Integration of lornoxicam nanocrystals into hydroxypropyl methylcellulose-based sustained release matrix to form a novel biphasic release system.

The study aims to (a) enhance the solubility of a poorly soluble drug by optimization of nanocrystal formulation using the top-down approach and (b) modify the release profile of this drug, which exhibits a short elimination half-life, by the integration of a fast-release phase containing the optimized nanocrystals and a sustained-release phase in a compression-coated tablet. Nanocrystals of the model drug (lornoxicam; LNX) was prepared by simultaneous application of jet-milling and ball-milling techniques. Investigation of the precipitation inhibition capacity, thermal property, and interaction of different polymers with the drug revealed polyvinyl pyrrolidone K30 (PVP) as the most effective stabilizer for nanocrystals.

Effect of surfactant on the in vitro dissolution and the oral bioavailability of a weakly basic drug from an amorphous solid dispersion.

This study aimed to investigate the effect of a surfactant on the liquid-liquid phase separation, dissolution, diffusion, and the oral bioavailability of a weakly basic drug (l-tetrahydropalmatine; l-THP) from an amorphous solid dispersion (ASD). The carrier used in the ASD was optimized by the application of casting film, solvent shift, and pH shift methods. The interaction between the optimized carrier (HPMCP) and l-THP was then evaluated by Fourier transform-infrared spectroscopy and powder X-ray diffraction.

Data on optimization and drug release kinetics of nanostructured lipid carriers containing ondansetron hydrochloride prepared by cold high-pressure homogenization method.

Nanostructured lipid carriers (NLCs), the second generation of lipid nanoparticles could enhance the drug loading capacity and minimize the drug expulsion during storage [1,2]. They are prepared from mixtures of solid and liquid lipids [3,4]. The article described the data for the preparation, optimization, and drug release studies of NLCs loaded with ondansetron hydrochloride (OSH), a water-soluble drug.

Preparation of an oil suspension containing ondansetron hydrochloride as a sustained release parenteral formulation.

Ondansetron hydrochloride (ODS) is a selective 5-hydroxytryptamine type 3 antagonist for nausea and emesis prevention in neoplastic patients. To reduce dosing frequency and side effects and improve patient compliance, a sustained release parenteral formulation of ODS was developed. Microparticles of methylcellulose (MC) and ODS were prepared using the spray-drying method and suspended in oils to form oil suspensions.

Preparation of Ondansetron Hydrochloride-Loaded Nanostructured Lipid Carriers Using Solvent Injection Method for Enhancement of Pharmacokinetic Properties.

Purpose: This study aimed to incorporate ondansetron hydrochloride (ODS), a water-soluble drug into nanostructured lipid carriers (NLCs) to improve the pharmacokinetic properties of the drug.

Methods: NLCs were produced by solvent injection method. Various parameters of formulation and process were assessed to enhance the drug incorporation into NLCs.

Formulation and biopharmaceutical evaluation of supersaturatable self-nanoemulsifying drug delivery systems containing silymarin.

The first objective of this study was to optimize a supersaturatable self-nanoemulsifying drug delivery system (S-SNEDDS) containing silymarin through the investigation of the single and synergistic effect of either SNEDDS or a precipitation inhibitor on dissolution efficiency (DE) of silymarin. The bioavailability and hepatoprotective activity of S-SNEDDS were then compared to those of a branded product (Legalon®, Meda). SNEDDS containing silymarin was developed by titration technique, and Poloxamer 407 was selected as the optimal precipitation inhibitor by using casting film and solvent-shift method.

Development of solidified self-microemulsifying drug delivery systems containing l-tetrahydropalmatine: Design of experiment approach and bioavailability comparison.

The study first aimed to apply a design of experiment (DoE) approach to investigate the influences of excipients on the properties of liquid self-microemulsifying drug delivery system (SMEDDS) and SMEDDS loaded in the pellet (pellet-SMEDDS) containing l-tetrahydropalmatine (l-THP). Another aim of the study was to compare the bioavailability of l-THP suspension, liquid SMEDDS and pellet-SMEDDS in the rabbit model. By using Central Composite Face design (CCF), the optimum ratio of Capryol 90, and S `(Cremophor RH 40: Transcutol HP) in the formulation of SMEDDS was determined.

Topical delivery of dexamethasone acetate from hydrogel containing nanostructured liquid carriers and the drug.

The potential of hydrogel containing nanostructured lipid carriers (NLC) to enhance the skin permeation rate and skin deposition of dexamethasone acetate (DEA) was investigated. The particle size of obtained NLCs was around 224.4 nm.

Formulation and biopharmaceutical evaluation of a transdermal patch containing aceclofenac.

