Pharmacological evaluation and safety of a donepezil patch.

Our aim was to assess the feasibility of transdermal delivery of donepezil and evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of donepezil patch and . Donepezil patches were applied to the skin of rabbits and humans for 7 days, then, the PK profiles were observed in a dose-dependent manner. Donepezil was continuously released from the patch for 7 days as compared to oral administration in hairless rats and rabbits.

Melt Amorphisation of Orlistat with Mesoporous Silica Using a Supercritical Carbon Dioxide: Effects of Pressure, Temperature, and Drug Loading Ratio and Comparison with Other Conventional Amorphisation Methods.

The aim of this work was to develop an amorphous orlistat-loaded mesoporus silica formulation using the melt-amorphisation by supercritical fluid (MA-SCF) and to investigate the effects of pressure and temperature on the pharmaceutical properties of the developed formulation. In addition, the effect of orlistat mass ratio to the mesoporus silica was also evaluated. The carbon dioxide was used as a supercritical fluid, and NeusilinUFL2 was selected as the mesoporous silica.

Pharmaceutical Characterization and In Vivo Evaluation of Orlistat Formulations Prepared by the Supercritical Melt-Adsorption Method Using Carbon Dioxide: Effects of Mesoporous Silica Type.

Orlistat, an anti-obesity drug, has two critical issues-the first is its low efficacy due to low water solubility and the second is side effects such as oily spotting due to its lipase inhibition. The present study was designed to propose a solution using a formulation with mesoporous silica to simultaneously overcome two issues. Orlistat was loaded onto mesoporous silica by the supercritical melt-adsorption (SCMA) method, using carbon dioxide (CO).

The Effects of Donepezil, an Acetylcholinesterase Inhibitor, on Impaired Learning and Memory in Rodents.

A previous study in humans demonstrated the sustained inhibitory effects of donepezil on acetylcholinesterase (AChE) activity; however, the effective concentration of donepezil in humans and animals is unclear. This study aimed to characterize the effective concentration of donepezil on AChE inhibition and impaired learning and memory in rodents. A pharmacokinetic study of donepezil showed a mean peak plasma concentration of donepezil after oral treatment (3 and 10 mg/kg) of approximately 1.

Cyclosporine Amicellar delivery system for dry eyes.

Background: The objectives of this study were to develop stable cyclosporine A (CsA) ophthalmic micelle solutions for dry-eye syndrome and evaluate their physicochemical properties and therapeutic efficacy.

Materials And Methods: CsA-micelle solutions (MS-CsA) were created by a simple method with Cremophor EL, ethanol, and phosphate buffer. We investigated the particle size, pH, and osmolarity.

In vivo gastric residence and gastroprotective effect of floating gastroretentive tablet of DA-9601, an extract of Artemisia asiatica, in beagle dogs.

Objective: DA-9601, an extract of Artemisia asiatica containing eupatilin and jaceosidin as active compounds, has been prescribed to treat gastritis in Asia. In recent times, sustained-release, floating gastroretentive (GR) tablets of DA-9601 are available on the market. In the present study, the physical properties and in vitro drug release profile, in vivo gastric residence time, and gastroprotective effect of GR tablet were compared to those of immediate release (IR) tablets of DA-9601.

Design of salmon calcitonin particles for nasal delivery using spray-drying and novel supercritical fluid-assisted spray-drying processes.

The overall aim of this study was to prepare a nasal powder formulation of salmon calcitonin (sCT) using an absorption enhancer to improve its bioavailability. In this work, powder formulations for nasal delivery of sCT were studied using various absorption enhancers and stabilizers. Powders were prepared by two different methods: conventional spray-drying (SD) and novel supercritical fluid-assisted spray-drying (SASD) to investigate the role of CO2 in the particle formation process.

Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent.

Objectives: The purpose of this study was to observe the pharmacokinetic behavior of newly synthesized biocompatible polymers based on polyhydroxyethylaspartamide (PHEA) to be used to coat an iron oxide core to make superparamagnetic iron oxide nanoparticles (SPION).

Materials And Methods: The isotopes [(14)C] and [(59)Fe] were used to label the polymer backbone (CLS) and iron oxide core (FLS), respectively. In addition, unradiolabeled cold superparamagnetic iron oxide nanoparticles (SPION/ULS) were synthesized to characterize particle size by dynamic light scattering, morphology by transmission electron microscopy, and in vivo magnetic resonance imaging (MRI).

Optimized formulation of solid self-microemulsifying sirolimus delivery systems.

Background: The aim of this study was to develop an optimized solid self-microemulsifying drug delivery system (SMEDDS) formulation for sirolimus to enhance its solubility, stability, and bioavailability.

Methods: Excipients used for enhancing the solubility and stability of sirolimus were screened. A phase-separation test, visual observation for emulsifying efficiency, and droplet size analysis were performed.

Supersaturatable formulations for the enhanced oral absorption of sirolimus.

The purpose of this study was to develop supersaturatable formulations for the enhanced solubility and oral absorption of sirolimus. Supersaturatable formulations of hydrophilic polymers and/or surfactants were screened by formulation screening, which is based on solvent casting. The solid dispersion particles in the optimized formulations were prepared by spray drying.

Solubilization of the poorly water soluble drug, telmisartan, using supercritical anti-solvent (SAS) process.

Telmisartan is a biopharmaceutical classification system (BCS) class II drug that has extremely low water solubility but is freely soluble in highly alkalized solutions. Few organic solvents can dissolve telmisartan. This solubility problem is the main obstacle achieving the desired bioavailability.

