فهرست مطالب hadi valizadeh

Lipid-based drug delivery systems (DDS) can improve the pharmacokinetic (PK) parameters of some drugs. Especially those with a high volume of distribution (Vd) leading to off-target accumulation and toxicity. Amiodarone as an anti-arrhythmic agent induces hypothyroidism and liver disorders limiting its clinical indication.

In the present study, amiodarone PK parameters and biodistribution after IV administration of four nano-formulations to rats were compared. The formulations were liposomes, solid lipid nanoparticles (SLN), PEGylated SLN (PEG-SLN), and nanoemulsions (NE). All formulations were optimized.

The nanoparticles were spherical with a diameter of 100-200 nm and sustained in vitro drug release in buffer pH 7.4. The best-fitted model for the plasma concentration-time profile was two-compartmental. In vivo studies indicated the most changes in PKs induced after liposome, SLN, and NE administration, respectively. The area under the curve (AUC) and maximum plasma concentration (Cmax) of liposomes, SLN, and NE were 22.5, 2.6, 2.46 times, and 916, 58, and 26 times higher than that of amiodarone solution, respectively (P-value<0.05). The heart-to-liver ratio of amiodarone was higher for nano-formulations compared to drug solution except for liposomes.

Lipid-based particles can improve the PK parameters of amiodarone and its distribution in different tissues.

 Pressure lesions are chronic wounds causing the development of infection and inflammation into deeper structures and finally necrosis. In Persian medicine, Alkanna orientalis (Boraginaceae) has been used for centuries as a naturally derived remedy for managing lesions. A cross-sectional pilot clinical trial was conducted to assess the wound healing effect of an ointment made of chloroform extract of roots of A. orientalis (CERAO).

 Sixty patients (36 men and 24 women) diagnosed with bedsore staging 1-2 entered the study for one year. They were divided into two groups of control and treatment with equal proportions. The control group received conventional treatment from the hospital, including irrigation serum, mupirocin, phenytoin ointments, and gauze dressing. After rinsing and cleansing with normal saline, in the intervention group, patients received a thin layer of CERAO once daily for four weeks. Clinical outcomes were measured at weeks 2 and 4.

 Recovery assessment was carried out by measuring wound area, days of epithelia formation, and complete wound closure. The difference between the two groups was statistically significant (P-value <0.05) in terms of the mentioned criteria. The recovery percentage was 26.7% and 60% for the control and treatment groups, respectively. In the control group, 16.7% of the study population experienced the development of wounds, while in the intervention group, wound progression was not observed.

 The results of this pilot study indicated that the clinical efficacy of CERAO could be promising and a replacement for conventional treatment of pressure ulcers.

Poor aqueous solubility hampers the development of several compounds as pharmacological agents. Hence, preparing novel formulations with augmented absorption is a challenge in pharmaceutical industries. In this paper, we have examined the effect of basic amino acids including arginine (ARG), lysine (LYS), and glucosamine (GlucN) on the solubility of ibuprofen (IBU) and piroxicam (PXM) as drugs with limited solubility. We have also studied the effect of the dissolution media with the pH values 1.2 to 7.4.

The saturation shake-flask method was used for solubility studies in the presence of amino acids. Briefly, buffer solutions containing different concentrations of amino acids were prepared. Then, an excess amount of each drug with these buffers was shaken to reach equilibrium. After 48 hours, the upper phase was separated, and solubility was calculated by reading their UV-Vis absorbance.

The results illustrated that amino acids increased solubility of both drugs with different ratios, which were pH and concentration-dependent. Solubility improved as the amount of amino acids went up, and this upward pattern was more robust with ARG than LYS. The presence of GlucN in citrate buffer significantly enhanced IBU solubility. The solubility of PXM in accompany of GlucN in water did not change significantly while in citrate buffer solubility enhanced specially at pH 6.

Overall, GlucN in citrate buffer and ARG in phosphate buffer could be introduced as the most suitable media for IBU and PXM solubility improvement, respectively.

Solid lipid nanoparticles (SLNs) are colloidal carriers made up of lipids that are stabilized by surfactant molecules. The lipid matrix remains solid at body temperature. A significant challenge in the preparation of SLNs is determining the optimal concentration of surfactants due to their potential toxicity.

