J. M. Barrales-Rienda

Release of gentamicin sulphate from a modified commercial bone cement. Effect of (2-hydroxyethyl methacrylate) comonomer and poly(N-vinyl-2-pyrrolidone) additive on release mechanism and kinetics

The influence of the (2-hydroxyethyl methacrylate) (HEMA) monomer addition as a comonomer to the cement liquid component and of a polymer, poly(N-vinyl-2-pyrrolidone) (PVP) to the solid component of a standard CMW-1 bone cement on gentamicin sulphate (GS) on its drug release properties have been studied. The addition of HEMA modifies the habit of the delivery curves. The incorporation of PVP into the cement matrix, apparently, did not very much modify the shape of the HEMA modified cement release curves, but led to a remarkable increase of the maximum amount of GS released. This effect was proportional to the PVP concentration incorporated. From the matrix composition and SEM data, a model based on the morphology of the matrix has been proposed. The cumulative amount of GS released by each slab Mt is most adequately fitted and represented by the equation Mt = c + at 1/2 + b[1 - exp(-nt)], which corroborates that the release occurs according to the model proposed. by means of three discrete mechanisms, namely: (i) a short-term initial elution due to the imperfections in the poly(methyl methacrylate) covering of the most external GS beads, burst effect by the buffer solution; (ii) followed by a fracture by stress cracking in an active media of the coated GS beads located on the external surface of the matrix where water molecules enter to dissolve GS molecules releasing them into the buffer solution by a diffusion-controlled process; and (iii) a third process in which the buffer solution penetrates into the internal voids and cracks creating a series of channels in a labyrinthic structure, which may facilitate the access of water molecules to the plastic-coated GS beads within the bulk matrix. This third process is enhanced by the incorporation of PVP beads as dissolved molecules within the matrix. This water-soluble additive is leachable, generating a highly porous structure in the cement. This HEMA and PVP modified cement may be used as a drug delivery system to modulate the GS release rate.

Sequence distribution and stereoregularity in methyl methacrylate-methyl acrylate copolymers at high conversions

Abstract Methyl methacrylate (MMA)-methyl acrylate (MA) copolymerizations have been analysed over a wide range of conversions with the purpose of predicting the changes in copolymer composition and comonomer sequence distribution as a function of conversion. High resolution 1 H n.m.r. spectra (200 MHz) of MMA-MA copolymers, prepared at two overall comonomer concentrations by free radical copolymerization in benzene solution at 50°C at low conversion, have been analysed in terms of comonomer composition, sequence distribution and stereoregularity. Reactivity ratios for the terminal model, statistical parameters, P ij , and co-isotacticity parameters, σ 11 = 0.23 and σ = σ 12 = σ 21 = 0.50, estimated at low conversion were used to describe the changes in copolymer composition and triad fraction intensities with conversion. The experimental sequence distribution intensities were in agreement with the estimated values. From the good agreement found between experimental and calculated values, it can be concluded that the terminal model, through reactivity ratios and Bernoullian statistics, provides a very precise description of copolymerization over the whole range of conversion and composition and overall concentration of monomers.

The influence of the copolymer composition on the diltiazem hydrochloride release from a series of pH-sensitive poly[(N-isopropylacrylamide)-co-(methacrylic acid)] hydrogels.

A series of poly[(N-isopropylacrylamide)-co-(methacrylic acid)] (P[(N-iPAAm)-co-(MAA)]) hydrogels was investigated to determine the composition that exhibits a better pH-modulated release of diltiazem hydrochloride (DIL.HCl). For this purpose hydrogel slabs were loaded with DIL.HCl by the immersion method, and its release under acidic medium (0.1N HCl, pH 1.2) and in phosphate buffer pH 7.2, using United States Pharmacopeia (USP) 24 Apparatus 1, was investigated. According to the results from the slabs, copolymers with 85% mol N-iPAAm content were selected to prepare tablets with different particle size. The effect of pH and particle size changes on DIL.HCl release from these last hydrogel tablets was investigated by a stepwise pH variation of the dissolution medium. The amount of DIL.HCl released from high N-iPAAm content copolymer slabs under acidic pH medium was not only very low but it was also released at a slow rate. In the 85% N-iPAAm tablets, significant differences between and within release profiles were found as a function of particle size and pH, respectively. A relationship between particle size and release rate has been found. The lower DIL.HCl release at acidic pH from enriched N-iPAAm copolymers is interpreted by a cooperative thermal- and pH-collapse. Although for the whole range of copolymer composition a dependence of the equilibrium of swelling on the pH was found, DIL.HCl release experiments indicated that hydrogels with 85% mol N-iPAAm are the more adequate to be used for modulated drug delivery systems. Additionally, the particle size of the tablet can be used to tailor the release rate.

