Preparation and Physicochemical Evaluation of Cochleate-based Carriers for Insulin

Introduction: Cochleates are  cylindrical lipid structures that are more stable against oxidation and temperature than liposomes.  Our research is formulation of  cochleates for oral delivery of insulin as a model protein drug. Protein drugs are softer from environmental degradation and poor oral absorption; therefore any carrier system for their oral delivery must have protection against enzymes and absorption  enhancing ability. Methods and Results: In this study, liposomes with different proportion of lipids (DPPC and DMPC) and cholesterol were prepared by film hydration method and converted to cochleates by hydrogel method with CaCl2 and MgCl2. Microscopically observation of structures was carried out by phase-contrast microscope and Scanning Electron Microscope (SEM). Physicochemical characteristics of these structures were evaluated by measuring size distribution  using with  laser light scattering technique, entrapment efficiency percentage, investigation of release profile, and stability of selected cochleates. HPLC method  was used for analytical evaluation of entrapped and released insulin.Best formulation of liposomes contains 70% of lipid and 30% of cholesterol. According to microscopic size distribution, cochleates with CaCl2 bridges were better. The size of vesicles was less than 6 µm. Insulin entrapment efficiency of cochleates with DPPC was more than DMPC type. Between 60-70% of encochleated insulin released after 2-4 hours in a buffer with pH 6.8. Conclusions:The results shows that cochleates can be suitable oral delivery systems for insulin

The Solid Lipid Nanoparticle (SLN) and Microemulsion Formulation Containing Parsol® 1789, 5000 and MCX: SPF and Physiochemucal Characteristics Evaluation .

Introduction: Sunlight has some benefits and also harms like as skin aging, photosensitivity, irregular hyper-pigmentation and skin cancer. So the use of sunscreen creams is proposed for protection and minimizes harmful adverse effects of sunlight. Solid lipid nanoparticles (SLN) and microemulsions (ME) are new drug delivery systems that are suitable for sunscreen delivery. Methods and Results: Different concentrations of lipid (Witepsol H35 and H15) and surfactants (Tween® 60 and Span® 60) were used as an ingredient for SLN formulations. Parsol® 1789, 5000 and MCX are used as active agents. SLN and ME were prepared by using High-shear Homogenization and ultrasound method. The particle size analysis, drug release، encapsulation studies and SPF evaluation of different SLN samples were examined. Stability of microemulsions was performed using a centrifuge. Also we used different concentrations of isopropyl myristate as a lipid, Tween® 80 and propylene glycol as a surfactant for preparing ME formulations. After adding sunscreen ingredients, particle size analysis and physical stability tests were studied. According to particle size analysis the best formulations for H35consists of 5% lipid, 15% surfactant with HLB=12 and for H15 consists of 5% lipid, 5% surfactant with HLB=11. Particle size of all of the formulations were less than 1µm, encapsulation efficacy was more than 70%. The maximum SPF was 38.75 and belongs to SLN formulation with lipid H35 and MCX (5%). According to turbidity and particle size the best formulation for ME was chosen. All of the ME formulations containing sunscreen agents have less than 500 nm particle size. Conclusions: Our result shows that SLN formulation is good carriers for sunscreen delivery. SLN particles act as a barrier for sunlight. So loading a UV absorbent like as MCX can improve sun screen ability of the formulation. Our result shows a SPF equal to 38.75. Also in SLN formulations the release of UV absorbent may be slower and has more duration in time. So the adverse effect may be lower and duration of action may be better. Finally we conclude that formulation of sunscreen in SLN base can improve sunscreen properties of products. Key words: . &nbsp

