Effect of Silver Nanoparticles of Herbal Origin on the Compressive and Push-out Bond Strengths of Mineral Trioxide Aggregate.

Introduction: The purpose of this in vitro study was to investigate the effect of incorporating silver nanoparticles (AgNPs) of herbal origin into mineral trioxide aggregate (MTA) on the push-out bond strength (PBS) and compressive strength (CS) in simulated furcal area perforations. Materials and Methods: In this in vitro study, simulated furcal area perforations (1.3 mm in diameter and 2 mm in depth) were created in 40 extracted human lower molar teeth, which were divided into two groups (n=20): MTA alone and MTA combined with AgNPs (2% wt). Using a universal testing machine, PBS was evaluated by performing push-out tests, while CS was assessed using cylindrical specimens. The normal distribution of data was checked using the Kolmogorov-Smirnov test, and statistical analysis was performed using two-way ANOVA. Results: The CS results showed no significant difference between the MTA group at 4 and 21 days (P=0.297), but a significant difference was observed in the nanosilver/MTA group (P=0.013). However, there was no significant difference in the push-out bond strength among the study groups (P>0.05). Conclusion: The incorporation of herbal origin silver nanoparticles did not significantly affect the PBS or CS of MTA.

Osteogenesis Promotion of Selenium-Doped Hydroxyapatite for Application as Bone Scaffold.

The combined bioceramic of selenium (Se) and hydroxyapatite (HA) has been considered as a moderate bone scaffold biomaterial. In the present work, Se was doped into the HA structure using the mechano-chemical alloying (MCA) method for the improvement of osteogenic properties of HA. HA extracted from fish bone and Se-doped hydroxyapatite (Se-HA) were analyzed using X-ray diffraction spectra (XRD), scanning electron microscope (SEM), energy dispersion X-ray spectrometer (EDX), and Fourier transform infrared spectroscopy (FT-IR). In-vitro cell responses on the Se-HA bioceramic scaffold were investigated using human adipose-derived mesenchymal stem cells (hAD-MSCs). The effect of Se on cell proliferation was studied by MTT assay, and cell adhesion responses were analyzed by optical microscopy and SEM. Furthermore, the effect of Se on osteogenic properties of HA was studied by alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and Western blot tests. The MTT results showed that the Se dopant synergistically increases the proliferation of hAD-MSCs. Moreover, good cell-adhesive and osteoblast-shaped behaviors were observed on the Se-HA scaffold. The results of osteogenic differentiation demonstrated synergistically enhanced ALP activity and calcification on the Se dopant compared to HA. Also, the results of Western blot test presented that the differentiation of hAD-MSCs toward being a bone tissue was increased by up to 50% while selenium doping. Additional MTT analysis using Human Bone Osteosarcoma cell line (KHOS-240S) revealed the antiproliferative activity of the Se-HA scaffold against bone cancerous cells. Therefore, it has been concluded that Se-HA bioceramic can be employed as a scaffold with simultaneous anticancer and bone regenerative properties.

Enhancement of ketoconazole dissolution rate by the liquisolid technique.

The study was conducted to enhance the dissolution rate of ketoconazole (KCZ) (a poorly water-soluble drug) using the liquisolid technique. Microcrystalline cellulose, colloidal silica, PEG400 and polyvinyl pyrrolidone (PVP) were employed as a carrier, coating substance, nonvolatile solvent and additive in the KCZ liquisolid compact formulation, respectively. The drug-to-PEG400 and carrier-to-coating ratio variations, PVP concentration and aging effects on the in vitro release behavior were assessed. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) data revealed no alterations in the crystalline form of the drug and the KCZ-excipient interactions within the process. The load factor and the drug release rate were significantly enhanced compared to directly compressed tablets in the presence of the additive. Increasing the PEG400-to-drug ratio in liquid medications enhanced the dissolution rate remarkably. The dissolution profile and hardness of liquisolid compacts were not significantly altered by keeping the tablets at 40 °C and relative humidity of 75 % for 6 months. With the proposed modification of the liquisolid process, it is possible to obtain flowable, compactible liquisolid powders of high-dose poorly-water soluble drugs with an enhanced dissolution rate.

Morphological and physicochemical evaluation of the propranolol HCl-Eudragit® RS100 electrosprayed nanoformulations.