During the preparation of SLNs, micelle structures tend to form at high concentrations of surfactants. Since micelles exhibit different properties from SLNs, using the optimum concentration of surfactants leads to the preparation of a consistent formulation of SLNs. This was theoretically predicted in this study and then compared with experimental results.

In this study, amiodarone-loaded SLNs were produced via a hot homogenization process. The design of experiments was utilized to explore effective process parameters, as several factors influence the formulation characteristics. The concentration of surfactants was optimized using a Box-Behnken design. The results were compared with a theoretical equation developed in this study, which estimates the concentration of surfactants needed to cover the surface of the particles. Assessments included particle size and morphology, size distribution, drug loading percentage (DL%), and encapsulation efficiency (%).

The particle size of the optimum formulation was 74 ± 1.5 nm, with DL% and EE% being 14.81 ± 0.8% and 97.58 ± 2.5%, respectively. The formulation contained 2.3% Witepsol, 0.25% glyceryl monostearate (GMS), 0.5% amiodarone (AMI), 0.02% sodium lauryl sulfate (SLS), 0.05% poloxamer, and 0.17% lecithin. The total surface area of the particles was estimated according to the equation 6× (volume of the lipid phase)/ (diameter of particles), which can be applied to determine the concentration of surfactants required for preparing SLNs.

The results indicated that the theoretical equation was suitable for estimating the optimum concentration of surfactant in the aqueous phase to form SLNs and adequately cover the lipid surface. Mathematical estimations were comparable to the experimental results from the Box-Behnken design. Consequently, the formulation consisted of SLNs without any micellar structure, and the applied concentrations of surfactants effectively covered the surface of the particles.

Enoxaparin is low-molecular-weight heparin administered by subcutaneous/intravenous injection. The oral bioavailability of enoxaparin is restricted by its low absorption through the intestine. In this study cell-penetrating peptide-surface functionalized liposomes (CPPs-L) were prepared to improve the intestinal absorption of enoxaparin.

Liposomal formulations were prepared by the ethanol injection method and the intestinal absorption of the formulation was evaluated using the single-pass intestinal perfusion (SPIP) technique in rats. Meanwhile, the human fraction dose absorbed value (Fa (human)) of the formulations was predicted based on the calculated effective intestinal permeability (P effect (rat)) values obtained from the SPIP study.

Liposomal enoxaparin revealed an increased intestinal absorption by ten-time compared with the free drug solution. Meanwhile, CPPs-L formulation revealed an enhanced intestinal absorption compared with the un-modified liposomal formulation. Regarding Fa (human), it is predicted that liposomal formulations could have the potential to improve the fraction dose absorbed of enoxaparin from low to intermediate levels.

Overall, the liposomal formulation can be considered as a mighty drug carrier for the oral delivery of enoxaparin.

Sarcocystis is one of the most typical parasites in domestic animals, affecting cattle, sheep, and goats. The meat business loses millions of dollars each year due to the eradication of Sarcocystis-infected carcasses. In humans, some Sarcocystis species induce digestive problems such as nausea, vomiting, and diarrhea. Because this parasite is usually found in skeletal and cardiac muscles, it is crucial and required to provide preventative and control strategies such as inactivating or eradicating the bradyzoites in contaminated meat. The employment of freezing and heating temperatures is one of these methods. The main objective of this study was to investigate the effects of freezing and heating temperatures on the survival rate of Sarcocystis bradyzoites in infected mutton. To verify the presence of contamination in meat, two methods of Dob smear and digestion were applied. The samples were then exposed to heat and cold, and the mortality rate was determined using a digestion method. ANOVA and LSD post hoc tests were employed to assess the association between the variables (P ˂ 0.05). The results showed that temperature of 100 ºC for 10 minutes and temperature of 80 ºC and for above 20 minutes were effective in killing the parasites. Also, the parasites were completely disappeared after 24 hours at -20 ºC. The findings revealed that the bradyzoites did not have a substantial mortality rate at 4 ºC for up to six days. As a result, this parasite can be killed by heating or freezing.

