فهرست مطالب morteza rafiee-tehrani

Metoprolol has been widely used for controlling high blood pressure, preventing myocardial reinfarction, setting rate changes, setting heart rhythm, treatment of chronic angina and preventing excessive bleeding during surgery. The purpose of this research is formulation and manufacture of extended release tablets of metoprolol succinate that conform to all the in vitro physicochemical US Pharmacopoeia national formulary (USP32). For preparing the tablets, the hydrophilic HPMC(K100M) polymer was used in direct compression method. Release of metoprolol in phosphate buffer having pH=6.8 (USP32) was measured by HPLC. Also, using experimental correlation of diffusivity in buffer medium and Gurney-Lurie charts during tablet enlargement with time, diffusion coefficients of drug and partition coefficients were obtained at different time steps. The rate of drug release depends on the type, viscosity and polymer concentration. Drug release results over 20 hours for polymers of HPMC(K100M), HPMC(K4M), HPMC(K15M), polyethylene oxide, ethyl cellulose, Eudragit (RL100) were investigated and compared. The results demonstrated that HPMC(K100M) met the standards of USP32 very well and was superior over the other polymers tested.

Nutritional supplements have long been one of the most important health products in the world. The therapeutic approach of traditional medicine in Iran is restoring balance in the body based on nutrition. In modern medicine, nutritional supplements maintain and promote health. Nutritional supplements in modern medicine supplement the substances that humans need to obtain from sources other than food to compensate for the lack of these substances. Today, various needs such as reduced mobility due to mechanization of activities, changes in diet and use of prepared foods, non-organic food, environmental pollution, food diversity reduction, renders nutritional supplements more important. The market is expanding rapidly..Nomenclature of these products, their legal requirements, claims, applications and related requirements vary from country to country.

This study examines the regulation of nutritional supplements in Iran compared with some other countries. This study done via a mixed method, included reviewing the regulation of nutritional supplements in Iran and the world, interviewing experts, and use of a questionnaire based survey.

According to the results of this study, the Iranian regulatory situation is well regulated and the nutritional products in Iran have good quality, safety, efficiency and pharmaceutical quality.

Although the regulations in Iran properly granted safety, efficacy, and quality of nutritional supplements, in terms of access (accessibility, availability, and affordability), there are still problems that need to be addressed by policymakers in the health system.

In diabetic patients, insulin secretion from the pancreas is altered which leads to daily insulin injection. Insulin injection causes infection, pain, and stress in the long term. Oral insulin delivery can be an appropriate alternative for injection. However, in oral delivery, due to enzymatic degradation in the gastrointestinal tract, low stability in gastric pH, and physical barriers of intestinal epithelium layer, insulin bioavailability is low. Thus, the synthesis of effective carriers such as nanoparticles can be a suitable solution for protecting sensitive drugs such as insulin. This study aims to develop a Nano-sized system of alginate/ trimethyl chitosan (TMC)/ polyethylene glycol (PEG) system in order to control the insulin release and increase the residence time of the nanoparticles in the gastrointestinal tract. At first, the size of the nanoparticles and Entrapment Efficiency (EE) of insulin were optimized and the optimal conditions for alginate/ insulin, alginate/ TMC ratios, and stirring rate were 1, 4.5, and 500 rpm, respectively. Then, at optimal conditions, insulin loaded alginate nanoparticles were prepared, followed by coating with TMC and finally, the nanoparticles were PEGylated with methoxy polyethylene glycol (mPEG). After optimization, the sizeof the nanoparticles and EE obtained as 195 nm and 92.39%, respectively, and Loading Efficiency (LE) of insulin was calculated as 21.75%. Interaction between the different layers also, was verified using FT-IR analysis andin vitro, insulin release investigation was carried out in Simulated Gastric Fluid (SGF) and Simulated Intestinal Fluid (SIF). These studies showed that the highest insulin release takes place within the initial 6 h, and then the release trend will be constant. Also, insulin release significantly was increased by nanoparticle pegylation.

Cancer is a fatal disease and relatively widespread in the world; Breast cancer is the most prevalent cancer among women. Hydroxyurea (HU) is a chemotherapy drug for the cure of cancer different types in patients, for example breast cancer, but has several defects, for to remove these problems in this study a nanoliposome (NL) suspension for Hydroxyurea (HU) delivery in breast cancer cell therapy was developed.HU was encapsulated into NLs. Size was measured by nanosizer. The release of the liposomal formulation was assessed during 36 h. FTIR analysis for liposomal Hydroxyurea and free Hydroxyurea was carried out. The uptake capacity of the formulation was determined by transfection of nanoliposomal hydroxyurea (NL-HU) in MDA-MB231 cells via flow cytometer and fluorescence microscopy studies, the cytotoxicity of NL-HU and free HU was evaluated in cells. Size of NL-HU was 174nm, HU encapsulation efficiencies in NLs was 81%. FTIR analysis showed the stability of HU in the liposome and no improper interaction between liposome and HU, release after 36h depicted sustained release behavior.NL-HU had suitable uptake in MDA-MB231 cells. Cytotoxicity of NL-HU on cells was considerable. We confirmed these nanoliposomes are potentially useful for delivery of Hydroxyurea in breast cancer cells treatment.