The aim of this study was to fabricate propranolol hydrochloride (Prop. HCl) (as a water-soluble drug):Eudragit® RS100 (Eud) nanobeads and nanofibres applying the electrospraying method as an economical and one-step technique. Different ratios of Prop. HCl:Eud (i.e. 1:5 and 1:10) at total solution concentrations of 10-20% W/V were investigated. The FE-SEM studies revealed that morphology and size of the samples were highly affected by the solution concentration; so that, the nanobeads (a mean diameter of 82.9 nm) were formed in low concentration and at the highest concentration of the solution, nanofibres (a mean diameter of 232.3 nm) were resulted. Besides the morphological changes, the size of processed nanoformulations was increased with an increment of the solution concentrations. X-ray diffraction results as well as DSC thermograms clearly indicated that the drug crystallinity decreased in the electrosprayed samples. Furthermore, in vitro dissolution test showed that the electrosprayed samples had relatively slower release patterns toward the pure drug and physical mixtures, where the samples with the drug:polymer ratio of 1:10 indicated a faster release rate toward 1:5 ratio; nevertheless, the concentration of the injected formulations did not remarkably impressed the release behaviours. The current study established the suitability of electrospraying method in the fabrication of the water-soluble drugs nanobeads/nanofibres; however, in vivo effectiveness of the prepared nanoformulations should be meticulously considered.

Methylprednisolone acetate-loaded hydroxyapatite nanoparticles as a potential drug delivery system for treatment of rheumatoid arthritis: In vitro and in vivo evaluations.

The objective of this study was to improve the therapeutic efficacy of methylprednisolone acetate (MPA) in the treatment of rheumatoid arthritis (RA) by incorporating the drug into the hydroxyapatite (HAp) nanoparticles. The nanoparticles were synthesized using a chemical precipitation technique and their size and morphology were evaluated by dynamic light scattering and scanning electron microscopy (SEM). The solid-state behavior of the nanoparticles was also characterized by operating X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The Brunauer-Emmett-Teller and Barrett-Joyner-Halenda N2 adsorption/desorption analyses were also performed to determine the surface area, Vm (the volume of the N2 adsorbed on the one gram of the HAp when the monolayer is complete) and the pore size of the samples. Furthermore, the therapeutic efficacy of the prepared nanoformulation on the adjuvant induced arthritic rats was assessed. HAp mesoporous nanoparticles with a particle size of 70.45nm, pore size of 2.71nm and drug loading of 44.53% were obtained. The specific surface area of HAp as well as the Vm values were decreased after the drug loading process. The nanoformulation revealed the slower drug release profile compared to the pure drug. The MTT assay indicated that the MPA-loaded nanoparticles had a lower cytotoxic effect on NIH-3T3 and CAOV-4 cell lines compared to the pure drug. Interestingly, the in vivo study confirmed that the drug-loaded nanoparticles could considerably decrease the paw volume and normalize the hematological abnormalities in the arthritic rats.

Physicochemical characterization and in vivo evaluation of triamcinolone acetonide-loaded hydroxyapatite nanocomposites for treatment of rheumatoid arthritis.

The current study was aimed to investigate the anti-inflammatory effect of triamcinolone acetonide-loaded hydroxyapatite (TA-loaded HAp) nanocomposites in the arthritic rat model. The HAp nanocomposites were synthesized through a chemical precipitation method and the drug was subsequently incorporated into the nanocomposites using an impregnation method. The physicochemical properties as well as cytotoxicity of the prepared nanoformulation were examined as well. To evaluate the therapeutic efficacy of the prepared nanoformulation, the various parameters such as paw volume, haematological parameters and histological studies were assessed in the arthritic rats. The nanocomposites with the particle size of 70.45 nm, pore size of 2.71 nm and drug loading of 41.94% were obtained in this study. The specific surface area (aBET) as well as the volume of nitrogen adsorbed on one gram of HAp to complete the monolayer adsorption (Vm) were decreased after the drug loading process. The prepared nanoformulation revealed the slower drug release profile compared to the pure drug. Furthermore, the obtained data from MTT assay showed that the TA-loaded nanocomposites had a lower cytotoxic effect on NIH-3T3 and CAOV-4 cell lines as compared to the pure drug. Furthermore, TA-loaded HAp nanocomposites demonstrated favorable effects on the paw volume as well as the haematological and histopathological abnormalities in the adjuvant-induced arthritic rats. Therefore, TA-loaded HAp nanocomposites are potentially suggested for treatment of rheumatoid arthritis after further required evaluations.