Synthesis of N-(fluoro phenyl) maleamic acids and N-(fluoro phenyl) maleimides

Abstract A series of seven N-(fluoro phenyl) maleamic acids and their N-(fluoro phenyl) maleimides were prepared by the reaction of fluoro phenyl amines ( o-, m-, and p-fluoro, 2.4-, 2.5-difluoro, 2.3.5.6-tetrafluoro and 2.3.4.5.6.-pentafluoro anilines) with maleic anhydride according to substantial modifications made to the reaction conditions used by Searle for the preparation of normal N-aryl maleimides.

Polymer precursors of polyacetylene. Thermal degradation of poly(vinyl esters). Part 1-Molecular weight dependence of the autocatalytic thermal degradation of poly(vinyl acetate) (PVAc)

This study is the first of a series on the pyrolyses of poly(vinyl esters) in which the kinetics of the isothermal degradation up to high conversions of five unfractionated heterotactic samples of poly(vinyl acetate) (PVAc) ranging in viscosity-average molecular weight Mv from 3·7 × 104 to 2·4 × 105 has been investigated by a static procedure in a nitrogen atmosphere over a wide temperature range. The experimental results can be explained by assuming the occurrence of a catalyzed deacetylation reaction which is first order with respect to CH3COOH simultaneously with an uncatalyzed reaction. This kinetic model, based on the stripping mechanism, has been shown to be in very good agreement with the experimental data not only for low, but also for moderately high, degrees of conversion. Rate constants k1 and k2, Arrhenius parameters E and A and ΔS≠ values have been determined for both the autocatalyzed and uncatalyzed elimination reactions. They are reasonable, since they compare quite favorably with those taking place by a unimolecular dissociation mechanism in homogeneous gas-phase reactions of simple ester molecules which we can consider as model substances for our stripping elimination reaction. The dependence of the kinetic parameters of the samples on molecular weight has been interpreted.

Dynamic mechanical and dielectric behavior of erucamide (13-cis-docosenamide), isotactic poly(propylene), and their blends

Blends of erucamide (13-cis-docosenamide) and isotactic poly(propylene) were analyzed by means of dynamic mechanical (at 3, 10, and 30 Hz) and dielectric (at 1, 6, and 20 kHz) techniques. The dependence of tan δ with temperature for each one of the blends has been fitted to Gaussian functions in order to deconvolute the overlapped relaxations. Three relaxations for i-PP, αi-PP, βi-PP, γi-PP, three for erucamide, αERU, βERU, and γERU, and five for their blends have been observed and assigned. They do not vary appreciably with composition, suggesting that the components are incompatible either as globules in the matrix or in the amorphous regions of the spherulites, and/or in their surroundings.

Solubility of erucamide (13-cis docosenamide) in isotactic poly(propylene) and thermal behaviour of their blends

Abstract Differential scanning calorimetry studies, made on blends prepared by mixing in the melt, have demonstrated that crystallization of erucamide (13- cis -docosenamide) [H 3 C-(-CH 2 -) 7 -HC=CH-(-CH 2 -) 11 -CO-NH 2 ]/ isotactic poly(propylene (i-PP) blends results in separate crystals of the two components, rather than cocrystallization. For low content erucamide blends (less than 29%), two melting peaks for erucamide have been observed. They have been assigned to: i) erucamide crystals situated in the external surfaces of the i-PP and located forming globules, droplets or inclusions whose melting point appears at the higher temperature (Erucamide I); ii) erucamide crystals forming crystalline microdomains of erucamide, located either within the amorphous region of spherulites and/or in the amorphous regions which surround the spherulites (Erucamide II). The enthalpy of these crystals located in these regions, i.e. in the amorphous region of the spherulites and/or their surroundings, has been estimated. A good linear correlation has been found between the solubility of erucamide crystals in the amorphous region of i-PP spherulites and/or the surrounding region of the spherulites and their apparent melting enthalpy. Spherulite radial growth rates, G , for the different blends are lower than for the pure i-PP. They show a characteristic dependence on the erucamide content in the blend. This behaviour is in agreement with theoretical predictions for crystallization in immiscible blends. An additional feature, as an unambiguous test of the incompatibility, is the poor interfacial adhesion, which has been made clear from the large voids left on the fracture surface where the erucamide globules have separated from the matrix and from the smooth surfaces of the exposed erucamide globules. A model is proposed for erucamide/i-PP blends, which is able to explain quantitatively in detail all the thermal and morphological experimental data.

