Ex-vivoand in-vitro assessment of mucoadhesive patches containing the gel-forming polysaccharide psyllium for buccal delivery of chlorhexidine base.

The aim of the present study was to evaluate the gel-forming polysaccharide psyllium in the preparation of mucoadhesive patches for the controlled release of chlorhexidine (CHX) to treat pathologies in the oral cavity, using the casting-solvent evaporation technique. A number of different film-forming semi-synthetic polymers, such as sodium carboxymethyl cellulose (SCMC) and hydroxypropylmethyl cellulose (HPMC) were evaluated for comparison. The patch formulations were characterized in terms of drug content, morphology surface, swelling and mucoadhesive properties, microbiology inhibition assay and in vitro release tests.

Image analysis of lutrol/gelucire/olanzapine microspheres prepared by ultrasound-assisted spray congealing.

Nine systems were prepared containing Gelucire 50/13 and various amounts (9-18-36-45% w/w) of Lutrol F68 and F127 in the presence and in the absence of 10% w/w of olanzapine and formulated as a solid dispersion in the form of microspheres by ultrasound (US)-assisted spray congealing. Thermal analysis, using differential scanning calorimetry (DSC) and thermomicroscopy (HSM), suggested the presence of particles of reduced size of olanzapine precipitated inside the microspheres. The microspheres were also studied by means of electron microscopy (SEM) for their shape and aspect, by some image analysis parameters (fractal dimension) and using Energy-dispersive X-ray (X-EDS) and micro-Raman spectroscopy to qualitatively evaluate the composition of different points of the surface.

Design of olanzapine/lutrol solid dispersions of improved stability and performances.

Eleven solid dispersions containing olanzapine, with carriers of different composition (Lutrol® F68, Lutrol® F127, Gelucire® 44/14), were prepared and examined by thermal (differential scanning calorimetry (DSC); thermomicroscopy (HSM)) and X-ray diffraction (XRD) analysis, both as fresh or aged (one year) samples. Drug and carriers were preliminarily selected in order to avoid problems related to the aging of the formulation, according to the solubility parameters of carriers and drug. These parameters make it possible to predict the low solubility of olanzapine in the carriers (alone or in mixtures).

Olanzapine solvates.

Olanzapine was crystallized from 12 organic solvents alone or in mixture, by cooling in the freezer, by slow evaporation of the solvent, or by suspending olanzapine powder for some time in the solvent. All the samples thus obtained were examined by thermal analysis (differential scanning calorimetry-DSC and thermogravimetry-TG) to certify the formation of a solvate, the presence of polymorph (form 1 or 2) in the desolvated olanzapine, comparing the different profile of the thermograms, and to calculate the stoichiometry of the possible solvate. According to the DSC thermogram, the solvents can be divided into four classes: those that do not form solvates and leave olanzapine form 1 (ethyl acetate, toluene, diethyl ether, and acetone); those that form solvate and leave form 1 of olanzapine after desolvation (methanol, 1- and 2-propanol); those that after desolvation of the solvate show a polymorph transition in the thermogram indicating the presence of form 2 of olanzapine (ethanol); other solvents (tetrahydrofuran, chloroform, acetonitrile) give solvate thermograms, where this last thermal trace is only poorly evident.

Mucoadhesive multiparticulate patch for the intrabuccal controlled delivery of lidocaine.

The aim of the present study was to prepare and evaluate patches for the controlled release of lidocaine in the oral cavity. Mucoadhesive buccal patches, containing 8 mg/cm(2) lidocaine base, were formulated and developed by solvent casting method technique, using a number of different bio-adhesive and film-forming semi-synthetic and synthetic polymers (Carbopol, Poloxamer, different type Methocel) and plasticizers (PEG 400, triethyl citrate); the patches were evaluated for bioadhesion, in vitro drug release and permeation using a modified Franz diffusion cell. A lidocaine/Compritol solid dispersion in the form of microspheres, embedded inside the patch, alone or together with free lidocaine, was also examined to prolong the drug release.

Diclofenac salts, part 7: are the pharmaceutical salts with aliphatic amines stable?

