Composites Containing Nanohydroxyapatites and a Stable TEMPO Radical: Preparation and Characterization Using Spectrophotometry, EPR and H MAS NMR.

Hydroxyapatite is the main constituent of mammalian hard tissues. Basic applications of synthetic hydroxyapatites include bone and dental implantology and drug delivery systems. The study of hydroxyapatite surface properties could give greater insight into the processes of bone mineralization and degradation.

The solid-state proton NMR study of bone using a dipolar filter: apatite hydroxyl content animal age.

The hydroxyl content of bone apatite mineral has been measured using proton solid-state NMR performed with a multiple-pulse dipolar filter under slow magic angle spinning (MAS). This new method succeeded in resolving and relatively enhancing the main hydroxyl peak at 0 ppm from whole bone, making it amenable to rigorous quantitative analysis. The proposed methodology, involving line fitting, the measurement of the apatite concentration in the studied material and adequate calibration, was proved to be convenient and suitable for monitoring bone mineral hydroxylation in different species and over the lifetime of the animal.

Synthesis and characterization of MCM-48/hydroxyapatite composites for drug delivery: Ibuprofen incorporation, location and release studies.

MCM-48 is crystalline, mesoporous silicate used in catalysis and for adsorption various molecules to create useful materials for chemistry, pharmacy and medicine. In this work, the MCM-48 silicate has been coated with nanohydroxyapatite (HA) to design a new drug delivery system. The MCM-48/hydroxyapatite composite was synthesized using a new method involving precipitation of HA onto the earlier prepared MCM-48.

Pharmaceutical cocrystals, salts and polymorphs: Advanced characterization techniques.

The main goal of a novel drug development is to obtain it with optimal physiochemical, pharmaceutical and biological properties. Pharmaceutical companies and scientists modify active pharmaceutical ingredients (APIs), which often are cocrystals, salts or carefully selected polymorphs, to improve the properties of a parent drug. To find the best form of a drug, various advanced characterization methods should be used.

Convenient UV-spectrophotometric determination of citrates in aqueous solutions with applications in the pharmaceutical analysis of oral electrolyte formulations.

Herein, we present a convenient method for quantitative spectrophotometric determination of citrate ions in aqueous solutions in the middle-UV range. It involves measuring the absorbance of citric acid at 209 nm under suppressed dissociation at pH < 1.0 in the presence of hydrochloric acid.

Pharmaceutical properties of two ethenzamide-gentisic acid cocrystal polymorphs: Drug release profiles, spectroscopic studies and theoretical calculations.

The aim of this study was to evaluate the stability and solubility of the polymorphic forms of the ethenzamide (ET) - gentisic acid (GA) cocrystals during standard technological processes leading to tablet formation, such as compression and excipient addition. In this work two polymorphic forms of pharmaceutical cocrystals (ETGA) were characterized by C and N solid-state nuclear magnetic resonance and Fourier transformed infrared spectroscopy. Spectroscopic studies were supported by gauge including projector augmented wave (GIPAW) calculations of chemical shielding constants.

Prazosin-Conjugated Matrices Based on Biodegradable Polymers and α-Amino Acids--Synthesis, Characterization, and in Vitro Release Study.

Novel and promising macromolecular conjugates of the α1-adrenergic blocker prazosin were directly synthesized by covalent incorporation of the drug to matrices composed of biodegradable polymers and α-amino acids for the development of a polymeric implantable drug delivery carrier. The cyto- and genotoxicity of the synthesized matrices were evaluated using a bacterial luminescence test, protozoan assay, and Salmonella typhimurium TA1535. A new urethane bond was formed between the hydroxyl end-groups of the synthesized polymer matrices and an amine group of prazosin, using 1,1'-carbonyldiimidazole (CDI) as a coupling agent.

Near-Infrared (NIR) Spectroscopy of Synthetic Hydroxyapatites and Human Dental Tissues.

Near-infrared spectroscopy (NIR) was used to analyze synthetic hydroxyapatite calcined at various temperatures, synthetic carbonated hydroxyapatite, and human hard dental tissues (enamel and dentin). The NIR bands of those materials in the combination, first-overtone, and second-overtone spectral regions were assigned and evaluated for structural characterization. They were attributed to adsorbed and structural water, structural hydroxyl (OH) groups and surface P-OH groups.

Crystal structures of tiotropium bromide and its monohydrate in view of combined solid-state nuclear magnetic resonance and gauge-including projector-augmented wave studies.

Tiotropium bromide is an anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease. The crystal structures of this compound and its monohydrate have been previously solved and published. However, in this paper, we showed that those structures contain some major errors.

