Ali Nokhodchi

Piroxicam nanoparticles for ocular delivery: Physicochemical characterization and implementation in endotoxin-induced uveitis

To investigate the anti-inflammatory impacts of piroxicam nanosuspension, in the current investigation, piroxicam:Eudragit®RS100 nanoformulations were used to control inflammatory symptoms in the rabbits with endotoxin-induced uveitis (EIU). The nanoparticles of piroxicam:Eudragit®RS100 was formulated using the solvent evaporation/extraction technique. The morphological and physicochemical characteristics of nanoparticles were studied using particle size analysis, X-ray crystallography, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). Drug release profiles were examined by fitting the data to the most common kinetic models. Selected nanosuspensions were used to assess the anti-inflammatory impacts of piroxicam nanoparticles in the rabbits with EIU. The major symptoms of EIU (i.e. inflammation and leukocytes numbers in the aqueous humor) were examined. All the prepared piroxicam formulations using Eudragit®RS100 resulted in a nano-range size particles and displayed spherical smooth morphology with positively charged surface, however, the formulated particles of drug alone using same methodology failed to manifest such characteristics. The Eudragit®RS100 containing nanoparticles displayed lower crystallinity than piroxicam with no chemical interactions between the drug and polymer molecules. Kinetically, the release profiles of piroxicam from nanoparticles appeared to fit best with the Weibull model and diffusion was the superior phenomenon. The in vivo examinations revealed that the inflammation can be inhibited by the drug:polymer nanosuspension more significantly than the microsuspension of drug alone in the rabbits with EIU. Upon these findings, we propose that the piroxicam:Eudragit®RS100 nanosuspensions may be considered as an improved ocular delivery system for locally inhibition of inflammation.

The enhancement effect of surfactants on the penetration of lorazepam through rat skin

Lorazepam is an anxiolytic, antidepressant agent, having suitable feature for transdermal delivery. The percutaneous permeation of lorazepam was investigated in rat skin after application of a water:propylene glycol (50:50%v/v). The enhancing effects of various surfactants (sodium lauryl sulfate (SLS), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride or Tween 80) with different concentrations on the permeation of lorazepam were evaluated using Franz diffusion cells fitted with rat skins. Flux, K(p), lag time and enhancement ratios (ERs) of lorazepam were measured over 24 h and compared with control sample. Furthermore, lorazepam solubility in presence of surfactants was determined. The in vitro permeation experiments with rat skin revealed that the surfactant enhancers varied in their ability to enhance the flux of lorazepam. The permeation profile of lorazepam in presence of the cationic surfactant, CTAB, reveals that an increase in the concentration of CTAB results in an increase in the flux of lorazepam in comparison with the control. But an increase in concentration of CTAB or benzalkounium chloride from 0.5 to 1% w/w or from 1 to 2.5% w/w resulted in a reduction in ER, respectively. Benzalkonium chloride which possessed the highest lipophilicity (logP=1.9) among cationic surfactants provided the greatest enhancement for lorazepam flux (7.66-fold over control) at 1% w/w of the surfactant. CTAB (logP<1) and sodium lauryl sulphate at a concentration of 5% w/w (the highest concentration) exhibited the greatest increase in flux of lorazepam compared with control (9.82 and 11.30-fold, respectively, over control). This is attributed to the damaging effect of the cationic and anionic surfactants on the skin at higher concentration. The results also showed that the highest ER was obtained in presence of 1% w/w surfactant with the exception of SLS and CTAB. The increase in flux at low enhancer concentrations is normally attributed to the ability of the surfactant molecules to penetrate the skin and increase its permeability. Reduction in the rate of transport of the drug present in enhancer systems beyond 1% w/w is attributed to the ability of the surfactant molecules to form micelles and is normally observed only if interaction between micelle and the drug occurs.

