Biomedical subjects

A P Simonelli

Publications and source records attributed to A P Simonelli.

At least 19 recordsLinked to original sources

PubMed1992

Alkaline hydrolysis of oligomers of tartrate esters: effect of a neighboring carboxyl on the reactivity of ester groups.

The importance and the effect of neighboring groups on the hydrolysis of polymeric esters were demonstrated. Several oligomers of poly(butylene tartrate) were synthesized, and their kinetic behavior was studied under alkaline conditions. The oligomers and their degradation products were monitored by HPLC and identified by fast atom bombardment mass spectrometry. The rates of hydrolysis measured at pH 5-8 and at 75 degrees C indicate that the degradation of the oligomers obeyed pseudo-first-order kinetics. The rate of hydrolysis among the homologous series of oligomers increased as the molecular weight increased. However, the increase in hydrolysis rate was not proportional to the number of ester linkages in the oligomers. This deviation was explained on the basis of electrostatic repulsion of the neighboring carboxylate group toward the hydroxide ion. The calculations revealed that the electrostatic effect was so great that the ester linkage adjacent to the carboxylate anion did not contribute to the overall rate of hydrolysis. The technique presented here can be extended to any multifunctional-group compound that has repeat units and can undergo a specific reaction that can be accurately measured.

Algorithms↗

PubMed1991

Determination of specific rate constants of specific oligomers during polyester hydrolysis.

Aliphatic polyesters have great utility as temporary prosthetics and surgical aids, and in drug delivery systems. Knowledge of the mechanism and pathways of hydrolysis can form a basis for the design and selection of a controlled-release system. Because of the importance of hydrolysis to the properties of such a system, a technique was developed to accurately determine the specific rate constants and relevant kinetic parameters for the specific oligomers from the reaction mixture of polyesters undergoing hydrolysis. A detailed kinetic analysis of the acid hydrolysis of well-characterized oligomers of polyesters is presented. Several oligomers of poly(butylene tartrate)s were synthesized and their kinetic behavior was studied under acidic conditions. The oligomers and their degradation products were monitored by HPLC and identified by fast-atom bombardment mass spectrometry. From the rates of hydrolysis measured from pH 1 to 3.0 and at temperature of 75 degrees C, it becomes evident that the degradation of the oligomers obeys pseudo-first-order kinetics. The rate of hydrolysis among the homologous series of oligomers increases as the molecular weight increases. The hydrolysis was catalyzed by hydrogen ion; the catalytic rate constant increased predictably with the number of ester linkages present in the molecule. The reaction is first order with respect to the catalyst concentration and the number of ester linkages. Good agreement was obtained with a model in which the individual rate of bond cleavage depends only on the statistical factor. The technique described in this paper is unique for the determination of polyester hydrolysis pathways and isolation of any structural effects on the rates of hydrolysis.

Chemical Phenomena↗

PubMed1990

Pseudo-first-order alkaline hydrolysis of diethyl tartrate: a baseline study for a polymer matrix used in controlled-release delivery systems.

The hydrolysis kinetics of a bifunctional group compound, diethyl tartrate, was studied as a function of temperature and pH in the alkaline region. A pH-stat was used to maintain constant pH conditions in the alkaline region. This allowed the studies to be carried out at low ionic strengths and without the use of buffers. The results indicate that the hydrolysis for both steps followed specific base catalysis. The ratio of the two rate constants was 13.31, which was attributed to a strong charge effect in the second step. The results also show that the use of an overall average rate constant may not be acceptable for multifunctional group compounds.

Carboxylic Acids↗

PubMed1989

Analysis of consecutive pseudo-first-order reactions. II: Calculation of the rate constants from the co-product or co-reactant data.