Sarcocystis is a mandatory intracellular parasite that is common between humans and animals, which causes huge losses in the livestock and meat industries. This study aimed to determine the prevalence of Sarcocystis infection in goats slaughtered in Tabriz slaughterhouse. For this purpose, the carcasses of 240 slaughtered goats were examined for the presence of macrocysts by eye observation and then by microscopic by dob-smear and digestive methods. Based on the results, 2.5% of the studied carcasses were diagnosed with macrocytic observation. In the microscopic examination by dob-smear and digestion methods, 35.83% and 100% respectively of the cases were positively diagnosed. There is a significant relationship between contamination and the studied method (p<0.05), which has higher validity digestion than the dob-smear and macroscopic method. There was also a statistically significant difference between the contamination rate among different muscles (p<0.05). As well, the highest microcyst contamination was observed in diaphragm muscles and the lowest microcyst contamination was observed in the heart muscle. This study showed the necessity of microscopic observation of the Sarcocystis contamination in the goat carcasses.

The current study’s objectives were to obtain different extracts and essential oils of Symphytum kurdicum and Symphytum asperrimum and to determine the chemical composition, as well as to evaluate free radical scavenging activity (IC50) and minimum bactericidal concentration (MBC), and the effect of liposomal formulation on antimicrobial properties.

Air-dried powdered aerial parts of S. kurdicum and S. asperrimum were used. The antioxidant and antibacterial properties, essential oil compositions, total phenol, and flavonoid contents of different fractions were determined by DPPH test, disk diffusion assay, gas chromatography-mass spectrometry, Folin-ciocalteu reagent, and colorimetric assay method, respectively. The film hydration method was used to fabricate nanoparticles.

GC-MS analysis indicated that hexafarnesyl acetone was a major essential oil component. n-butanol and ethyl acetate extracts of S. kurdicum had the highest anti-oxidant activity. Extracts of both plants showed antimicrobial activity. The extracts’ maximum inhibition zones against Staphylococcus epidermidis were established. A particle size analyzer detected the formulation size of 140 nm. The optimum formulation of liposomes contains the ratio of 75 mg lecithin, 25 mg cholesterol, and 50 mg herbal extract. Despite the nanoparticles’ appropriate particle size, the liposomal extract’s antimicrobial effect was lower than that of the free form.

Our findings demonstrated that extracts have significant antibacterial and anti-oxidant activities, attributed to their bioactive constituents.

The eradication of Sarcocystis-infected corpses costs the meat industry millions of dollars each year. Because this parasite is most commonly found in skeletal and cardiac muscles, preventative and control techniques such as inactivating or destroying the bradyzoites in infected meat are critical. The goal of this research was to look at the various methods for inactivating this parasite and to compare the results of these methods. Using internet databases from many fields and around the world, a systematic review of the literature was conducted. Heating, freezing, irradiation, and marination were all utilized to inactivate this parasite, and each had a distinct effect, according to the studies. Inactivation can be achieved by heating at 60°C for 20 min or freezing at -4ºC for 2 days. Also, 2 kGy of gamma rays and marination in 6% NaCl and 3% acetic acid for 48 h are enough.

Liver trematodes, including Fasciola and Dicrocoelium species, are zoonotic parasites that cause high mortality and economic losses in ruminants. This study aimed to investigate the effect of age, sex, and season on the prevalence of fasciolosis and dicrosliosis in slaughtered animals in the Tabriz slaughterhouse. During two years, livers of 4150 cows, 500 buffaloes, 2000 goats, and 5000 sheep were examined for the presence of Fasciola hepatica, Fasciola gigantica, and Dicrocoelium dendriticum by incisions on the liver and ocular observation. The results showed that 5.4%, 16%, and 6% of slaughtered cows, sheep, and goats were infected with liver trematodes (P<0.05), respectively. Of the 500 buffaloes studied, no liver trematode was isolated. The prevalence of parasitic infection in all three animals increased significantly with the age (P<0.05). In female cows and sheep, the rate of liver trematode infection was significantly higher than in males (P<0.05). The highest and lowest prevalence was observed in summer in spring, respectively. The highest frequency of parasites and severity of infection in all studied animals was related to Dicrocoelium dendriticum and the lowest was related to Fasciola gigantica (P<0.05). Based on the market day price, the number of economic losses due to the condemnation of liver of cows, sheep, and goats due to trematode infections were estimated at 402,240,000 (3656.72 USD), 576,576,000 (5241.6 USD), and 28,545,000 (259.5 USD) RIAL, respectively. Due to the history of the human fascioliasis epidemic and economic damage caused by liver condemnation in this area, effective control methods are suggested.