The effect of surfactants on the skin penetration of diazepam

The percutaneous permeation of diazepam was investigated in rat skin after application of a water-propylene glycol (50:50% v/v) using a diffusion cell technique. The effect of various surfactants (sodium lauryl sulfate (SLS), cetyltrimethylammonium bromide (CTAB), benzalkonium chloride or Tween 80) with different concentrations on skin permeability were evaluated. Flux, K(p), lag time and enhancement ratios (ERs) of diazepam were measured over 10 h and compared with control sample (containing no surfactant). Furthermore, diazepam solubility in presence of surfactants was determined. The in vitro permeation experiments with rat skin revealed that the surfactant enhancers varied in their ability to enhance the flux of diazepam. Benzalkonium chloride which possessed the highest lipophilicity (logP=1.9) among cationic surfactants provided the greatest enhancement for diazepam flux (7.98-fold over control). CTAB (logP<1) at a concentration of 1% w/w exhibited no significant increase in flux of diazepam compared to control (1.16-fold over control). The results also showed that the highest ER was obtained in presence of 1% w/w surfactant with the exception of SLS and CTAB. The increase in flux at low enhancer concentrations is normally attributed to the ability of the surfactant molecules to penetrate the skin and increase its permeability. Reduction in the rate of transport of the drug present in enhancer systems beyond 1% w/w is attributed to the ability of the surfactant to form micelles and is normally observed only if interaction between micelle and the drug occurs. The results showed that the nature of enhancer greatly influences cutaneous barrier impairment.

Physicochemical Characterization of Solid Dispersions of Indomethacin with PEG 6000, Myrj 52, Lactose, Sorbitol, Dextrin, and Eudragit® E100

The purpose of this study was to prepare and characterize solid dispersions of indomethacin with polyethylene glycol (PEG) 6000, Myrj 52, Eudragit® E100, and different carbohydrates such as lactose, mannitol, sorbitol, and dextrin. Indomethacin is a class II substance according to the Biopharmaceutics Classification System. It is a poorly water soluble antirheumatic agent. The goal was to investigate whether the solid dispersion can improve the dissolution properties of indomethacin. The solid dispersions were prepared by three different methods depending on the type of carrier. The evaluation of the properties of the dispersions was performed using solubility measurements, dissolution studies, Fourier‐transform infrared spectroscopy, and x‐ray powder diffractometery. The results indicate that lactose, mannitol, sorbitol, and especially Myrj 52 are suitable carriers to enhance the in vitro dissolution rate of indomethacin at pH 7.2. Eudragit E100, Myrj 52, and mannitol increase the dissolution properties at pH 1.2. The data from the x‐ray diffraction showed that the drug was still detectable in its solid state in all solid dispersions except solid dispersions with dextrin and high amounts of mannitol. However, the results from infrared spectroscopy together with those from x‐ray diffraction showed well‐defined drug–carrier interactions for dextrin coevaporates.

Crystal modification of phenytoin using different solvents and crystallization conditions

Phenytoin crystals having different types of habits, were prepared by recrystallization from ethanol and acetone solutions under different conditions (cooling rate or crystallization temperature, solvent evaporation and watering-out techniques). Scanning electron microscopy, X-ray powder diffractometry, FT-IR spectrometry and differential scanning calorimetry were used to investigate the physical characteristics of the crystals. The dissolution behavior and compaction properties of various batches of crystals were also studied. It was found that using watering-out technique as a crystallization method, produced thin plate crystals, while the crystals obtained by other methods were needle shape for alcoholic solutions and rhombic for acetone solutions. X-ray diffraction spectra and differential scanning calorimetry studies, did not show any polymorphic change. The dissolution rate of different crystals was lower than that of untreated samples. The compacts of phenytoin crystals produced from alcohol or acetone (especially those made by watering-out method) had higher crushing strengths than untreated phenytoin compacts due to the lower porosity and the lower elastic recovery.

