enhanced hypoglycemic effects relative to pure drug and its corresponding physical mixture. CONCLUSIONS: Solvent deposition technique was proved an effective tool of increasing dissolution probably due to enhanced wettability and reduced drug particle size, which in turn led to enhance drug serum concentrations and its hypoglycemic effects. Strong quantitative correlations were established between dissolution parameter and parameters related to serum concentrations as well as hypoglycemic effects.

Animals↗

PubMed2005

The effect of type and concentration of vehicles on the dissolution rate of a poorly soluble drug (indomethacin) from liquisolid compacts.

PURPOSE: For poorly soluble, highly permeable (Class II) drugs, such as indomethacin, the rate of oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Therefore together with the permeability, the solubility and dissolution behaviour of a drug are key determinants of its oral bioavailability. The object of the present study is to increase dissolution rate of indomethacin using liquisolid compacts. METHODS: Several formulations of liquisolid compacts containing various ratios of drug: propylene glycol (ranging from 1:1 to 1:4) was prepared. In this study the ratio of microcrystalline cellulose (carrier) to silica (coating powder material) was 20 in all formulations. The dissolution behaviour of indomethacin from liquisolid compacts and conventional formulations was investigated at different pHs (1.2 and 7.2). RESULTS: The results showed that liquisolid compacts demonstrated considerably higher drug dissolution rates than those of conventionally made capsules and directly compressed tablets containing indomethacin. This was due to increased wetting properties and surface of drug available for dissolution. Also it has been shown that the fraction of molecularly dispersed drug (FM) in the liquid medication of liquisolid systems was directly proportional to their indomethacin dissolution rates (DR). An attempt was made to correlate the percentage drug dissolved in 10-min with the solubility of indomethacin in different vehicles. A plot of the percentage drug dissolved against the solubility of indomethacin showed that the amount of drug dissolved increased linearly (correlation coefficient of 0.9994 and 0.996 at pH 7.2 and 1.2 respectively) with an increase in solubility of indomethacin in the vehicles. CONCLUSION: The liquisolid compacts technique can be a promising alternative for the formulation of water insoluble drugs, such as indomethacin into rapid release tablets.

Chemistry, Pharmaceutical↗

PubMed2004

Quantitative structure-pharmacokinetic relationship modelling: apparent volume of distribution.

The purpose of this study was to develop a quantitative structure-activity relationship (QSAR) for the prediction of the apparent volume of distribution (Vd) in man for a heterogeneous series of drugs. The relationship of many computed, and some experimental, structural descriptors with Vd, and the Vd corrected for protein binding (unbound Vd), was investigated. Models were constructed using stepwise regression analysis for all the 70 drugs in the dataset, as well as for acidic drugs and basic drugs separately. The predictive power of the models was assessed using half the chemicals as a test set, and revealed that the models for Vd yielded lower prediction errors than those constructed for the unbound Vd (mean fold error of 2.01 for Vd compared with 2.28 for unbound Vd). Moreover, the separation of the compounds into acids and bases did not reduce the prediction error significantly.

Algorithms↗

PubMed2002

Theoretical modeling of oral absorption of barbiturates.

The structural characteristics governing gastric absorption of barbiturates were studied using QSAR methodology. The results showed that the gastric absorption rate constant could be modeled using the theoretical parameters, accessible surface area, atomic charges and electrostatic potentials. Using molecular connectivity indexes was also satisfactory in modeling the absorption.

Absorption↗