Methotrexate (MTX) is one of the most effective therapeutics to treat different types of solid tumors; however, it suffers low permeability limiting its bioavailability and cellular uptake. To tackle this, we aim to design and fabricate different types of cell-penetrating peptides (CPPs) to improve the intracellular uptake of MTX without causing any immunogenic response. CPPs were synthesized by the solid-phase peptide synthesis method. Peptide-MTX conjugates were prepared via covalent binding of peptide and drug molecule. CPPs and peptide-E8 nanoparticles were characterized using zeta-sizer and scanning electron microscopy. Cytotoxicity of CPPs and peptide-MTX conjugates was evaluated by MTT assay. An enzyme-linked immunosorbent assay was employed to assess the IL-6 and TNF-α cytokine release profile. Amongst all sequences, W4R4-MTX possessed the highest loading efficiency (97%) and drug to peptide percentage (24.02%). The lowest loading efficiency (36%) and drug to peptide percentage (8.76%) were seen for NGRWK-MTX conjugates. The NGRWR peptide and NGRWR-E8 nanoparticles had acceptable size (~100 nm) with spherical and rod-like structures, respectively. The selected CPPs and peptide-MTX conjugates did not show any cytotoxicity or immunogenicity. The fabricated peptides are represented as promising carriers to improve the intracellular delivery of MTX to cancer cells with low immunogenic and cytotoxic effects on normal cells.

Enoxaparin has been widely used as a choice drug for treatment and prevention of different coagulation disorders. Orally administered enoxaparin encounters with gastrointestinal barrier because of its high water solubility, high molecular weight and significant negative charge. Since, the nano-liposomes has gained great interest for oral drug delivery, we decided to introduce the best protocol for preparing enoxaparin nano-liposomes through in-vitro characterization.

Nano-liposomes were prepared by ethanol injection, thin film hydration, and double emulsion/solvent evaporation methods. Size distribution, zeta potential, loading efficiencies, and in-vitro drug release of nano-liposomes were also studied.

The mean vesicle size was obtained under 100 nm, and the zeta potential was highly negative through all preparation methods. Nano-liposomes prepared by double emulsion/ solvent evaporation (DE) technique could entrap more of this hydrophilic drug (43 ± 7.1 %), but through thin layer hydration (TL) and ethanol injection (EI) only 28.4± 3.2% and 17.3 ± 2.5% of drug could be loaded into synthesized carriers. Drug release from these carriers was also obtained 42.17±1.72%, 29.43±0.34% and 32.27±0.14%, in 24 hours for EI, TL, and DE methods, respectively.

Here, we can introduce double emulsion/solvent evaporation method as an acceptable method for enoxaparin loading, although some toxicity and in-vivo tests are also necessary to fully understand the potential of this formulation.

Doxorubicin (Dox) is one of the most well-known chemotherapeutics that are commonly applied for a wide range of cancer treatments. However, in most cases, efflux pumps like P-glycoprotein (P-gp), expel the taken drugs out of the cell and decrease the Dox bioavailability. Expression of P-gp is associated with elevated mRNA expression of the ATP-binding cassette B1 (ABCB1) gene.

In the current study, different sequences of cell-penetrating peptides (CPPs) containing tryptophan, lysine, and arginine and their nano-complexes were synthesized and their impact on the expression and activity of the ABCB1 gene was evaluated in the A549 lung carcinoma cell line. Furthermore, the cellular uptake of designed CPPs in the A549 cell line was assessed.

The designed peptides, including [W4K4], [WR]3-QGR, R10, and K10 increased Dox cytotoxicity after 48 hr. Furthermore, arginine-rich peptides showed higher cellular uptake. Rhodamin123 accumulation studies illustrated that all the obtained peptides could successfully inhibit the P-gp pump. The designed peptides inhibited the ABCB1 gene expression, of which, [W4K4] resulted in the lowest expression ratio.

[W4K4], [WR]3-QGR, R10, and K10 could successfully increase the Dox cytotoxicity by decreasing the efflux pump gene expression.