Enhancement of the dissolution rate and bioavailability of fenofibrate by a melt-adsorption method using supercritical carbon dioxide.

Background: The aim of this study was to enhance the bioavailability of fenofibrate, a poorly water-soluble drug, using a melt-adsorption method with supercritical CO(2).

Methods: Fenofibrate was loaded onto Neusilin(®) UFL2 at different weight ratios of fenofibrate to Neusilin UFL2 by melt-adsorption using supercritical CO(2). For comparison, fenofibrate-loaded Neusilin UFL2 was prepared by solvent evaporation and hot melt-adsorption methods.

Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process.

Background: The aim of this study was to improve the physicochemical properties and bioavailability of poorly water-soluble sirolimus via preparation of a solid dispersion of nanoparticles using a supercritical antisolvent (SAS) process.

Methods: First, excipients for enhancing the stability and solubility of sirolimus were screened. Second, using the SAS process, solid dispersions of sirolimus-polyvinylpyrrolidone (PVP) K30 nanoparticles were prepared with or without surfactants such as sodium lauryl sulfate (SLS), tocopheryl propylene glycol succinate, Sucroester 15, Gelucire 50/13, and Myrj 52.

Comparative study of telmisartan tablets prepared via the wet granulation method and pritor™ prepared using the spray-drying method.

The wet granulation method was successfully used to manufacture amorphous telmisartan tablets (CNU) for comparison with the spray-drying method, used for Pritor™. Drug crystallinity in the tablet was characterized using differential scanning calorimetry and powder X-ray diffraction, and pharmaceutical properties of the tablets such as hardness, friability, water absorption, and in vitro dissolution in pH 1.2, 4.

pH-independent sustained release matrix tablet containing doxazosin mesylate: effect of citric acid.

The aim of this study was to develop a pH-independent sustained release matrix tablets of doxazosin mesylate. The matrix tablets were prepared by direct compression technique using polyethylene oxide, sodium alginate and citric acid as a pH modifier. Formulations were evaluated for an in vitro drug release study, erosion study, and the microenvironmental pH was studied using the pH indicator methyl red.

Solid-state carbon NMR characterization and investigation of intrinsic dissolution behavior of fluconazole polymorphs, anhydrate forms I and II.

Solid-state (13)C nuclear magnetic resonance ((13)C-SSNMR) revealed significant differences in the chemical shift of specific carbon atoms between two fluconazole polymorphs, reflecting a change in molecular conformation. A single resonance signal without splitting was observed in the spectrum of anhydrate form II, while the spectrum of anhydrate form I showed signals with splitting, indicating the presence of two dissimilar molecular conformations in the unit cell of anhydrate form I. The Fourier transform infrared (FT-IR) and Raman spectra associated with the triazole group, the 2,4-difluorobenzyl group, and the propane backbone provided also evidence of structural differences between forms I and II accompanying with (13)C-SSNMR.

Quantitative determination of sirolimus in dog blood using liquid chromatography-tandem mass spectrometry, and its applications to pharmacokinetic studies.

A rapid, sensitive method of detecting sirolimus in blood was developed and applied in pharmacokinetic studies employing deionized water for hemolysis and a weakly basic mobile phase to enhance chromatographic peak intensity. Dog blood samples were processed via liquid-liquid extraction and the amounts of sirolimus and tacrolimus, an internal standard, were quantified by LC-MS/MS. Specificity, the lower limit of quantification, linearity, accuracy, precision, dilution, recovery, matrix effects, robustness and stability were within the acceptable range for assay validation.

Preparation and pharmaceutical characterization of amorphous cefdinir using spray-drying and SAS-process.

The aim of this study was to investigate the effects of micronization and amorphorization of cefdinir on solubility and dissolution rate. The amorphous samples were prepared by spray-drying (SD) and supercritical anti-solvent (SAS) process, respectively and their amorphous natures were confirmed by DSC, PXRD and FT-IR. Thermal gravimetric analysis was performed by TGA.

Enhanced dissolution of megestrol acetate microcrystals prepared by antisolvent precipitation process using hydrophilic additives.

Microcrystals of megestrol acetate (MA), a poorly water-soluble drug, were successfully prepared using an antisolvent precipitation technique for improving the dissolution rate. The effective hydrophilic polymers and surfactants used were screened for their abilities to produce smaller particle sizes. Raw micronized MA and processed MA microcrystals were ranked by the Student-Newman-Keuls test in order of increasing particle size and SPAN values as follows: processed MA microcrystals in the presence of polymer and surfactant (mean diameter 1048nm) View Article and Find Full Text PDF

Pharmacokinetic and bioequivalence study of itopride HCl in healthy volunteers.

In the present study two different formulations containing 50 mg itopride HCl (N-[4-12-(dimethylamino)ethoxylbenzyl]-3,4-dimethoxybenzamide HCl, CAS 122898-67-3) were compared in 28 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, crossover design in 28 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 24 h.

Design of pH-independent extended release matrix tablets of minocycline hydrochloride for the treatment of dementia.

The aim of this study was to develop a pH-independent extended release matrix tablet of minocycline HCl for the treatment of dementia. The matrix tablets were prepared by wet granulation technique using Eudragit L and S as release modifiers at different w/w ratios (1:0, 1:1 and 0:1) and PEO as a matrix former. In the case of the matrix tablet without any release modifiers, the drug release rate at pH 1.