To reduce the adverse effects of aceclofenac that accompanied with oral administration of this drug, transdermal patches in the form of drug-in-adhesive (DIA) patches, containing aceclofenac, were formulated. The effect of formulation factors on the skin permeation of the drug and physical properties of the patch were evaluated using excised rat skins. The optimized patch contained 12 % aceclofenac and 20 % lauryl alcohol in DT-2852 as a pressure-sensitive adhesive.

Preparation and evaluation of sustained-release doxazosin mesylate pellets.

Doxazosin mesylate (DXM) sustained release pellets were prepared by an extrusion-spheronization and fluid-bed coating technique. The core pellets containing DXM were prepared by extrusion-spheronization technique, and coated by a fluid-bed coater to control the release of DXM. The factors affecting to properties of pellets, such as diluent content, type and coating level of coating agents and plasticizers were studied in the present study.

Preparation and evaluation of raloxifene-loaded solid dispersion nanoparticle by spray-drying technique without an organic solvent.

The aim of this study was to improve the physicochemical properties and bioavailability of a poorly water-soluble drug, raloxifene by solid dispersion (SD) nanoparticles using the spray-drying technique. These spray-dried SD nanoparticles were prepared with raloxifene (RXF), polyvinylpyrrolidone (PVP) and Tween 20 in water. Reconstitution of optimized RXF-loaded SD nanoparticles in pH 1.

Preparation of highly porous gastroretentive metformin tablets using a sublimation method.

The present investigation is aimed to formulate floating gastroretentive tablets containing metformin using a sublimation material. In this study, the release of the drug from a matrix tablet was highly dependent on the polymer concentrations. In all formulations, initial rapid drug release was observed, possibly due to the properties of the drug and polymer.

Preparation and valuation of a topical solution containing eutectic mixture of itraconazole and phenol.

The purposes of this study were to prepare a topical solution containing itraconazole (ITR)-phenol eutectic mixture and to evaluate its ex vivo skin permeation, in vivo deposition and in vivo irritation. The eutectic mixture was prepared by agitating ITR and phenol (at a weight ratio of 1:1) together at room temperature. The effects of additives on the skin permeation of ITR were evaluated using excised hairless mouse skin.

Fabrication and evaluation of pH-modulated solid dispersion for telmisartan by spray-drying technique.

The present study was undertaken to overcome the problems associated with solubility, dissolution and oral bioavailability of a poorly water-soluble ionizable drug, telmisartan (TMS). For these purposes, a solubility test was carried to select the appropriate formulation composition from various carriers and alkalizers. Solid dispersions (SDs) of TMS were prepared at different drug-to-carrier ratios by the spray-drying technique, and were characterized by dissolution and aqueous solubility studies.

Phase behavior of itraconazole-phenol mixtures and its pharmaceutical applications.

The aims of this study were to examine the phase behavior of itraconazole-phenol mixtures and assess the feasibility of topical formulations of itraconazole using eutectic mixture systems. Itraconazole-phenol eutectic mixtures were characterized using differential scanning calorimetry, Fourier transform infrared spectroscopy, (1)H-nuclear magnetic resonance, and powder X-ray diffractometry. The skin permeation rates of itraconazole-phenol eutectic formulations were determined using Franz diffusion cells fitted with excised hairless mouse skins.

Self-assembled glycol chitosan nanogels containing palmityl-acylated exendin-4 peptide as a long-acting anti-diabetic inhalation system.

Inhalable deoxycholic acid-modified glycol chitosan (DOCA-GC) nanogels containing palmityl acylated exendin-4 (Ex4-C16) were prepared by self-assembly and characterized physicochemically. The lung deposition of DOCA-GC nanogels was monitored using an infrared imaging system, and the hypoglycemia caused by Ex4-C16-loaded DOCA-GC nanogels was evaluated after pulmonary administration in type 2 diabetic db/db mice. The cytotoxicities and lung histologies induced by DOCA-GC nanogels were examined in human lung epithelial cells (A549 and Calu-3) and db/db mice, respectively.

Pulmonary administered palmitic-acid modified exendin-4 peptide prolongs hypoglycemia in type 2 diabetic db/db mice.

Hypoglycemia caused by palmitic-acid modified exendin-4 (Pal-Ex4) administered via the pulmonary route was evaluated and compared with that caused by native Ex4. Pal-Ex4 and Ex4 in solution (each 50 μl) were administered using a microsprayer directly into the trachea of type 2 diabetic db/db mice at 75 or 150 nmol/kg. The lung depositions of Cy5.

Physicochemical, pharmacokinetic and pharmacodynamic evaluations of novel ternary solid dispersion of rebamipide with poloxamer 407.