Preparation and evaluation of novel metronidazole sustained release and floating matrix tablets.

In the present study, metronidazole was used for preparing floating dosage forms that are designed to retain in the stomach for a long time and have developed as a drug delivery system for better eradication of Helicobacter Pylori in peptic ulcer diseases. For this means, various formulations were designed using multi-factorial design. HPMC, psyllium and carbopol in different concentrations were used as floating agents, and sodium bicarbonate was added as a gas-forming agent. Hardness, friability, drug loading, floating ability and release profiles as well as kinetics of release were assessed. Formulations containing HPMC as filler showed prolonged lag times for buoyancy. Adding psyllium to these formulations had reduced relative lag times. Overall, selected formulations were able to float immediately and showed buoyancy for at least 8?h. Meanwhile, sustained profiles of drug release were also obtained. Kinetically, among the 10 assessed models, the release pattern of metronidazole from the tablets fitted best to Power law, Weibull and Higuchi models in respect overall to mean percentage error values of 3.8, 4.73 and 5.77, respectively, for calcium carbonate-based tablets and, 2.95, 6.39 and 3.9, respectively, for calcium silicate-based tablets. In general, these systems can float in the gastric condition and control the drug release from the tablets.

Reciprocal powered time model for release kinetic analysis of ibuprofen solid dispersions in oleaster powder, microcrystalline cellulose and crospovidone.

PURPOSE: A physically sound derivation for reciprocal power time (RPT) model for kinetic of drug release is given. In order to enhance ibuprofen dissolution, its solid dispersions (SDs) prepared by cogrinding technique using crospovidone (CP), microcrystalline cellulose (MC) and oleaster powder (OP) as a novel carrier and the model applied to the drug release data. METHODS: The drug cogrounds with the carriers were prepared and subjected to the dissolution studies. For elucidation of observed in vitro differences, FT-IR spectroscopy, X-ray diffraction patterns, DSC thermograms and laser particle size measurement were conducted. RESULTS: All drug release data fitted very well to newly derived RPT model. The efficiency of the carriers for dissolution enhancement was in the order of: CP>OP>MC. The corresponding release kinetic parameter derived from the model, t50% (time required for 50% dissolution) for the carrier to drug ratio 2:1 were 2.7, 10.2 and 12.6 min, respectively. The efficiency of novel carrier, OP, was between CP and MC. FT-IR showed no interaction between the carriers and drug. The DSC thermograms and X-ray diffraction patterns revealed a slight reduced crystallinty in the SDs. Also grinding reduced mean particle size of drug from 150.7 to 44.4 microm. CONCLUSIONS: An improved derivation for RPT model was provided which the parameter of the model, t50%, unlike to previous derivations was related to the most important property of the drug i.e. its solubility. The model described very well drug release kinetics from the solid dispersions. Cogrinding was an effective technique in enhancing dissolution rate of ibuprofen. Elaeagnus angostifolia fruit powder was suggested as a novel potential hydrophilic carrier in preparing solid dispersion of ibuprofen.

Propranolol hydrochloride osmotic capsule with controlled onset of release.

Hard gelatin capsule was coated by a cellulose acetate as a semipermeable membrane with or without castor oil and filled with propranolol hydrochloride and sorbitol as an osmotic agent. After sealing the capsule with white bees wax plug, the onset of release and dissolution rate of the drug were studied. Water penetration into the capsule from the dissolution medium increases simultaneously the osmotic and hydrostatic pressures of its content. When the hydrostatic pressure is high enough to overweigh the gravity and frictional forces of the plug, the expulsion of the plug occurs and drug release starts. The effects of thicknesses of the membrane and plug as well as the concentrations of cellulose acetate and castor oil on the onset of drug release were presented by a polynomial model. We found that the effect of plug thickness on the onset of release is more important when the membrane is thicker. The results showed that the presence of caster oil in coating formulation (cellulose acetate 10% or 15%) increased the onset of release (t(o) values). The onset of release varied from 0.6 to 10.5 hr among which the onset times of 4.2, 4.8, 5.9, 5.5, 7.5, 5.0, 7.8 and 10.5 hr could be of use for either chronotherapeutic purposes in protection of patients against heart attacks and strokes during early morning hours or reducing daily frequency of dosage.

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.