On the radiation-induced solid state polymerization of N-phenyl maleimide

Abstract The solid-state polymerization of N -phenyl maleimide (NPMI) induced by 60 Co γ-rays was studied above and below its melting point over the range 70–93. The conversion increases on raising the irradiation temperature. The polymers were characterized by elemental analysis, intrinsic viscosity, spectroscopy (u.v., i.r. NMR), programmed thermogravimetric analysis and X-ray diffraction. Infra-red spectra of polymers prepared by radiation were nearly identical with those of polymers obtained by free radical polymerization in bulk or in solution. The X-ray diffractograms of all samples show two rather broad peaks indicative of non-crystalline structures. The locations of the peaks do not depend upon the irradiation temperature. The average “cluster size”, calculated from the broadening of the innermost maximum, is strongly dependent on the irradiation temperature: hence it is indicative of the presence of well defined short range order. It has been suggested that some of the i.r. absorption bands in poly N -phenyl maleimides disappearing in solution may be assigned to “regularity”. The existence of such bands confirms the short range order proposed for packing in the solid state but also associated with long stereoregular chain sequences of the threo di-syndiotactic type.

Fickian diffusion of erucamide (13-cis-docosenamide) in poly(laurolactam) (Nylon 12) (PA-12)

Diffusion of erucamide (13-cis-docosenamide) [H3C— (—CH2—)11—HC=CH—(—CH2—)7—CO— NH2] (eru) in poly(laurolactam) (Nylon 12) (PA-12) has been studied in a temperature range from 343 to 353 K. In previous investigations on the diffusion of eru in isotactic poly(propylene) (i-PP) it was found that the diffusion took place by a non-Fickian mechanism. This feature was explained by taking into account the microstructure of i-PP films and the incompatibility of eru and i-PP. The same experimental method to determine the concentration profiles was previously employed in this system. The experimental profiles have been compared with theoretical curves based on solutions of Ficks diffusion equation for the best fitting, with the appropriate boundary conditions. The measured concentration profiles show a good agreement with the Fickian law. Values of the diffusion coefficient D in the range from 10–10 to 10–11 cm2·s–1 have been obtained. The activation energy for diffusion (Ed) has been calculated from the D values in the temperature range investigated assuming an Arrhenius-type behaviour. The activation energy has been calculated as Ed = 156 kJ·mol–1. The values of diffusion coefficients and activation energy are in the range found for some other additives. By using Fujitas equation a good correlation between diffusion coefficient and free volume fraction estimated by means of the Williams-Landel-Ferry equation have been found.

Polymer precursors of polyacetylene. Thermal degradation of poly(vinyl esters). Part II—Effect of the n-acyl chain length on the autocatalytic thermal degradation of a homologous series of poly(vinyl n-alkyl esters) (PV-n-AEs)

Abstract In order to determine the effect of the length of the n -acyl portion on the autocatalytic thermal elimination reaction, five of the shorter members of the homologous series of poly(vinyl n -alkyl esters) (PV- n -AEs) were studied under identical experimental conditions; namely, by a static procedure at several temperatures. The -R group was varied from one to five carbon atoms. All the PV- n -AEs were obtained by chemical modification of a unique sample of poly(vinyl alcohol) (PVA). Thus, by using a homologous series of PV- n -AEs with the same backbone molecular weight, any possible effect due to a change in molecular weight of the backbone and/or tacticity, structural chemical irregularities, etc., is eliminated. The shortest member of the series, i.e. poly(vinyl acetate) (PVAc) clearly degrades by an autocatalytic mechanism more readily than do longer ones. Thus, PVAc exhibits pure autocatalytic thermal degradation kinetics. On the contrary, the longest member of the series, poly(vinyl n -hexanoate ester) (PV- n -HE), degrades by very well defined first order kinetics. The other members of the series, poly(vinyl propionate) (PVPr), poly(vinyl butyrate) (PVBu) ≡ poly(vinyl n -butanoate ester) (PV- n -BE) and poly(vinyl valerate (PVVa) ≡ poly(vinyl n -pentanoate ester) (PV- n -PE) degrade by first order kinetics but with the participation, although to an insignificant extent, of the autocatalytic mechanism. For this and certain other reasons we have analyzed our experimental results by taking into account both types of mechanisms, separately. The three latter compounds followed first order rate kinetics quite well, the rate constants depending upon the n -alkyl chain length of the acyl portion. The energy of activation of the first order reaction decreases markedly as the length of the n -acyl portion increases. This decrease is neither constant nor regular as the acyl moeity increases in length but rather takes place in a quasi zig-zag fashion particularly with the longer members, suggesting an odd-even effect. On the basis of our experimental results we have arrived at the two following conclusions. Firstly, less stable poly(vinyl n -alkyl esters), i.e. poly(vinyl n -hexanoate ester) and, of course, higher members of the series which have not been investigated in the present work, would allow lower pyrolysis temperatures, thus increasing the synthetic applicability of this stripping reaction to the preparation of polyacetylene-like structures. Secondly, it was hoped that the kinetic study itself would shed more light on the mechanism of these decompositions in high molecular weight compounds.