Compatibility study of tobramycin and pharmaceutical excipients using differential scanning calorimetry,FTIR, DRX,and HPLC

Differential scanning calorimetry (DSC), isothermal stress testing–Fourier transform infrared spectroscopy (IST–FTIR), isothermal stress testing–high-performance liquid chromatography, and powder X-ray diffraction (PDRX) were used as screening techniques for assessing the compatibility of tobramycin with some currently employed ophthalmic excipients. In the first phase of the study, DSC was used as a tool to detect any interaction. The absolute value of the difference between the enthalpy of the pure tobramycin melting peak and that of its melting peak in the different analyzed mixtures was chosen as a parameter of the drug–excipient interaction degree. DSC results demonstrated that benzalkonium chloride, monobasic sodium phosphate, boric acid, edetate disodium, sodium metabisulfite, thimerosal, and potassium sorbate interact with tobramycin. Taking into account these results, it could be suggested that some of the changes observed in the IST–FTIR spectra of binary blends of tobramycin and some of the excipients would account for a possible interaction between the mixture component. In this study, PDRX did not provide much information, since only tobramycin–thimerosal interactions could be detected. DSC and IST–FTIR are suitable and simple methods for the detection of potential incompatibilities between active pharmaceutical ingredient (API) and excipients.

     

On hölder continuity of solutions of doubly nonlinear parabolic equations with weight

We prove the Hölder regularity of bounded weak solutions of doubly nonlinear degenerate parabolic equations with measurable coefficients.     

Strongly nonlinear degenerate elliptic equations with discontinuous coefficients. II

We use energy methods to prove the existence and uniqueness of solutions of the Dirichlet problem for an elliptic nonlinear second-order equation of divergence form with a superlinear tem [i.e., g(x, u)=v(x) a(x)⋎u⋎ ^p−1u,p>1] in unbounded domains. Degeneracy in the ellipticity condition is allowed. Coefficients a _i,j(x,r) may be discontinuous with respect to the variable r. University of Catania, Italy. Published in Ukrainskii Matematicheskii Zhurnal, Vol. 49, No. 12, pp. 1601–1609, December, 1997.     

The use of accelerometers in seismic strong-motion measurements

Summary The main features of seismic strong-motion accelerometers are discussed. A complete analysis of the ?triggering process? activating the recorder shows that current devices are not best suited for this purpose and a new solution is proposed. An examination of applicability and effectiveness of spectral-analysis operation suggests that it can give misleading results. A complete analysis of errors related to the recording-integrating process of the accelerograms is made, demonstrating that this process lacks precision.

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Riassunto Si discutono gli aspetti principali delle misure accelerometriche dei moti sismici violenti. Un'analisi completa dei processi di ?triggering? che attivano il registratore mostra che gli apparati usati correntemente sono lungi dal costituire la miglior soluzione possibile e si propone qui una soluzione nuova. Un esame dell'applicabilità e dell'efficienza dell'operazione di analisi spettrale suggerisce che quest'ultima può condurre a risultati decisamente erronei. Si fa anche uno studio completo degli errori legati al processo di registrazione ed integrazione degli accelerogrammi, dimostrandone la mancanza di precisione.

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Резюме Обсуждаются основные особенности сейсмических акселерометров сильных движений. Полный анализ ?пускового процесса?, возбуждающего регистрирующий прибор, показывает, что имеющиеся приборы не являются подходящими для этой цели и предлагается новое решение. Исследование применимости и эффективности спектрального анализа указывает, что могут быть получены обманчивые результаты. Также проводится полный анализ ошибок, связанных с процессом регистрации и интегрирования акселерограмм. Отмечается, что этот процесс не обладает достаточной точностью.

     

Tensorial piezomagnetic coefficients for single-domain titanomagnetite crystals at saturation magnetization

Summary The piezomagnetic and magnetostrictive behaviour of titanomagnetite single-domain crystals is described in a general tensorial formalism with respect to a reference initial configuration in which crystals possess a saturation remanence magnetization and are subjected to a prestress field. The equivalence between the present linearized theory and previous semi-empirical formulae is proved. Numerical values are given for the piezomagnetic coefficients in terms of the magnetostrictive constants Δ₁₀₀ and Δ₁₁₁ which have been experimentally determined for titanomagnetite single crystals.

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Riassunto Si propone una descrizione generale tensoriale del piezomagnetismo e della magnetostrizione per cristalli di titanomagnetite a dominio singolo rispetto ad una configurazione iniziale di riferimento in cui i cristalli posseggono una magnetizzazione rimanente di saturazione e sono soggetti ad un campo di sforzo iniziale. Si dimostra l'equivalenza della presente teoria linearizzata e formule semiempiriche proposte precedentemente. Si forniscono valori numerici dei coefficienti piezomagnetici desunti dalle misure sperimentali delle costanti di magnetostrizione Δ₁₀₀ e Δ₁₁₁ effettuate su cristalli singoli di titanomagnetite.

     

The effect of crack interaction on the critical stress for fracture propagation in brittle materials

Summary An analytical solution is found for the stress needed for catastrophic crack propagation, by means of a model of a solid with interacting, uniformly distributed microcracks. From the experimental data for Westerly granite is is shown that the classical single-crack model may be considered a fair approximation for most purposes.

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Riassunto Si trova una soluzione analitica dello sforzo necessario per il verificarsi della propagazione catastrofica di fratture partendo da un modello di solido reale con microfratture uniformemente distribuite ed interagenti. Usando i dati sperimentali per il granito Westerly si mostra che il modello classico a frattura singola può essere considerato una buona approssimazione per molti scopi.

     

Un principio di massimo generalizzato per le sottosoluzioni deboli delle equazioni paraboliche degeneri

The aim of this paper is to prove a generalized maximum principle for weak subsolutions of second order linear degenerate-parabolic equations in divergence form, with discontinuous coefficients.     

Sottosoluzioni deboli delle equazioni paraboliche lineari del secondo ordine degeneri

We obtain sufficient conditions in order that the weak subsolution of second order linear degenerate parabolic equations turn out be upper—bounded.     

Stress drop and slip vector on a dislocation in an elastic space due to localized force distributions

Summary Some earthquake models based on the elastic theory of dislocations are presented. Earthquake occurrence is modelled as the opening of a crack in an infinite elastic medium triggered by the action of localized stress distributions. The fracture is modelled as a continuum of infinitesimal dislocations. This approach allows us to have complete information about the stress field and the displacement field and to make a first step towards understanding the relation between source mechanism and stress distributions.

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Riassunto Si presentano alcuni modelli di meccanismi sismici basati sulla teoria elastica delle dislocazioni. Un terremoto è modellato dall'apertura di una frattura in un mezzo elastico infinito causata dall'azione di distribuzioni localizzate di sforzi. La frattura è rappresentat tramite un continuo di distribuzioni infinitesime. In questo modo si possono ricavare i campi di spostamento e di sforzo causati dalla frattura. I risultati ottenuti sono intesi come un primo approccio alla comprensione dei legami fra meccanismo sismico e distribuzione dello sforzo tettonico.

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Резюме Предлагаются некоторые модели землетрясений, основанные на упругой теории дислокаций. Моделируется возникновение землетрясений, как открытие трещины в бесконечной упругой среде, инициированное действием локаликонечно малых дислокаций. Этот подход позволяет получить полную информацию о поле напряжений и поле смещений и сделать первый шаг в понимании связи мещду механизмом осточник⦎ и распределениями напрящений.

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Also at Dipartimento di Scienze della Terra dell'Università, Via della Montagnola 30, 60100 Ancona, Italia.