Liquisolid technique as a new approach to sustain propranolol hydrochloride release from tablet matrices

It is suggested here that liquisolid technique has the potential to be optimized for the reduction of drug dissolution rate and thereby production of sustained release systems. In the present study, propranolol hydrochloride was dispersed in polysorbate 80 as the liquid vehicle. Then a binary mixture of carrier-coating materials (Eudragit RL or RS as the carrier and silica as the coating material) was added to the liquid medication under continuous mixing in a mortar. The final mixture was compressed using the manual tableting machine. The effect of drug concentration, loading factor, thermal treating and aging on release profile of propranolol hydrochloride from liquisolid compacts were investigated at two pH values (1.2 and 6.8). The release rate of propranolol HCl from liquisolid compacts was compared to the release of propranolol HCl from conventional tablets. X-ray crystallography and DSC were used to investigate the formation of any complex between drug and excipients or any crystallinity changes during the manufacturing process. Propranolol HCl tablets prepared by liquisolid technique showed greater retardation properties in comparison with conventional matrix tablets. This investigation provided evidence that polysorbate 80 (Tween 80) has important role in sustaining the release of drug from liquisolid matrices, and a reduction of T(g) of the polymer can be the reason for the release prolongation of liquisolid tablets. The results also showed that wet granulation had remarkable impact on release rate of propranolol HCl from liquisolid compacts, reducing the release rate of drug from liquisolid compacts. The results showed that aging (liquisolid tablets were kept at 25 degrees C/75% relative humidity for 6 months) had no effect on hardness and dissolution profile of drug. The kinetics studies revealed that most of the liquisolid formulations followed the zero-order release pattern. X-ray crystallography and DSC ruled out any changes in crystallinity or complex formation during the manufacturing process of liquisolid formulations.

The effect of terpene concentrations on the skin penetration of diclofenac sodium.

Terpenes and sesquiterpenes have been suggested as promising non-toxic, non-irritating transdermal penetration enhancers. This investigation aimed to study the effect of terpene concentration on the transdermal absorption of diclofenac sodium from ethanol:glycerin:phosphate buffer solution (60:10:30). Therefore, enhancing effects of various terpenes (menthone, limonenoxide, carvone, nerolidol and farnsol) with different concentrations (0.25, 0.5, 1, 1.5 and 2.5%, v/v) on the permeation of diclofenac sodium were evaluated using Franz diffusion cells fitted with rat skin. Furthermore, solubility of diclofenac sodium in the vehicle in presence of different concentrations of terpenes was determined. The results showed that despite the negligible effect of terpenes on the drug solubility, there was a profound skin penetration enhancement effect, although the terpene enhancers varied in their ability to enhance the flux of diclofenac sodium. The results showed that at the highest concentration of terpene (2.5%, v/v) the rank order of enhancement effect for diclofenac sodium was nerolidol>farnesol>carvone>methone>limonenoxide, whereas at the low concentration of 0.25% the rank order was farnesol>carvone>nerolidol>menthone>limonenoxide. No direct relationship existed between terpene concentration and the permeation rate. The most outstanding penetration enhancer was nerolidol, providing an almost 198-fold increase in permeability coefficient of diclofenac sodium, followed by farnesol with a 78-fold increase.

Physicochemical and anti-bacterial performance characterization of clarithromycin nanoparticles as colloidal drug delivery system

The objective of the present study was to prepare clarithromycin (CLR) loaded biodegradable nanoparticles (NPS), with a view to investigate its physicochemical properties and anti-bacterial activity. PLGA was used as a biodegradable polymer and the particles were prepared by nano-precipitation method in 3 different drugs to polymer ratios. Evaluation of the physicochemical properties of the prepared nanoparticles was performed using encapsulation efficiency, nanoparticle production yield, dissolution studies, particle size analysis, zeta potential determination, differential scanning calorimetry, Fourier-transform infrared spectroscopy and X-ray powder diffractometry. The antimicrobial activity against Staphylococcus aureus was determined using serial dilution technique to achieve the minimum inhibitory concentration (MIC) of NPs. The particles were between 189 and 280 nm in size with narrow size distribution, spherical shape and 57.4-80.2% entrapment efficiency. Zeta potential of the NPs was fairly negative. The DSC thermograms and X-ray diffraction patterns revealed reduced drug crystallinity in the NPs. FT-IR spectroscopy demonstrated possible noncovalent interactions between the drug and polymer. In vitro release study showed an initial burst followed by a plateau during a period of 24h. The NPs were more effective than intact CLR against S. aureus so that the former showed equal antibacterial effect at 1/8 concentration of the intact drug. In conclusion, the prepared CLR nanoparticles are more potent against S. aureus with improved MICs and appropriate physicochemical properties that may be useful for other susceptible microorganisms and could be an appropriate candidate for intravenous, ocular and oral and topical preparations.