This study was conducted primarily to improve the solubility of rebamipide, a poorly water-soluble anti-ulcer drug, using novel ternary solid dispersion (SD) systems and secondly to evaluate the effect of solubility enhancement on its pharmacokinetic (PK) and pharmacodynamic (PD) profile. After dissolving the three components in aqueous medium, ternary SD containing the drug, sodium hydroxide (NaOH) and PVP-VA 64 was achieved by spray drying method, which was used as primary SD. Poloxamer 407, a surfactant polymer, was incorporated in this primary SD by four different methods: co-grinding, physical mixing, melting or spray drying.

Energy-independent intracellular gene delivery mediated by polymeric biomimetics of cell-penetrating peptides.

Efficient gene transfer into mammalian cells mediated by small molecular amphiphile-polymer conjugates, bile acid-polyethylenimine (BA-PEI), is demonstrated, opening an efficient transport route for genetic materials across the cell membrane. This process occurs without the aid of endocytosis or other energy-consuming processes, thus mimicking macromolecular transduction by cell-penetrating peptides. The exposure of a hydrophilic face of the amphiphilic BA moiety on the surface of BA-PEI/DNA complex that mediates direct contact of the BA molecules to the cell surface seems to play an important role in the endocytosis- and energy-independent internalization process.

Roles of MgO release from polyethylene glycol 6000-based solid dispersions on microenvironmental pH, enhanced dissolution and reduced gastrointestinal damage of telmisartan.

The roles of magnesium oxide (MgO) release from solid dispersions (SDs) in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and water were investigated to elucidate the enhanced dissolution and reduced intestinal damages of telmisartan as a model drug. The polyethylene glycol 6000 (PEG 6000) was used to prepare the SDs. Three SDs were prepared: SD1 (PEG, MgO, TEL), SD2 (PEG 6000, TEL), SD3 (MgO, TEL).

Immediate release of ibuprofen from Fujicalin®-based fast-dissolving self-emulsifying tablets.

Background: Drug release from a solid form of self-emulsifying drug delivery system (SEDDS) has greatly been limited due to strong adsorption and physical interaction with carriers. To facilitate drug release process in the stomach, an acid-soluble powderizing carrier, Fujicalin(®) was evaluated together with different disintegrants and hydrophilic lubricants.

Method: Immediate-release self-emulsifying tablets (IR-SETs) of ibuprofen (IBU) was prepared with solidified SEDDS of IBU, various disintegrants, and lubricants, and drug release was evaluated to develop IR-SET that can release IBU with a similar IBU release rate to that obtained with liquid SEDDS.

Preparation and evaluation of Cremophor-free paclitaxel solid dispersion by a supercritical antisolvent process.

Objectives: To avoid the major adverse effects induced by Cremophor EL formulated in the commercial paclitaxel products of Taxol.

Methods: An injectable paclitaxel solid dispersion free of Cremophor was prepared by a supercritical antisolvent process and then was fully characterized and investigated with regard to its short-term and long-term stability. Pharmacokinetics in rats was also evaluated compared with the commercial product.

Physicochemical stability, pharmacokinetic, and biodistribution evaluation of paclitaxel solid dispersion prepared using supercritical antisolvent process.

Aim: To investigate the physicochemical stability, pharmacokinetics (PK), and biodistribution of paclitaxel (PTX) from paclitaxel solid dispersion (PSD) prepared by supercritical antisolvent (SAS) process.

Methods: Physicochemical stability was performed in accelerated (40°C 70 ± 5% RH) and stress (60°C) storage conditions for a period of 6 months and 4 weeks, respectively. PK and biodistribution studies were performed in rats following i.

Antitumor efficacy of solid dispersion of paclitaxel prepared by supercritical antisolvent process in human mammary tumor xenografts.

The efficacy of intravenous chemotherapy for breast cancer has been improving with newer agents. However, the fractional improvements in breast cancer progression-free survival were quite modest and these small gains are obtained at the cost of significant toxicity. To address this problem, paclitaxel solid dispersion (PSD), a Cremophor EL-free formulation prepared by supercritical antisolvent process using hydrophilic polymers as carrier, was developed to avoid Cremophor EL-associated toxicities in Taxol(®).

Effect of electrokinetic stabilizers on the physicochemical properties of propofol emulsions.

The aims of the present study were to elucidate the potential mechanism of propofol emulsion destabilization following the addition of lidocaine, and to evaluate the effects of various electrokinetic stabilizers on the physicochemical properties of lidocaine-propofol emulsions. The assessments included pH observations and determination of the maximum globule diameter (MGD) and zeta potential (ZP). The MGD of propofol emulsions increased up to several tens mum following the addition of 50 mg of lidocaine to 200mg of propofol, and the proposed destabilization mechanism involves localization of protonated lidocaine molecules between lecithin molecules in propofol emulsions, which consequently leads to increased ZP.