Eight cyclic aliphatic amines, pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz), and the N-hydroxyethyl (HE) analogues, were employed to prepare a salt with acidic diclofenac (D). These salts were examined by thermal [differential scanning calorimetry (DSC), thermogravimetric analysis, and hot-stage microscopy (HSM)] and spectroscopic [Fourier transform infrared (FTIR), Raman, (1) H NMR, and ultraviolet] analysis. The results show the thermal instability of these salts: the thermal dissociation leaves the starting acidic D, evidenced by the FTIR and Raman spectra inside the molten mass of the salts with M and HEM.

Diclofenac Salts, VIII. Effect of the Counterions on the Permeation through Porcine Membrane from Aqueous Saturated Solutions.

The following bases: monoethylamine (EtA), diethylamine (DEtA), triethylamine (TEtA), monoethanolamine (MEA), diethanolamine (DEA), triethanolamine (TEA), pyrrolidine (Py), piperidine (Pp), morpholine (M), piperazine (Pz) and their N-2-hydroxyethyl (HE) analogs were employed to prepare 14 diclofenac salts. The salts were re-crystallized from water in order to obtain forms that are stable in the presence of water. Vertical Franz-type cells with a diffusional surface area of 9.

Diclofenac salts, part 6: release from lipid microspheres.

The release of diclofenac (20%, w/w) was studied from lipidic solid dispersions using three different chemical forms (acid, sodium salt, and pyrrolidine ethanol salt) and two different lipid carriers (Compritol 888 ATO or Carnauba wax) either free or together with varying amounts (10%-30%, w/w) of stearic acid. Microspheres were prepared by ultrasound-assisted atomization of the molten dispersions and analyzed by scanning electron microscopy, differential scanning calorimetry, and hot stage microscopy. The effects of different formulations on the resulting drug release profiles as a function of pH were studied and the results were discussed.

Mucoadhesive gels designed for the controlled release of chlorhexidine in the oral cavity.

This study describes the in vitro/ex vivo buccal release of chlorhexidine (CHX) from nine mucoadhesive aqueous gels, as well as their physicochemical and mucoadhesive properties: CHX was present at a constant 1% w/v concentration in the chemical form of digluconate salt. The mucoadhesive/gel forming materials were carboxymethyl- (CMC), hydroxypropylmethyl- (HPMC) and hydroxypropyl- (HPC) cellulose, alone (3% w/w) or in binary mixtures (5% w/w); gels were tested for their mucoadhesion using the mucin method at 1, 2 and 3% w/w concentrations. CHX release from different formulations was assessed using a USP method and newly developed apparatus, combining release/permeation process in which porcine mucosa was placed in a Franz cell.

Theophylline-loaded compritol microspheres prepared by ultrasound-assisted atomization.

Nine solid dispersions were prepared by the melting method in the form of particles containing theophylline at 10%, 20%, and 30% (w/w) in three Compritols (Compritol 888 ATO, HD5 ATO, E ATO) to compare their efficiency in controlling theophylline release. After solidification the mass was ground and granules were evaluated by thermal [differential scanning calorimetry, hot stage microscopy (HSM)] and spectroscopic [Fourier transform infrared (FTIR), Raman, X-ray powder diffraction (XRD)] analysis and the solubility parameters. Another nine samples of the same composition were obtained as microspheres by ultrasound-assisted (US) atomization.

Bimodal release of olanzapine from lipid microspheres.

Olanzapine was formulated as 10% (w/w) mixture with cutina to which stearic acid was added, ranging from 10% to 90% (w/w) of the total mass to control the drug release. The molten mixtures were processed by ultrasound-assisted spray-congealing technique, obtaining solid microspheres. The drug is stable under these conditions and only a partial miscibility in the solid state was observed by DSC between the two fatty materials with two separated melting endotherms in the thermograms: this can be due to the presence of two phases inside the solid dispersion.

Diclofenac Salts. V. Examples of Polymorphism among Diclofenac Salts with Alkyl-hydroxy Amines Studied by DSC and HSM.