The co-product or co-reactant data for a two-step pseudo-first-order consecutive reaction gives unique shape profiles for the natural logarithm of the concentration versus time plots, based on the ratio of two rate constants (k2/k1), for theoretical data without error. But, in the presence of a +/- 2.0% random error in the simulated data, the ability to distinguish between different shapes disappears. A comprehensive analysis shows that accurate rate constants can be obtained only in a limited range of k2/k1 ratios. Reliable rate constants can be obtained when k2/k1 less than 0.5. Two special cases, k1 approximately 2k2 and k2 much greater than k1, cannot be distinguished from each other and could lead to erroneous conclusions if additional information is not used to identify the correct ratio. When k2/k1 greater than 0.5, the calculated parameters are extremely sensitive to experimental errors, and other techniques involving the concentrations of starting material and intermediate should be used to obtain the rate constants.

Chemistry, Pharmaceutical↗

PubMed1989

Use of liquid chromatography and mass spectroscopy to select an oligomer representative of polyester hydrolysis pathways.

An analytical method has been developed for the simultaneous determination of a series of low molecular weight biodegradable polyesters and its degradation products. The separation is accomplished using a strong anion exchange HPLC column. The polyester and its degradation products are identified by fast atom bombardment mass spectrometry. This technique will enable one to establish the polyester hydrolysis pathways and determine accurate kinetic parameters.

Chromatography, High Pressure Liquid↗

PubMed1988

Analysis of consecutive pseudo-first-order reactions. I: An evaluation of available methods to calculate the rate constants from co-product or co-reactant data.

Co-product or co-reactant data is commonly used to obtain the hydrolysis rate constants for two-step consecutive pseudo-first-order reactions. Different methods to calculate the rate constants from experimental data were evaluated using data simulated with and without a +/- 2% random error. The results of this analysis indicate that the ability to determine the value and accuracy of the rate constants obtained by the different methods depends on the k2/k1 ratio. In certain ranges of k2/k1 ratios, erroneous results are obtained which have occasionally led to incorrect conclusions by authors in the literature.

Chemical Phenomena↗

PubMed1985

Relationship between powder surface characteristics and viscoelastic properties of powder-filled semisolids.

The viscoelastic properties of dispersions of powdered zinc oxide in anhydrous lanolin and colloidal sulfur in anhydrous lanolin were characterized by dynamic mechanical testing. The elastic shear modulus, G', viscous shear modulus, G", and loss tangent (damping), tan delta, were determined as a function of shear frequency, v, temperature, T, and volume fraction of powder, phi 2. A priori, it might be expected that zinc oxide and colloidal sulfur would elicit different viscoelastic properties due to their contrasting surface characteristics; zinc oxide has a hydrophilic surface and colloidal sulfur has a hydrophobic surface. Even though constitutive mathematical models, derived to predict the mechanical behavior of solid-filled polymeric materials, were not designed to account for differences in surface characteristics of the filler, the findings of these experiments show that these models are useful in explaining the differences in viscoelastic behavior of powder-filled semisolids due to surface characteristics of the filler. One model of particular value was the Kerner equation. With it, mechanisms were postulated for zinc oxide-zinc oxide interactions, sulfur-sulfur interactions, zinc oxide-anhydrous lanolin interactions, and sulfur-anhydrous lanolin interactions, within dispersions as a function of nu, T, and phi 2. In addition, damping was used to further identify the influence of temperature. Data obtained from three temperatures, where anhydrous lanolin exists in three different structural states, shows that the influence of the powder on damping is not only determined by the surface characteristics of the powder but also the structural state of anhydrous lanolin.

Chemical Phenomena↗

PubMed1984

Application of dynamic mechanical testing to characterize the viscoelastic properties of powder-filled semisolids.

A nondestructive technique, dynamic mechanical testing, was used to characterize the viscoelastic properties of dispersions of powdered starch in anhydrous lanolin. The elastic shear modulus (G'), viscous shear modulus (G"), and loss tangent (damping; tan delta) were determined as a function of shear frequency, temperature, and the volume fraction of starch. The results of these studies show that constitutive mathematical models, derived to predict the mechanical behavior of solid-filled polymeric materials, can be applied to solid-filled semisolid pharmaceuticals. In particular, the Kerner equation was useful in describing the influence of starch on the G' of the dispersions. Even though the Kerner equation was unable to predict viscoelastic behavior at all shear frequencies, temperatures, and starch volume fractions, it proved beneficial in postulating mechanisms for starch-starch and starch-anhydrous lanolin interactions within the dispersions. In addition, damping was able to differentiate the influence of temperature. Data obtained from three temperature ranges, where anhydrous lanolin exists in three different structural states, shows that the influence of starch on damping is dictated by the structural state of anhydrous lanolin.