Solid-state NMR as an effective method of polymorphic analysis: solid dosage forms of clopidogrel hydrogensulfate.

Clopidogrel hydrogensulfate (HSCL) is an antiplatelet agent, one of top-selling drugs in the world. In this paper, we have described a rapid and convenient method of verification which polymorph of HSCL is present in its final solid dosage form. Our methodology based on solid-state NMR spectroscopy and ab initio gauge-including projector-augmented wave calculations of NMR shielding constants is appropriate for currently available commercial solid dosage forms of HSCL.

Solid-state NMR studies of theophylline co-crystals with dicarboxylic acids.

In this work, three polycrystalline materials containing co-crystals of theophylline with malonic, maleic, and glutaric acids were studied using (13)C, (15)N and (1)H solid-state NMR and FT-IR spectroscopy. The NMR assignments were supported by gauge including projector augmented waves (GIPAW) calculations of chemical shielding, performed using X-ray determined geometry. The experimental (13)C cross polarization/magic angle spinning (CP/MAS) NMR results and the calculated isotropic chemical shifts were in excellent agreement.

Ampicillin-ester bonded branched polymers: characterization, cyto-, genotoxicity and controlled drug-release behaviour.

The development and characterization of novel macromolecular conjugates of ampicillin using branched biodegradable polymers has been described in this study. The conjugates have been prepared coupling the β-lactam antibiotic with branched polymer matrices based on the natural oligopeptide core. The cyto- and genotoxicity of the synthesized polymers were evaluated with a bacterial luminescence test, two protozoan assays and Salmonella typhimurium TA1535.

Comparative proton nuclear magnetic resonance studies of amantadine complexes formed in aqueous solutions with three major cyclodextrins.

Host-guest complexes of alpha-, beta-, and gamma-cyclodextrins (α-CD, β-CD, and γ-CD, respectively) with amantadine (1-aminoadamantane, AMA; an antiviral agent) were characterized in aqueous solutions using proton nuclear magnetic resonance (NMR) spectroscopy. Host-guest molecular interactions were manifested by changes in the chemical shifts of AMA protons. NMR Job's plots showed that the stoichiometry of all the studied complexes was 1:1.

Solid-state MAS NMR, TEM, and TGA studies of structural hydroxyl groups and water in nanocrystalline apatites prepared by dry milling.

A series of nanocrystalline calcium hydroxyapatites was prepared by dry milling and characterized using proton and P MAS NMR, TEM, and TGA methods. The samples contained stubby rod-shaped crystals, which length and width varied in the 130-30 and 95-20 nm ranges, respectively. It was confirmed that concentration of structural hydroxyl groups in nanocrystalline apatites decreases with the decreasing crystal size.

Solid-state NMR and IR characterization of commercial xenogeneic biomaterials used as bone substitutes.

Three commercial xenogeneic biomaterials (Gen-Os, Apatos Spongiosa and Apatos Cortical; all from Tecnoss Dental, Torino, Italy) originated from porcine bone were characterized by various analytical methods, such as powder X-ray diffraction (XRD), thermogravimetry (TGA), high-resolution solid-state nuclear magnetic resonance (ssNMR) and infrared spectroscopy (FT-IR). The studies were focused on structural properties and chemical compositions of the samples. It was found that the main constituents of the analyzed biomaterials were nanocrystalline apatite mineral, organic collagenous matrix and water.

Synthesis and properties of a star-shaped poly(ϵ-caprolactone)-ibuprofen conjugate.

A series of novel star-shaped poly(ϵ-caprolactone) (PCL) biodegradable polyesters were synthesized through ring-opening polymerization of ϵ-caprolactone in the presence of a poly(amidoamine) (PAMAM) dendrimer initiator. The polymers (PAMAM/PCLs) were obtained with a high yield (92%) and a number-average molecular weight of up to 14 000 g/mol. The nonlinear structure of PAMAM/PCLs was confirmed by nuclear magnetic resonance, gel-permeation chromatography, thermogravimetric analysis and differential scanning calorimetry.

Preparation and characterization of polyester- and poly(ester-carbonate)-paclitaxel conjugates.

The polyester- and poly(ester-carbonate)-paclitaxel conjugates with low molecular weight were synthesized using dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP) as catalysts. Polymeric matrices were obtained by ring-opening polymerization of ɛ-caprolactone (CL), rac-lactide (rac-LA), l-lactide (LLA) and trimethylene carbonate (TMC). The macromolecular conjugates were characterized by using spectroscopic techniques, such as (1)H, (13)C NMR and FTIR.

