Interactions between liposomes and hydroxypropylmethylcellulose.

The characteristics of the adsorption process of hydroxypropylmethylcellulose (HPMC) of molecular weight 35400 Da and nominal viscosity 100 cps onto liposomes prepared with different egg lecithin-cholesterol molar ratios were examined. Adsorption isotherms were constructed and analysed to investigate the mechanisms implicated in the incorporation of the polymer to the interface. Only the isotherms obtained with cholesterol-free liposomes were fitted with Langmuir model. When cholesterol is present in the composition they present a sigmoidal slope. The mechanism of adsorption depends on liposome composition being the main force that drives polymer adsorption of hydrophobic nature. The apparent volumes of HPMC indicate that the conformation of the adsorbed macromolecules depends on liposome composition. Hydration enthalpy values show that adsorbed polymers do not give more hydrophilic systems after freeze-drying as expected with the hydrophilic characteristics of the HPMC.

Interfacial adsorption of polymers and surfactants: implications for the properties of disperse systems of pharmaceutical interest.

This review considers basic aspects of the interfacial adsorption of polymers and surfactants, with particular reference to the relevance of these processes for the formulation of pharmaceutical disperse systems. First, we discuss different approaches to the interpretation of adsorption isotherms, paying particular attention to systems containing more than one adsorbate. Second, we consider the implications of adsorption for the properties of suspensions, emulsions, and colloidal systems, particularly as regards the use of polymers and surfactants for stabilizing disperse systems, for controlling flocculation, and for modifying the biopharmaceutical behavior of colloidal drug carriers. Finally, we present a number of representative examples of the importance of adsorption of macromolecules in pharmaceutical systems.

Degradation of hydroxypropylcellulose by Rhizomucor: effects on release from theophylline-hydroxypropylcellulose tablets.

The stability of several varieties of hydroxypropylcellulose was monitored during 3 years of storage (1) under the conditions recommended by manufacturers and official pharmacopoeias (simple storage in closed containers) and (2) at zero relative humidity. After 1 year, severe degradation of the varieties with lower initial pH and particle size stored at ambient relative humidity was shown by changes in their molecular weight and in the pH and apparent viscosity of 2% aqueous dispersions. Microbiological analyses showed the observed degradation to be attributable to the action of fungi of the genus Rhizomucor. The changes in apparent viscosity significantly affected the release of theophylline from direct compression tablets formulated with the degraded excipients.

Discrete-time backpropagation for training synaptic delay-based artificial neural networks.

The aim of this paper is to endow a well-known structure for processing time-dependent information, synaptic delay-based ANN's, with a reliable and easy to implement algorithm suitable for training temporal decision processes. In fact, we extend the backpropagation algorithm to discrete-time feedforward networks that include adaptable internal time delays in the synapses. The structure of the network is similar to the one presented by [1], that is, in addition to the weights modeling the transmission capabilities of the synaptic connections, we model their length by means of a parameter that indicates the delay a discrete-event suffers when going from Zthe origin neuron to the target neuron through a synaptic connection. Like the weights, these delays are also trainable, and a training algorithm can be derived that is almost as simple as the backpropagation algorithm, and which is really an extension of it. We present examples of the application of these networks and algorithm to the prediction of time series and to the recognition of patterns in electrocardiographic signals. In the first case, we employ the temporal reasoning characteristics of these networks for the prediction of future values in a benchmark example of a time series: the one governed by the Mackey-Glass chaotic equation. In the second case, we provide a real life example. The problem consists in identifying different types of beats through two levels of temporal processing, one relating the morphological features which make up the beat in time and another one that relates the positions of beats in time, that is, considers rhythm characteristics of the ECG signal. In order to do this, the network receives the signal sequentially, no windowing, segmentation, or thresholding are applied.

The adsorption of cellulose ethers in aqueous suspensions of pyrantel pamoate: effects on zeta potential and stability.

This work examined the physico-chemical phenomena induced in aqueous suspensions of pyrantel pamoate by two varieties of hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) of different molecular weights, and the effects of these phenomena on the physical stability of the suspension. The mechanism of the interfacial adsorption of the polymer was investigated by constructing adsorption isotherms: for the two HPMC varieties, the isotherms were of type L and were fitted with the Langmuir model; of the NaCMCs, only the variety with higher molecular weight was adsorbed, its adsorption isotherm being of type S (sigmoidal). The resulting monolayer films were characterized viscosimetrically, determining their thickness and the number of polymer molecules adsorbed per unit area. The nonionic polymers formed thinner, more continuous monolayers than the NaCMC. Only the nonionic polymers significantly altered the zeta potential of the systems. In the range of conditions studied, all the polymers stabilized the initially flocculated systems, decreasing sedimentation volume and increasing the time necessary to redisperse them (the redispersability value). This stabilization occurred either by the steric mechanism (HPMCs and the high-molecular-weight NaCMC) or by depletion mechanisms (low-molecular-weight NaCMC). Owing to the complexity of these mechanisms, sedimentation volume was not found to be a useful index of the consistency of the sediments obtained from the suspensions.

[Acquired factor VIII inhibitor in a patient with rheumatoid arthritis]. / Inhibidor adquirido del factor VIII en una paciente con artritis reumatoide.

In the present report we describe a 66 year-old-woman, diagnosed of rheumatoid arthritis, who suffered a severe haemorrhagic syndrome caused by the presence of a circulating inhibitor to factor VIII. Inhibitor quantitation was measured with Bethesda test. After treatment with corticosteroids and high-dose immunoglobulin, a good clinical response was obtained; factor VIII:C activity increased with the disappearance of detectable inhibitor. This response was observed more effectively and rapidly than with prednisone treatment alone.

[Alkyl derivatives of isoquinoline. III. Synthesis and pharmacologic activity of dialkylaminoalkyl amides of 1-chloro- and 1-methoxy-3-carboxy-4-methylisoquinoline and of 3-carboxy-2,4-dimethyl-1,2-dihydro-1-oxoisoquinoline]. / Ricerche su derivati alchilici della isochinolina. Nota III. Sintesi ed attività farmacologica di dialchilamminoalchilammidi della 1-cloro- e 1-metossi-3-carbossi-4-metilisochinolina e della 3-carbossi-2,4-dimetil-1,2-diidro-1-ossiisochinolina.

The synthesis of a series of dialkylaminoalkylic amides of 1-chloro-3-carboxy-4-methylisoquinoline (VIII), of 1-methoxy-3-carboxy-4-methylisoquinoline (VI) and of 3-carboxy-2,4-dimethyl-1-oxoisoquinoline (XIII) is described. In addition a series of 1-amino-substituted 3-carboxymethyl-4-methylisoquinolines (II) was synthesized. The pharmacological activity of some of these compounds was studied. The compounds (XIIIa), (VIa) and (VIIIa) showed a clear local anaesthetic activity, a little lower than that of lidocaine; the same compounds also showed fairly good antispasmodic properties.