Hydroxyurea (HU) is a well-known chemotherapy drug with several side effects which limit its clinical application. This study was conducted to improve its therapeutic efficiency against breast cancer using liposomes as FDA-approved drug carriers.

PEGylated nanoliposomes-containing HU (NL-HU) were made via a thin-film hydration method, and assessed in terms of zeta potential, size, morphology, release, stability, cellular uptake, and cytotoxicity. The particle size and zeta potential of NL-HU were specified by zeta-sizer. The drug release from liposomes was assessed by dialysis diffusion method. Cellular uptake was evaluated by flow cytometry. The cytotoxicity was designated by methyl thiazolyl diphenyl-tetrazolium bromide (MTT) test.

The size and zeta value of NL-HU were gotten as 85 nm and -27 mV, respectively. NL-HU were spherical.NL-HU vesicles were detected to be stable for two months. The slow drug release and Weibull kinetic model were obtained. Liposomes considerably enhanced the uptake of HU into BT-474 human breast cancer cells. The cytotoxicity of NL-HU on BT-474 cells was found to be significantly more than that of free HU.

The results confirmed these PEGylated nanoliposomes containing drug are potentially suitable against in vitro model of breast cancer.

Insulin therapy has been the best choice for the clinical management of diabetes mellitus. The current insulin therapy is via subcutaneous injection, which often fails to mimic the glucose homeostasis that occurs in normal individuals. Oral delivery is the most convenient administration route. However, insulin cannot be well absorbed orally because of its rapid enzymatic degradation in the gastrointestinal tract. Therefore, nanoparticulate carriers such as polymeric nanoparticles are employed for the oral delivery of insulin. This study aims at the statistical optimization by Box-Behnken statistical design, fabrication by ionic gelation technique and in vitro characterization of insulin nanoparticles containing thiolated N- dimethyl ethyl chitosan (DMEC-Cys) conjugate. Independent variables such as the concentrations of polymer, TPP and insulin were optimized using a 3-factor, 3-level Box–Behnken statistical design. The selected dependent variables were size, zeta potential, PdI and associated efficiency of nanoparticles. The optimized nanoparticles were shown to have mean particle size diameter of 148 nm, zeta potential of 15.5 mV, PdI of 0.26 and AE of 97.56%. In vitro release study, FTIR, FE-SEM and cytotoxicity also indicated that nanoparticles made of this thiolated polymer are good candidate for oral insulin delivery.

In this study, N,N-Dimethyl-N-Octyl chitosan was synthesized. Nanoparticles containing insulin were prepared using PEC method and were statistically optimized using the Box-Behnken response surface methodology. The independent factors were considered to be the insulin concentration, concentration and pH of the polymer solution, while the dependent factors were characterized as the size, zeta potential, PdI and entrapment efficiency. The optimized nanoparticles were morphologically studied using SEM. The cytotoxicity of the nanoparticles on the Caco-2 cell culture was studied using the MTT cytotoxicity assay method, while the permeation of the insulin nanoparticles across the Caco-2 cell monolayer was also determined. The optimized nanoparticles posed appropriate physicochemical properties. The SEM morphological studies showed spherical to sub-spherical nanoparticles with no sign of aggregation. The in-vitro release study showed that 95.5 ± 1.40% of the loaded insulin was released in 400 min. The permeability studies revealed significant enhancement in the insulin permeability using nanoparticles prepared from octyl chitosan at 240 min (11.3 ± 0.78%). The obtained data revealed that insulin nanoparticles prepared from N,N-Dimethyl-N-Octyl chitosan can be considered as the good candidate for oral delivery of insulin compared to nanoparticles prepared from N,N,N-trimethyl chitosan.