Use of aliphatic poly(amide urethane)s for the controlled release of 5-fluorouracil.

The controlled release of 5-fluorouracil (5FU) from aliphatic poly(amide urethane)s (PURs) was studied in vitro. Linear PUR conjugates were prepared by the reaction between oligo(ɛ-caprolactone) (PCL), oligolactide (PLA), copolymers of ɛ-caprolactone (CL) and rac-lactide (rac-LA), dihydroxy(polyethylene adipate) (OEDA) with 1,6-diisocyanatohexane (HDI). Release of 5FU from PURs was found to depend on the nature of oligoester units and consist of soft and hard segments.

Kinetics of 1H→13C NMR cross-polarization in polymorphs and solvates of the antipsychotic drug olanzapine.

The (1)H→(13)C NMR cross-polarization (CP) was studied under magic-angle spinning at 7.5 kHz in various crystal forms of the antipsychotic drug olanzapine: two polymorphs (metastable I and stable II) and eight solvates containing organic solvent and water molecules. The CP kinetics followed the non-classical I-I(*)-S model, in which CP begins in a spin cluster of proximate abundant spins I(*) and rare spins S, then is controlled by spin diffusion of the abundant spins I from bulk to the I(*) spins of the spin cluster and finally is governed by spin-lattice relaxation of the abundant spins in the rotating frame.

Synthesis and study of controlled release of ofloxacin from polyester conjugates.

New polymeric conjugates were prepared coupling ofloxacin to two-, three-, four and six-arm, star-shaped poly(ɛ-caprolactone) and polylactide. The homopolymers were synthesized via ring-opening polymerization of ɛ-caprolactone, l-lactide and rac-lactide in the presence of glycerol, penthaerythritol, dipentaerythritol and poly(ethylene glycol) as initiators and stannous octoate as a catalyst. The conjugates were characterized by GPC, MALDI-TOF MS, NMR, IR and viscosity methods.

X-ray diffraction, FT-IR, and (13)C CP/MAS NMR structural studies of solvated and desolvated C-methylcalix[4]resorcinarene.

Solid C-methylcalix[4]resorcinarene solvated by acetonitrile and water (CAL-Me) and then modified by slow solvent evaporation (CAL-Me*) was studied using single-crystal and powder X-ray diffraction, FT-IR, and (13)C CP/MAS NMR. The CAL-Me solvate crystallizes in the monoclinic P2(1)/n space group with three CH(3)CN and two H(2)O molecules in the asymmetric part of the unit cell. The CAL-Me molecules adopt a typical crown conformation with all of the hydroxyl groups of the aryl rings oriented up and all of the methyl groups disposed down (the rccc isomeric form).

Seeking polymeric prodrugs of norfloxacin. Part 2. Synthesis and structural analysis of polyurethane conjugates.

Oligo(epsilon-caprolactone) and oligolactide were synthesized via ring-opening polymerization of cyclic esters in the presence of creatinine as initiators. Thus obtained oligomers were successfully used in the synthesis of novel polyurethane conjugates of norfloxacin. The structures of the polymers and conjugates were elucidated by means of MALDI-TOF MS, NMR and IR studies.

Kinetics of solid-state NMR cross-polarization from protons to carbon-13 in surgical sutures.

Commercial Dexon surgical sutures, made of polyglycolide (PGA), were examined using (13)C CP/MAS NMR. The study shows that detailed analysis of the cross-polarization (CP) process is useful in the peak assignments and in the assessment of molecular mobility in the polymer domains. Crystallinity of PGA in the sutures was estimated at ca.

Polymerization of cyclic esters initiated by carnitine and tin (II) octoate.

Low-molecular weight poly(epsilon-caprolactone), polylactides and copolymers of epsilon-caprolactone and lactides were obtained by the polymerization of cyclic esters in the presence of a carnitine/SnOct(2) system. Their structures were proven by means of MALDI-TOF, IR and NMR studies. Effects of temperature, reaction time and carnitine dosage on the polymerization process were examined.

Kinetics of 1H --> 31P NMR cross-polarization in bone apatite and its mineral standards.

Kinetics of NMR cross-polarization (CP) from protons to phosphorus-31 nuclei was studied in the following samples: mineral of whole human bone, apatite prepared from bone, natural brushite, synthetic hydroxyapatite (hydrated and calcined), and synthetic carbonatoapatite of type B with 9 wt% of CO(3) (2-). In order to avoid an effect of magic angle spinning on CP and relaxation, the experiments were carried out on static samples. Parameters of the CP kinetics were discussed for trabecular and cortical bone tissue from adult subjects in comparison to the synthetic mineral standards.