Nine diclofenac salts prepared with alkyl-hydroxy amines were analyzed for their properties to form polymorphs by DSC and HSM techniques. Thermograms of the forms prepared from water or acetone are different in most cases, suggesting frequent examples of polymorphism among these salts. Polymorph transition can be better highlighted when analysis is carried out by thermo-microscopy, which in most cases made it possible to observe the processes of melting of the metastable form and re-crystallization of the stable one.

Synthesis, structural characterization and antibacterial activity of novel 7beta-{[3-(substituted phenyl)-2-propenoyl]amino}-3-[(2,5-dihydro-6-hydroxy-2-methyl)-5-oxo-cis-triazin-3-yl]-thiomethyl-cefalosporins.

A series of 3-[(2,5-dihydro-6-hydroxy-2-methyl)-5-oxo-cis-triazin-3-yl]-thiomethyl-cefalosporins with various 3-phenyl-2-propenoyl substituted groups at the 7beta-position were synthesized, structurally characterized and evaluated for antibacterial activity in vitro. To prepare these derivatives by the Vilsmeier's reagent method, it was necessary to carefully control the reaction conditions in order to avoid the formation of the biologically inactive alpha epimer. The NMR studies showed that the 3-phenyl-2-propenoyl moiety has little effect on chemical shifts of cephem nucleus protons and carbon atoms.

Raman and thermal analysis of indomethacin/PVP solid dispersion enteric microparticles.

Indomethacin (IMC) and three types of poly-(vinylpyrrolidone) (PVP 12PF, PVP K30 and PVP K90) were studied in the form of solid dispersion, prepared with the solvent evaporation method, by spectroscopic (Raman, FT-IR, X-ray diffraction), thermal (differential scanning calorimetry, thermogravimetry, hot-stage microscopy), fractal and image analysis. Raman and FT-IR micro-spectroscopy indicated the occurrence of drug/polymer interaction and the presence of an amorphous form of IMC, as also resulting from X-ray diffractometry. Hot-stage microscopy suggested that the interaction between IMC and the polymer occurring on heating of a physical mixture, is common to other acidic compounds and causes a depression of the temperature of the appearance of a molten phase.

ATR/Raman and fractal characterization of HPBCD/progesterone complex solid particles.

Purpose: Characterization of hydroxypropyl-beta-cyclodextrin/progesterone (HPBCD/P) complex solid particles obtained from an aqueous solution, by three different technological processes, with the aim of preparing ready-to-dissolve powders for injectable as well as solid oral formulations in progestinic therapy.

Methods: HPBCD/P complex in the 2:1 molar ratio was prepared in aqueous solution and obtained as dry solid particles by freeze-drying, by spray-drying and by fluid-bed evaporation of the solvent. The particles were characterized by mu-FT-IR, mu-Raman and X-ray spectroscopy, by thermal analysis (differential scanning calorimetry-DSC and thermogravimetry-TGA), by Karl Fischer (KF) titration, by image and fractal analysis and by BET specific surface area analysis.

Control of transdermal permeation of hydrocortisone acetate from hydrophilic and lipophilic formulations.

The purpose of this research was the preparation of four formulations containing hydrocortisone acetate (HCA) for topical application, including two aqueous systems (hydrophilic microemulsion and aqueous gel) and two systems with dominant hydrophobicity (hydrophobic microemulsion and ointment). The formulations were tested for the release and permeation of HCA across an animal membrane. The release of HCA was found comparable for the four systems.

Fast dispersible/slow releasing ibuprofen tablets.

Eight formulations were developed containing ibuprofen in the form of orally disintegrating tablets. To prevent bitter taste and side effects of the drug, the drug was associated with Phospholipon 80H, a saturated lecithin, by wet granulation. The granules were then coated using different film forming agents (Kollicoat SR 30, Amprac 01, Kollidon 90F, Eudragit RD 100) obtaining four lots 1-4.

Effect of vehicles on topical application of aloe vera and arnica montana components.

In this study two types of gels and microemulsions are investigated for their ability to dissolve, release, and induce the permeation of helenalin, a flavonoid responsible for the anti-inflammatory activity of arnica montana extract, and aloin, an anthrone-C-glucosyls with antibacterial activity present in aloe vera extract. The release of these agents from each vehicle was followed by HPLC, and transcutaneous permeation was examined using a modified Franz cell and a porcine skin membrane. The study showed that a microemulsion can be a good vehicle to increase the permeation of helenalin, while the gel formulation, containing Sepigel 305, proved able to reduce the release and permeation of aloin, with a consequent activity limited to the surface of application, without any permeation.