Chemical Phenomena↗

PubMed1983

Phenomenological viscoelasticity of a heterogeneous pharmaceutical semisolid.

This study presents the results of an investigation of the viscoelastic properties of anhydrous lanolin USP, as determined by dynamic mechanical testing. The elastic shear modulus (G'), viscous shear modulus (G"), and loss tangent (tan delta) were determined as a function of shear frequency, nu, (0.01--10.0 Hz) and temperature, T, (0--30 degrees). These viscoelastic parameters were found to be temperature and shear frequency dependent. Up to 100-fold changes in shear moduli and tan delta values were observed with appropriate changes in T and nu. Many of the observed properties are also characteristic of high molecular weight polymers and can be attributed to a high degree of molecular structure. It was found that dynamic mechanical testing was a sensitive tool for measuring structural changes, and was especially useful in detecting a major structural transition well below the accepted melting temperature of anhydrous lanolin.

Elasticity↗

PubMed1983

Temperature-frequency equivalence of the viscoelastic properties of anhydrous lanolin USP.

Methods of data analysis novel to pharmaceutical semisolids have been applied to the dynamic mechanical data obtained for anhydrous lanolin USP. It was found that the viscoelastic parameters determined over a wide range of temperatures and shear frequencies could be superposed. Elastic moduli (G') and viscous moduli (G") obtained at low temperatures (T) and frequencies (nu), were equivalent to moduli obtained at high T and nu. Empirical shifts of modulus versus shear frequency data obtained at different temperatures were used to produce G' and G" versus nu master curves (complete log modulus versus log frequency behavior at a constant temperature). A method of reduced variables, in conjunction with an Arrhenius-type relation, proved useful in calculating the energy of activation for the structural processes involved in a major mechanical transition.

Elasticity↗

PubMed1976

Dissolution rates of high energy sulfathiazole--povidone coprecipitates II: characterization of form of drug controlling its dissolution rate via solubility studies.

Solubility studies were made to characterize the form of sulfathiazole controlling the rate of dissolution exhibited in previously reported dissolution rate studies of sulfathiazole coprecipitated with povidone. The aqueous solubility of the high energy form of sulfathiazole obtained using sulfathiazole--povidone coprecipitates was determined in the presence of polymer in solution. Its aqueous solubility in the absence of polymer was determined by extrapolation. The solubility value was much greater than either the supercooled melt or the crystalline forms of sulfathiazole. Stabilization of these sulfathiazole solutions supersaturated with respect to the more stable crystalline form was achieved by the addition of sufficient polymer to the solution to prevent nucleation of the crystalline form. The concentration of polymer required to prevent nucleation of the crystalline forms was much higher than the previously reported concentrations required to inhibit crystal growth of sulfathiazole. The ratio of the solubility value obtained for the coprecipitated sulfathiazole as compared with its crystalline form I was in agreement with the ratio of their dissolution rates obtained the plateau regions of the dissolution rate experiments reported previously. The extrapolated aqueous solubility values in the absence of povidone were obtained as a function of temperature and were utilized to obtain thermodynamic parameters. The difference in the heat of solution of the two forms of sulfathiazole from the slope of the van't Hoff plots of the extrapolated solubility values was 1618 cal/mole, in excellent agreement with the literature value. The free energy, enthalpy, and entropy at 27 degrees for the coprecipitated drug relative to its crystalline form I were 1125 cal/mole, 8439 cal/mole, and 24 eu, respectively, indicating the high degree of molecular randomness and lack of structure in these high energy systems. These results provide strong evidence for the presence of an amorphous state of sulfathiazole as the controlling phase of both the solubility and dissolution rate experiments involving the high energy form of sulfathiazole obtained by coprecipitation with povidone.

Crystallization↗

PubMed1974