The purpose of this study is about the preparation and evaluation of nanoparticles composed of thiolated methylated pyridinyl chitosan (TMPC) which are made P.E.C method, for bucal drug delivery of insulin.
First of all have to synthesize methylated pyridinyl chitosan and then for (TMPC) L-cysteine should be attached to methylated pyridinyl chitosan by the formation amid bounds. After of synthesis the (TMPC) nanoparticles were made and insulin loaded on them. The percentage of entrapment efficiency which was calculated for a nanoparticle which loaded by insulin is about to 91.6%.
The release of insulin from nanoparticles was studied in vitro in Phosphate buffer solution (PBS) pH 6.8. After 240 minutes 71.3% of insulin released from (TMPC) and after 360 minutes 72.9% of insulin was released. By considering the specifications of nanoparticles which leads us to this result that the Zeta potential is 28.3 mv, poly dispersity index (pdi) is 0.33 and the size of the particles is about to 268 nm.
this study suggests that thiolated methylated pyridinyl chitosan can act as a potential enhancer for bucal delivery of insulin.

The treatment of posterior eye diseases is always challenging mainly due to inaccessibility of the region. Many drugs are currently delivered by repeated intraocular injections..

The purpose of this study was to investigate the potential applications of natural triglycerides as alternative carriers to synthetic polymers in terms of drug release profile and also biocompatibility for intraocular use..

In vitro/in vivo evaluations of intravitreal implants fabricated from the physiological lipid, glyceride tripalmitate containing clindamycin phosphate as a model drug was performed. The micro-implants with average diameter of 0.4 mm were fabricated via a hot melt extrusion method. The extrudates were analyzed using scanning electron microscopy, differential scanning calorimetry, and in vitro drug dissolution studies. For biocompatibility, the implants were implanted into rabbit eyes. Clinical investigations including fundus observations, electroretinography as well as histological evaluations were performed..

In vitro tests guaranteed usefulness of the production method for preparing the homogenous mixture of the drug and lipid without affecting thermal and crystalinity characteristics of the components. In vitro releases indicated a bi-phasic pattern for lower lipid ratios, which were completed by the end of day three. With higher lipid ratios, more controlled release profiles were achieved until about ten days for a lipid ratio of 95%. Clinical observations did not show any abnormalities up to two months after implantation into the rabbit eye..

These results suggest that although the implant could not adequately retard release of the present drug model yet, due to good physical characteristics and in vivo biocompatibility, it can represent a suitable device for loading wide ranges of therapeutics in treatment of many kinds of retinochoroidal disorders..

All contemporary methods of insulin administration are non-physiological. The euglycemia that is achieved in at the expense of the adverse effects of systemic hyper-insulinemia, emphasize the importance of devising methods to deliver insulin physiologically and directly into the portal circulation. The aim of the present study was to evaluate the oral absorption of insulin from gastrointestinal tract, using novel oral drug delivery system delivery based on superporouse hydrogel (SPH) and SPH composite (SPHC) in combination with insulin. This study has been done based on interventional clinical trial in healthy volunteers. Capsules containing insulin and SPH &SPHC in various combination were administered orally, to 15 non-diabetics subjects in order to assess this biological effects and safety. Serum glucose, insulin and C - peptide levels were determined, at predetermined timed intervals up to 4 h. An increase in serum insulin level was demonstrated in all subjects that used polymer plus insulin. The nadir of serum glucose level appeared after 60 - 120 min following the ingestion of polymer plus insulin. Serum C - peptide levels were suppressed while exogenous insulin was absorbed at the same time. No adverse effects were detected during the trial and several weeks following the trial using SPH based drug delivery system. Insulin in combination with novel delivery agents, SPH & SPHC, given orally was partially absorbed through the GI tract in a biologically active form. This was demonstrated by serum glucose lowering effect of the delivery system as well as a suppression of plasma C-peptide which also represented a decrease in endogenous insulin secretion.

All contemporary methods of insulin administration are non-physiological. The euglycemia that is achieved in at the expense of the adverse effects of systemic hyper-insulinemia, emphasize the importance of devising methods to deliver insulin physiologically and directly into the portal circulation. The aim of the present study was to evaluate the oral absorption of insulin from gastrointestinal tract, using novel oral drug delivery system delivery based on superporouse hydrogel (SPH) and SPH composite (SPHC) in combination with insulin.
This study has been done based on interventional clinical trial in healthy volunteers. Capsules containing insulin and SPH &SPHC in various combination were administered orally, to 15 non-diabetics subjects in order to assess this biological effects and safety. Serum glucose, insulin and C - peptide levels were determined, at predetermined timed intervals up to 4 h.
An increase in serum insulin level was demonstrated in all subjects that used polymer plus insulin. The nadir of serum glucose level appeared after 60 - 120 min following the ingestion of polymer plus insulin. Serum C - peptide levels were suppressed while exogenous insulin was absorbed at the same time. No adverse effects were detected during the trial and several weeks following the trial using SPH based drug delivery system.
Insulin in combination with novel delivery agents, SPH & SPHC, given orally was partially absorbed through the GI tract in a biologically active form. This was demonstrated by serum glucose lowering effect of the delivery system as well as a suppression of plasma C-peptide which also represented a decrease in endogenous insulin secretion.