Solid state characterization of progesterone in a freeze dried 1:2 progesterone/HPBCD mixture.

Progesterone rapidly dissolves in an aqueous solution containing hydroxypropyl-beta-cyclodextrin (HPBCD) at 1:2 molar ratio, forming a soluble inclusion complex. After filtration and freeze-drying of the final solution, the final powder was examined by SEM, DSC, TGA, XRD, Raman, and FTIR spectroscopy. Experimental results confirm that an inclusion complex exists in the solid state and possible structure of the complex is briefly discussed.

Study of the interaction between oxygen and bile salts.

The interaction between molecular oxygen and bile salts, previously observed using chemiluminescence techniques, is studied in this paper by electrochemical techniques to further highlight the nature of the interaction. A shift of half-wave potential of the first polarographic wave for the reduction of molecular oxygen was observed in solutions in the presence of bile salts. The shift could be related to different phenomena, such as adsorption of bile salt molecules on the mercury electrode, irreversibility of the oxygen reduction reaction, pH of the solution.

Ex vivo study of transdermal permeation of four diclofenac salts from different vehicles.

The ex vivo permeation of diclofenac was studied using four different salts (sodium, potassium, diethylamine, and epolamine) dissolved in four different solvents (water, propylene glycol (PG), Transcutol, and oleic acid (OA)) as donor phases through a human skin membrane. The four salts show different solubility values and different behavior in the four solvents, which are also permeation enhancers and this fact further is connected to the permeation results. The same order of magnitude of fluxes through the membrane as those previously reported for acidic diclofenac released from buffer solutions of pH >7 were found, taking into account differences originated by different membranes and other parameters tested in the experiments.

13C NMR spectroscopy of some third-generation cephalosporins, their synthetic intermediaries and reaction byproducts.

(13)C NMR spectroscopic data for 25 cephalosporin derivatives were assigned by combination of one- and two-dimensional experiments. The effect of the substitution at C-3, C-7 and C-4 acid group positions on the chemical shifts of the cephem nucleus is discussed.

Enhanced release of indomethacin from Pvp/stearic acid microcapsules prepared coupling Co-freeze-drying and ultrasound assisted spray-congealing process.

Purpose: Fast releasing indomethacin microparticles were prepared encapsulating co-freeze-dried indomethacin/poly(vinylpyrrolidone) particles (IMC/PVP) into molten stearic acid (SA), by means of a ultrasonic spray-congealing technique.

Materials And Methods: IMC particles were suspended in a PVP aqueous solution and the system was then freeze-dried. A suspension was prepared from the co-freeze dried IMC/PVP powder into molten SA that was then atomized into small droplets using ultrasound.

Diclofenac salts. III. Alkaline and earth alkaline salts.

Diclofenac salts containing the alkaline and two earth alkaline cations have been prepared and characterized by scanning electron microscopy (SEM) and EDAX spectroscopy; and by thermal and thermogravimetric analysis (TGA): all of them crystallize as hydrate when precipitated from water. The salts dehydrate at room temperature and more easily on heating, but recovery the hydration, when placed in a humid environment. X-ray diffraction spectra suggest that on dehydration new peaks appear on diffractograms and the lattice of the salts partially looses crystallinity.

Interactions between different selenium compounds and zinc, cadmium and mercury.

In this paper, we present a polarographic study of systems containing different inorganic and organic selenium compounds (sodium selenite, sodium selenate, seleno-methionine and seleno-urea) and metal ions (Zn2+, Cd2+ Hg2+) of the 12th group of elements in the periodic table. While zinc is a trace element known to be essential for plants and animals, cadmium and mercury are exogenous elements and are harmful pollutants that accumulate during aging; selenium is also recognized as an important micronutrient and is sometimes added to the diet. Experiments investigating the interactions were carried out using polarographic techniques in unbuffered systems.