Bortezomib (BTZ) as a specific proteasome inhibitor is used to inhibit proliferation and migration of tumor cell in variety of cancers. Targeted delivery of this drug not only would minimize its unwanted side effects but also might improve its efficacy. This purpose could be gotten through different pathways but using efficient carriers may be the best one without using any additional ingredients/ materials. Some polymer based nanoparticles with specific functional groups have the ability to interact with boronic acid moiety in BTZ. This reaction might play an important role not only in cancer targeting therapy but also in loading and release properties of this drug. Novel modification such as making multifunctional or pH-sensitive nanocarriers, may also improve anticancer effect of BTZ. This review might have remarkable effect on researchers’ consideration about other possible interactions between BTZ and polymeric nanocarriers that might have great effect on its remedy pathway. It has the ability to brought bright ideas to their minds for novel amendments about other drugs and delivery systems.

An innovative type called "butterfly-shaped links steel plate shear wall (BLSPSW)" was proposed as a lateral load resisting system. In this novel system, by creating butterfly-shaped links in the four sides of the web plate, the lateral load resisting mechanism is not the development of a diagonal tension field on the web plate (similar to Conventional SPSWs), but the capacity of the system is determined by the shear strength of the links. Therefore, the geometric parameters of the link as initial design inputs affect predicting and controlling the stiffness and strength of the BLSPSW. Three experimental specimens were loaded to examine the behavior of the proposed system. The first one was the conventional steel plate shear wall (called SPSW-1), and two others prepared of the butterfly-shaped link steel plate shear wall (BLSPSW) with links that have been controlled by shear yield (SPSW-BL 80) and flexural yield (SPSW-BL 130). The experimental results showed that the stiffness and strength of the BLSPSW specimens can be controlled by the link geometry. Also, the BLSPSWs indicated desirable ductility up to 10 percent and high energy dissipation, even in small drifts compared to the SPSW-1. At last, the shear strength formulation of the butterfly fuses was used to determine the shear capacity of the BLSPSWs and compared with the experimental results.

Evaluation of drug-excipients compatibility is an important stage during preformulation studies. In the present research, differential scanning calorimetry (DSC) at different heating rates (2.5, 10, 15°C/min) was applied for the kinetic evaluation of fluvoxamine (FLM), sertraline (SER) and doxepin (DOX) binary mixtures with lactose. Solid state kinetic parameters of the mixtures were calculated using two different thermal methods including ASTM E698 and Starink and the effect of amine type (pKa value) was investigated based on the calculated activation energies. Based on obtained results mean activation energy calculated for FLM, SER and DOX with lactose using ASTM E698 and Starink methods are equal to 335.23, 132.02 and 270.99 kJ/ mol respectively. Results showed that the probability of drug-lactose interaction is higher in the SERlactose mixture in comparison with other two antidepressant drugs which is consistent with their pKa values.

White spot lesion is considered as one of the main problems in the orthodontic treatment. Brackets used in fixed orthodontic treatment create an environment that provides enamel demineralization. The objective of the current study was to perform an in vitro study to compare different applications of fluoride supplements on enamel demineralization adjacent to orthodontic brackets and finally to understand the best supplement to recommend the patients. One hundred and twenty extracted caries-free human premolar teeth were randomly assigned into six groups: group 1: Control group, group 2: Fluoride toothpaste, group 3: Fluoride toothpaste/mouth rinse, group 4: Fluoride toothpaste/vanish, group 5: Fluoride toothpaste/gel and group 6: Fluoride toothpaste/foam. After bonding the brackets to the teeth, the fluoride supplements were applied based on each group above, except the control group. Then all the specimens were cycled for 30 days in demineralization solution for 8 hours a day, rinsed, placed in artificial saliva for 4 hours a day, brushed (except the control group), and put back to artificial saliva for 12 hours. DIAGNOdent laser fluorescence was used to quantify the demineralization changes. Significant differences existed between all fluoride-containing groups and control group. Analyses of the results showed a significant difference between control group and the rest 5 treatment groups (P < 0.001). Other significant differences were between groups 2/5, 3/5, 2/4 and 5/6 (P < 0.05). There was no significant difference among the other groups (P > 0.05). According to the results, all fluoride supplements could be used during orthodontic treatment to decrease the enamel demineralization. It has been illustrated that fluoride-containing toothpaste and mouth rinse is better than no fluoride treatment but is not effective as well as fluoride gel and varnish.