Dizajniranje i in vitro evaluacija transdermalnih flastera fentanila

The present research was designed to evaluate different matrix, drug-in-adhesive and reservoir formulations of fentanyl transdermal patches. The target was to design drug-in-adhesive patches (DIAPs); a full factorial design was used. Different types and amounts of liquid, pressure-sensitive adhesives (PSAs) were used and evaluated with respect to drug release and adhesive properties. A very simple but precise method, the simplified peel 180° test, was developed to measure and compare adhesive properties of transdermal patches. The results showed that release kinetics obeyed the square root of time or Higuchi model, indicating the diffusion controlled release mechanism. It was found that the amount of fentanyl needed for each 10 cm2 three-days DIAP should be 3.3 mg. The respective amounts for reservoir and matrix patches were 2.5 and 5 mg. It was concluded that acrylic PSAs showed the best adhesion and release properties.U radu su evaluirani različiti matriksni, adhezivni i spremišni ljekoviti oblici za transdermalnu primjenu fentanila. U dizajniranju adhezivnih flastera (DIAPs) uspotrebljene su različite vrste i količine tekućih adheziva osjetljivih na tlak (PSAs). Evaluirano je oslobađanje ljekovite tvari i adhezivna svojstva. Za mjerenje i usporedbu adhezivnih svojstava transdermalnih flastera razvijena je vrlo jednostavna, ali precizna "metoda ljuštenja". Rezultati su pokazali da kinetika oslobađanja slijedi kvadratni korijen vremena (Higuchijev model), ukazujući da se ljekovita tvar oslobađa difuzijom. Pokazalo se da je za svakih 10 cm2 DIAP-a za trodnevnu uporabu potrebno 3,3 mg fentanila. Ta količina je za spremišne i matriksne flastere iznosila 2,5, odnosno 5 mg. Najbolja adhezivna svojstva i oslobađanje fentanila bilo je iz akrilatnih pripravaka

Dizajniranje i in vitro evaluacija transdermalnih flastera fentanila

The present research was designed to evaluate different matrix, drug-in-adhesive and reservoir formulations of fentanyl transdermal patches. The target was to design drug-in-adhesive patches (DIAPs); a full factorial design was used. Different types and amounts of liquid, pressure-sensitive adhesives (PSAs) were used and evaluated with respect to drug release and adhesive properties. A very simple but precise method, the simplified peel 180° test, was developed to measure and compare adhesive properties of transdermal patches. The results showed that release kinetics obeyed the square root of time or Higuchi model, indicating the diffusion controlled release mechanism. It was found that the amount of fentanyl needed for each 10 cm2 three-days DIAP should be 3.3 mg. The respective amounts for reservoir and matrix patches were 2.5 and 5 mg. It was concluded that acrylic PSAs showed the best adhesion and release properties.U radu su evaluirani različiti matriksni, adhezivni i spremišni ljekoviti oblici za transdermalnu primjenu fentanila. U dizajniranju adhezivnih flastera (DIAPs) uspotrebljene su različite vrste i količine tekućih adheziva osjetljivih na tlak (PSAs). Evaluirano je oslobađanje ljekovite tvari i adhezivna svojstva. Za mjerenje i usporedbu adhezivnih svojstava transdermalnih flastera razvijena je vrlo jednostavna, ali precizna "metoda ljuštenja". Rezultati su pokazali da kinetika oslobađanja slijedi kvadratni korijen vremena (Higuchijev model), ukazujući da se ljekovita tvar oslobađa difuzijom. Pokazalo se da je za svakih 10 cm2 DIAP-a za trodnevnu uporabu potrebno 3,3 mg fentanila. Ta količina je za spremišne i matriksne flastere iznosila 2,5, odnosno 5 mg. Najbolja adhezivna svojstva i oslobađanje fentanila bilo je iz akrilatnih pripravaka

Development and Evaluation of a Novel Pellet-Based Tablet System for Potential Colon Delivery of Budesonide

Budesonide, a potent glucocorticoid, is used for the treatment of inflammatory bowel diseases. Current available oral formulations of budesonide have low efficacy against ulcerative colitis because of the premature drug release in the upper part of the gastrointestinal tract. In this paper a pH- and time-controlled colon-targeted pellet-based tablet of budesonide was established. Pellet cores were prepared by extrusion-spheronization method and further coated with xanthan gum (barrier layer), Eudragit NE30D and L30D55 combination (inner layer), and Eudragit FS30 (as enteric layer) sequentially to achieve the required release profile. The coated pellets then compressed into tablets using inert tabletting granules of Cellactose or Pearlitol. Release studies, performed in simulated gastric, intestinal, and colon pH were used in sequence to mimic the gastrointestinal transit. The influence of formulation variables like barrier layer thickness, inner layer composition, and enteric coat thickness on drug release were investigated and the coated pellets that contained 12% weight gain in xanthan gum layer, Eudragit L30D55 and Eudragit NE30D with a ratio of 3 : 7 in inner layer with 30% weight gain and 25% weight gain in Eudragit FS layer were found to protect the drug release in stomach and small intestine and 83.35 ± 2.4 of budesonide was released at 24 h. The drug release from the tablets prepared using 40% Cellactose 80 as tableting excipient was found to be closely similar to that of uncompressed pellets

Application of Response Surface Methodology for Optimization of Paracetamol Particles Formation by RESS Method

