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

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

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

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

Evaluation and optimization of chitosan derivatives-based gene delivery system via kidney epithelial cells

Purpose: Non-viral vectors have been widely proposed as safer alternatives to viral vectors, and cationic polymers have gained increasing attention because they can form self-assembly with DNA. Chitosan is also considered to be a good candidate for gene delivery systems, since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic potential. However, low solubility and transfection efficiency need to be overcome prior to clinical trial. In this work, we focus on alkyl modified chitosan which might be useful in DNA condensing and efficient gene delivery. Methods: N, N- Diethyl N- Methyl (DEMC) and N- Triethyl Chitosan (TEC) were synthesized from chitosan polymer. In order to optimize the polymers for gene delivery, we used FITC-dextran (FD). Then the optimized polymer concentrations were used for gene delivery. Fluorescent microscope was used, in order to evaluate the polymers’ efficiency for gene delivery to human embryonic kidney epithelial cells (HEK 293T). Results: This modification increased chitosan’s positive charge, thus these chitosan derivatives spontaneously formed complexes with FD, green fluorescence protein plasmid DNA (pEGFP), red fluorescence protein plasmid DNA (pJred) and fluorescent labeled miRNA. Results gained from fluorescent microscope showed that TEC and DEMC were able to transfer FD, DNA and miRNA (micro RNA) to HEK cell line. Conclusion: We conclude that these chitosan derivatives present suitable characteristics to be used as non-viral gene delivery vectors to epithelial cells

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

Development and Characterisation of Gastroretentive Solid Dosage Form Based on Melt Foaming

Dosage forms with increased gastric residence time are promising tools to increase bioavailability of drugs with narrow absorption window. Low-density floating formulations could avoid gastric emptying; therefore, sustained drug release can be achieved. Our aim was to develop a new technology to produce low-density floating formulations by melt foaming. Excipients were selected carefully, with the criteria of low gastric irritation, melting range below 70°C and well-known use in oral drug formulations. PEG 4000, Labrasol and stearic acid type 50 were used to create metronidazole dispersion which was foamed by air on atmospheric pressure using in-house developed apparatus at 53°C. Stearic acid was necessary to improve the foamability of the molten dispersion. Additionally, it reduced matrix erosion, thus prolonging drug dissolution and preserving hardness of the moulded foam. Labrasol as a liquid solubiliser can be used to increase drug release rate and drug solubility. Based on the SEM images, metronidazole in the molten foam remained in crystalline form. MicroCT scans with the electron microscopic images revealed that the foam has a closed-cell structure, where spherical voids have smooth inner wall, they are randomly dispersed, while adjacent voids often interconnected with each other. Drug release from all compositions followed Korsmeyer-Peppas kinetic model. Erosion of the matrix was the main mechanism of the release of metronidazole. Texture analysis confirmed that stearic acid plays a key role in preserving the integrity of the matrix during dissolution in acidic buffer. The technology creates low density and solid matrix system with micronsized air-filled voids