In this study chitosan and gallic acid nanogels is producted and three concentration 0 ¡100 ¡200ppm were added to sunflower oil mayonnaise The prepared samples stored for 60 days. particle size determined. Acidi number¡peroxide valu¡ oven shal ¡measuring carotenoid and Fourier transformation infrared (FTIR) spectrometry analysis was investigate . Acidi number and peroxide valu increased during storage time increase in control sample was more than other samples and in 200 ppm sample was lower than rest. In oven Shal test peroxide valu increase during storage time but the increase in the control sample was more than other . Amount of carotenoids in all samples decreased but in control sample carotenoids decrease was more than other samples. Among tree treatment, the sample containing 200 ppm nanogel and control sample had best and wrost results, respectively. The result showed that chitosan gallic acid nanogel could show good antioxidant properties.

Micelles have been studied as nanoparticulate drug delivery systems for improving the topical ocular delivery of hydrophobic drugs. The objective of this study was to develop and characterize dexamethasone-loaded polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) micelles to improve patient compliance and enhance the ocular bioavailability of poorly water-soluble drugs.
The PCL-PEG-PCL copolymers were synthesized via the ring opening polymerization of ε-caprolactone in the presence of PEG. The resulting purified copolymers were characterized by GPC, NMR, FTIR, XRD and DSC. The critical micelle concentrations (CMCs) of the copolymers mentioned were determined. Dexamethasone was loaded into polymeric micelles by film hydration method, and dexamethasone-loaded micelles were characterized by TEM and DLS. Drug release kinetics and ex vivo corneal permeability were also determined.
The CMC of the synthetized copolymers was approximately 0.03 mg/ml. Aqueous solutions of the resulting copolymers (400 mg/ml) rapidly formed a gel in situ at 34 °C. The TEM results exhibited the successful formation of spherical micelles. The size of the prepared micelles was approximately 40 nm. Formulated micelles sustained the release of the incorporated dexamethasone for 5 days.
Data from ex vivo permeability tests indicated that PCL-PEG-PCL micelles can be suitable candidates for the ocular delivery of dexamethasone and, likely, other hydrophobic drugs.

In the present study the incompatibility of FLM (fluvoxamine) with lactose in solid state mixtures was investigated. The compatibility was evaluated using different physicochemical methods such as differential scanning calorimetry (DSC), Fouriertransform infrared (FTIR) spectroscopy and mass spectrometry.
Non-Isothermally stressed physical mixtures were used to calculate the solid– state kinetic parameters. Different thermal models such as Friedman, Flynn–Wall–Ozawa (FWO) and Kissinger–Akahira–Sunose (KAS) were used for the characterization of the drug-excipient interaction.
Overall, the incompatibility of FLM with lactose as a reducing carbohydrate was successfully evaluated and the activation energy of this interaction was calculated.
In this research the lactose and FLM Maillard interaction was proved using physicochemical techniques including DSC and FTIR. It was shown that DSC- based kinetic analysis provides fast and versatile kinetic comparison of Arrhenius activation energies for different pharmaceutical samples.

Many studies have focused on how drugs are formulated in the sol state at room temperature leading to the formation of in situ gel at eye temperature to provide a controlled drug release. Stimuli-responsive block copolymer hydrogels possess several advantages including uncomplicated drug formulation and ease of application, no organic solvent, protective environment for drugs, site-specificity, prolonged and localized drug delivery, lower systemic toxicity, and capability to deliver both hydrophobic and hydrophilic drugs. Self-assembling block copolymers (such as diblock, triblock, and pentablock copolymers) with large solubility variation between hydrophilic and hydrophobic segments are capable of making temperature-dependent micellar assembles, and with further increase in the temperature, of jellifying due to micellar aggregation. In general, molecular weight, hydrophobicity, and block arrangement have a significant effect on polymer crystallinity, micelle size, and in vitro drug release profile. The limitations of creature triblock copolymers as initial burst release can be largely avoided using micelles made of pentablock copolymers. Moreover, formulations based on pentablock copolymers can sustain drug release for a longer time. The present study aims to provide a concise overview of the initial and recent progresses in the design of hydrogel-based ocular drug delivery systems.