Ultrafine particles of paracetamol were produced by Rapid Expansion of Supercritical Solution (RESS). The experiments were conducted to investigate the effects of extraction temperature (313–353 K), extraction pressure (10–18 MPa), preexpansion temperature (363–403 K), and postexpansion temperature (273–323 K) on particles size and morphology of paracetamol particles. The characterization of the particles was determined by Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Liquid Chromatography/Mass Spectrometry (LC-MS) analysis. The average particle size of the original paracetamol was 20.8 μm, while the average particle size of paracetamol after nanonization via the RESS process was 0.46 μm depending on the experimental conditions used. Moreover, the morphology of the processed particles changed to spherical and regular while the virgin particles of paracetamol were needle-shape and irregular. Response surface methodology (RSM) was used to optimize the process parameters. The extraction temperature, 347 K; extraction pressure, 12 MPa; preexpansion temperature, 403 K; and postexpansion temperature, 322 K was found to be the optimum conditions to achieve the minimum average particle size of paracetamol

Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

Abstract: Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met) with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer

Pluronic based nano-delivery systems; Prospective warrior in war against cancer

Pluronic based nano-particulate systems are innovative platforms for delivery of anti-cancer agents. These systems due to their pharmacological properties and suitable physicochemical characteristics are great opportunity for development cancer therapeutics. This mini-review tries to provide a more detailed overview on the currently available pluronic based drug delivery systems. In the section 2, pharmacological characteristics of pluronic as a therapeutic polymer are assessed. In section 3, pluronic based formulations for undruggable payloads and surfaced modified targeted delivery systems are analyzed. The combinatorial pluronic based systems are summarized in section 4 and at last but not least the challenges and future prospective are discussed within section 5

Design and Characterization of Mesalamine Loaded Nanoparticles for Controlled Delivery System

Objective(s): Nanoparticles (NPs) are known for their specific accumulation in the inflamed tissues of the colon and thus allow a selective delivery to the site of inflammation with minimum adverse effects. The main objective of this work is to attain mesalamine loaded chitosan nanoparticles as a carrier for oral delivery. Methods: In this study, mesalamine loaded chitosan nanoparticles were prepared using an ionic gelation method. Experimental design Box-Behnken response surface methodology was used for the optimization of the nanoparticles. The nanoparticles size and gelation process of the polymeric nano-drug controlled release system depends on several variables including the concentration ratio of chitosan-TPP, concentration of mesalamine, concentration of chitosan solution and pH of the solution with optimum conditions of 2.3, 0.02 mg/ml, 0.1 mg/ml and 4.5, respectively. Results: The mean particle size of the synthesized nanoparticles was ranging from 53.9 to 322.8 nm using a dynamic light scattering (DLS) technique. Moreover, the morphology of the prepared nanoparticles was observed by scanning electron microscopy (SEM). Also, characterization of the chitosan-mesalamine nanoparticles was performed by FT-IR spectrophotometer for specifying the chemical structure of nanoparticles molecules and differential scanning calorimetry (DSC) for studying thermal behavior. Drug release profile and the amount of the loaded drug were also monitored by UV-Vis spectroscopy. Conclusions: Drug released showed that the release profile of mesalamine loaded nanoparticles was in a slow manner and no initial rapid release (burst effect) was illustrated

Preparation and Bioavailability Analysis of Ferrous Bis Alanine Chelate as a New Micronutrient for Treatment of Iron Deficiency Anemia

Purpose: One of the most nutritional disorders around the world is iron deficiency. A novel iron compound was synthesized by chelating ferrous ions with alanine for prevention and treatment of iron deficiency anemia. Methods: The newly synthesized compound was characterized both qualitatively and quantitatively by Fourier Transform Infrared (FT-IR) spectroscopy. The bioavailability of newly synthesized iron micronutrient was evaluated in four groups of Wistar rats. The group I was a negative control group and the other three groups received three different iron formulations. After 14 days, the blood samples were taken and analyzed accordingly. Results: Calculations showed that more than 91.8% of iron was incorporated in the chelate formulation. In vivo studies showed that serum iron, total iron binding capacity and hemoglobin concentrations were significantly increased in group IV, which received ferrous bis alanine chelate compared with the negative control group (p<0.05) and also group II, which received ferrous sulfate.7H2O (p<0.05). It indicates that the new formulation considerably improves the blood iron status compared with the conventional iron compounds. There were no significant differences (p<0.05) in the serum iron between group IV and group III, which received ferrous bis glycine. Conclusion: The results showed better bioavailability of ferrous bis alanine as a new micronutrient for treatment of iron deficiency anemia in comparison with ferrous sulfate. Ferrous bis alanine could be considered as a suitable supplement for prevention and treatment of iron deficiency anemia