Development of azithromycin-PLGA nanoparticles: physicochemical characterization and antibacterial effect against Salmonella typhi

The objective of the present research was to formulate poly(lactide-co-glycolide) nanoparticles loaded with azithromycin with appropriate physicochemical properties and antimicrobial activity. Azithromycin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) were prepared in three different ratios of drug to polymer by nanoprecipitation technique. Antibacterial activity of these nanoparticles was examined against gram-negative intra cellular microorganism Salmonella typhi. The antibacterial effect was investigated using serial dilution technique to achieve the minimum inhibitory concentration (MIC) of nanoparticles. The results showed that physicochemical properties were affected by drug to polymer ratio. The results showed that nanoscale size particles ranging from 212 to 252nm were achieved. Physicochemical properties were affected by drug to polymer ratio. The highest entrapment efficiency (78.5+/-4.2%) was obtained when the ratio of drug to polymer was 1:3. Zeta (zeta) potential of the nanoparticles was fairly negative. The DSC thermograms and X-ray diffraction patterns revealed that the drug in the nanoparticles was in amorphous state. FT-IR spectroscopy demonstrated no detectable interactions between the drug and polymer in molecular level. In vitro release study showed two phases: an initial burst for 4h followed by a very slow release pattern during a period of 24h. The results of antimicrobial activity test showed that the nanoparticles were more effective than pure azithromycin against S. typhi with the nanoparticles showing equal antibacterial effect at 1/8 concentration of the intact drug. In conclusion, the azithromycin nanoparticle preparations showed appropriate physicochemical and improved antimicrobial properties which can be useful for oral administration.

To enhance dissolution rate of poorly water-soluble drugs: Glucosamine hydrochloride as a potential carrier in solid dispersion formulations

The solid dispersion technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs, however this is reliant on a suitable carrier and solvent being selected. The work presented explores D-glucosamine HCl (G-HCl) as a potential hydrophilic carrier to improve dissolution rate of a poorly water-soluble drug, carbamazepine (CBZ), from physical mixtures and solid dispersion formulations. The effect of different solvents in the preparation of solid dispersion formulations was also investigated. Solid dispersions of the drug and G-HCl were prepared using different ratios by the conventional solvent evaporation method. Different solvents (ethanol, acetone and water) were used as second variable in the preparation of solid dispersions. Physical mixtures of CBZ and G-HCl were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, FT-IR, SEM and DSC. These results showed that the presence of glucosamine can increase dissolution rate of CBZ compared to pure CBZ. All solid dispersions of CBZ-G-HCl showed considerably a higher dissolution rate than the corresponding physical mixtures. The presence of water during preparation of the solid dispersions reduced the dissolution rate of CBZ due to formation of carbamazepine dihydrate during the preparation of solid dispersion, as proved by DSC and FT-IR studies. To facilitate comparison, the dissolution efficiency was calculated for solid dispersions prepared with different solvents and the dissolution efficiency can generally be ranked as follows: ethanol>acetone>ethanol-water>acetone-water when the ratios of drug to carrier were 4:1 and 2:1. It has thus been shown that the use of G-HCl in solid dispersion formulations can significantly enhance the dissolution rate of poorly water-soluble drugs such as carbamazepine. This amino sugar could be used as a new carrier in solid dispersion formulations and would have significant commercial potential.