All contemporary methods of insulin administration are non-physiological. Insulin is not absorbed from the gastrointestinal tract because of its peptide nature. The aim of the present study was to examine the absorption of oral insulin from gastrointestinal tract, using novel oral formulation- adding a delivery agent superporouse hydrogel (SPH) and SPH composite (SPHC) in combination with insulin. Capsules containing insulin and SPH &SPHC were administered orally, to 15 non-diabetic subjects in order to assess its biological effects and safety. Plasma glucose, insulin and c – peptide serum levels were determined, at timed intervals up to 4 h. In the present study, we showed that AUC of exogenous insulin in polymer -insulin group was higher than sub-cutaneous regular insulin group. It means that addition of SPHC polymer caused increase in insulin absorbtion.In addition, Insulin Tmax in polymer group was longer than sub-cotaneaus insulin group. Blood glucose AUC in sub-cotaneaus group was higher than polymer group.AUC C-peptide serum level in polymer group was higher than sub-cutaneous group. Insulin in combination with a novel delivery agent, SPH and SPHC, given orally is absorbed through the GI tract in a biologically active form. This was demonstrated by suppression of endogenous insulin secretion.

All contemporary methods of insulin administration are non-physiological. Insulin is not absorbed from the gastrointestinal tract because of its peptide nature.
The aim of the present study was to examine the absorption of oral insulin from gastrointestinal tract, using novel oral formulation- adding a delivery agent superporouse hydrogel (SPH) and SPH composite (SPHC) in combination with insulin.
Capsules containing insulin and SPH &SPHC were administered orally, to 15 non-diabetic subjects in order to assess its biological effects and safety. Plasma glucose, insulin and c - peptide serum levels were determined, at timed intervals up to 4 h.
In the present study, we showed that AUC of exogenous insulin in polymer -insulin group was higher than sub-cutaneous regular insulin group. It means that addition of SPHC polymer caused increase in insulin absorbtion.In addition, Insulin Tmax in polymer group was longer than sub-cotaneaus insulin group.
Blood glucose AUC in sub-cotaneaus group was higher than polymer group.AUC C-peptide serum level in polymer group was higher than sub-cutaneous group.
Insulin in combination with a novel delivery agent, SPH and SPHC, given orally is absorbed through the GI tract in a biologically active form. This was demonstrated by suppression of endogenous insulin secretion.

Biodegradable polymers such as chitosan have been used extensively in biomedical fields in the form of sutures; wound dressing and as artificial skin. Colonic drug delivery for either local or systemic effects has been the subject of much research over the last decade. Chitosan exhibits poor solubility at pH values above 6 that prevent enhancing effects at sites of absorption of drugs. In the present work, N-diethyl methyl chitosan (DEMC) was prepared based on a modified two-step process via a 22 factorial design to optimize the preparative conditions. DEMC Polymer with different degrees of quaternization for pharmacological and pharmaceutical experiments was achieved. The reaction was optimized using different amounts of reactants. pH-metric titration and infrared methods predetermined the degree of deacetylation of the starting chitosan. DEMC Chloride was characterized using FTIR and 1H NMR spectroscopies. Based on NMR calculation, high degree of quaternization was achieved through the optimized twostep process. Under our optimized conditions, (i.e. the second step, chitosan 1.5%, ethyl iodide 30%, NaOH 3.1%, 60°C, 6h), the prepared DEMC comprised a degree of quaternization of 79%. The prepared N-diethyl methyl chitosan chlorides were rapidly and completely dissolved in water at room temperature.

Abstract: Salbutamol sulphate (SS) was precipitated by supercritical carbon dioxide (SC-CO2) using a homemade system at two different pressures. This process is characterized by spraying a methanolic solution of the drug into the supercritical fluid (SCF), extraction of the solvent by SC-CO2 and formation of drug particles. The morphology and size distribution of precipitated SS particles were characterized using scanning electron microscope and laser diffraction particle size analyzer respectively. FTIR spectra were used before and after processing to asses crystal modifications. Depending on the processing conditions, needle-like and flake-like particles with different size distributions were observed. The average size of the flake like particles was less than needle-like particles and the span parameter showed a narrower size distribution of the processed in comparison with the unprocessed materials. Analysis by FTIR showed that there was no significant effect on the structure of the drug under these processing conditions.