In the present paper the physicochemical incompatibility of sertraline with dextrose was evaluated in oral liquid formulations. Different physicochemical methods such as differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy and mass spectrometry were applied to assess sertraline - dextrose incompatibility. Non-Isothermally stressed physical mixtures were used to study the solid–state kinetic parameters. Different thermal models such as Friedman, Flynn–Wall–Ozawa (FWO) and Kissinger–Akahira–Sunose (KAS) were used to calculate the activation energy of drug-excipient interaction. The aim of this study was to evaluate the kinetic parameters using a fast and sensitive DSC method. Overall, the incompatibility of sertraline as an amine containing drug with dextrose as a reducing carbohydrate was successfully evaluated. DSC based kinetic analysis can provide rapid and easy evaluation of different drug-excipient mixtures incompatibilities. Special considerations should be made regarding the Maillard incompatibility reaction in the formulation design of liquid formulations containing dextrose or natural herbal extracts as sweeteners.

Optimization of filgrastim (G-CSF) (granulocyte colony stimulating factor) liposomes formulation prepared by the method of film hydration was the aim of this research.
To study the independent variables effects in the development of filgrastim (G-CSF) liposomes, method of factorial design was applied. The molar ratio of dipalmitoyl phophatidylcholine (DPPC) per cholesterol (Chol.) and hydration time were chosen as two independent factors. The dependent variables were encapsulation efficiency percent (EE %) and particle size (PS). Ultrafiltration method was applied for separation of un-encapsulated protein. RP-HPLC method was employed for analysis of G-CSF.
Application of response surface methodology (RSM) in formulation of filgrastim liposomes and the obtained results for responses including particle size and EE % showed that the main effective independent variable was DPPC/Chol molar ratio. Different impacts of influencing parameters including interaction and individual effects were checked employing a mathematical method for obtaining desired liposomes. Optimum liposomal formulations were established using this method for enhancing their characteristics. Average percent errors (APEs) were 3.86% and 3.27% for predicting EE % and PS, respectively which reflect high model ability in this regard.
It is concluded that observed and predicted values regarding PS and EE % were consistent and this model is efficient enough in prediction of the mentioned characteristics while preparing filgrastim (G-CSF) liposomes.

P-glycoprotein (P-gp) is a trans-membrane drug efflux pump. Several drugs are P-gp substrates. Some drugs may affect the activity of P-gp by inhibiting its function, resulting in significant drug-drug interactions (DDIs). It is critical to understand which drugs are inhibitors of P-gp so that adverse DDIs can be minimized or avoided. This study investigated the effects of gliclazide, metformin, and pioglitazone on the function and expression of P-gp. Rhodamine 123 (Rh 123) efflux assays in Caco-2 cells and western blot testing were used to study in vitro the effect of the drugs on P-gp function and expression. The in situ rat single-pass intestinal permeability model was developed to study the effect of the drugs on P-gp function. Digoxin and verapamil were used as a known substrate and inhibitor of P-gp, respectively. Digoxin levels in intestinal perfusion samples were analyzed by high-performance liquid chromatography. Intestinal effective permeability (Peff) of digoxin in the presence of 0.1, 10, and 500 μM gliclazide, 100 and 7000 μM metformin, and 50 and 300 μM pioglitazone was significantly increased relative to the digoxin treated cells (P 0.05). It was found that gliclazide, metformin, and pioglitazone inhibited P-gp efflux activity in situ and down-regulated P-gp expression in vitro. Further investigations are necessary to confirm the obtained results and to define the mechanism underlying P-gp inhibition by the drugs.

The aim of the present study was investigating the effects of three antiinflammatory drugs, on Sirolimus protein biding. The binding site of Sirolimus on human serum albumin (HSA) was also determined.
Six different concentrations of Sirolimus were separately exposed to HSA at pH 7.4 and 37°C. Ultrafiltration method was used for separating free drug; then free drug concentrations were measured by HPLC. Finally, Sirolimus protein binding parameters was calculated using Scatchard plots. The same processes were conducted in the presence of NSAIDs at lower concentration of albumin and different pH conditions. To characterize the binding site of Sirolimus on albumin, the free concentration of warfarin sodium and Diazepam, site I and II specific probes, bound to albumin were measured upon the addition of increasing Sirolimus concentrations.
Based on the obtained results presence of Diclofenac, Piroxicam and Naproxen, could significantly decrease the percentage of Sirolimus protein binding. The Binding reduction was the most in the presence of Piroxicam. Sirolimus-NSAIDs interactions were increased in higher pH values and also in lower albumin concentrations. Probe displacement study showed that Sirolimus may mainly bind to site I on albumin molecule.
More considerations in co-administration of NSAIDs and Sirolimus is recommended.