AN INVESTIGATION OF THE EFFECTS OF SOME PROCESS VARIABLES ON THE MICROENCAPSULATION OF PROPRANOLOL HYDROCHLORIDE BY THE SOLVENT EVAPORATION METHOD

The effects of four process factors: pH, emulsifier (gelatin) concentration, mixing and batch, on the % w/w entrapment of propranolol hydrochloride in ethylcellulose microcapsules prepared by the solvent evaporation process were examined using a factorial design. In this design the minimum % w/w entrapments of propranolol hydrochloride were observed whenever the external aqueous phase contained 1.5% w/v gelatin at pH 6.0 (0.71-0.91% w/w) whereas maximum entrapments occurred whenever the external aqueous phase was composed of 0.5% w/v gelatin at pH 9.0,(8.9-9.1% w/w). The theoretical maximum loading was 50% w/w. Statistical evaluation of the results by analysis of variance showed that emulsifer (gelatin) concentration and pH, but not mixing and batch significantly affected entrapment. An interaction between pH and gelatin concentration was observed in the factorial design which was accredited to the greater effect of gelatin concentration on % w/w entrapment at pH 9.0 than at pH 6.0. Maximum theoretical entrapment was achieved by increasing the pH of the external phase to 12.0. Marked increases in drug entrapment were observed whenever the pH of the external phase exceeded the pK(2) of propranolol hydrochloride. It was concluded that pH, and hence ionisation, was the greatest determinant of entrapment of propranolol hydrochloride into microcapsules prepared by the solvent evaporation process.

IMMUNOCHEMICAL AND CHROMATOGRAPHIC ANALYSES OF A NEUROPEPTIDE FROM THE MONOGENEAN PARASITE, DICLIDOPHORA-MERLANGI - EVOLUTIONARY ASPECTS OF THE NEUROPEPTIDE-Y SUPERFAMILY

1. A neuropeptide exhibiting pancreatic polypeptide-immunoreactivity (PP-IR) has been isolated and characterised from the parasitic platyhelminth, Diclidophora merlangi.

“An Examination of the Key Factor of Influence In the Development Process of Credit Union Industries,”

The aim of this paper is to analyse credit union industries within a development framework. Explicit consideration is given to credit union industries in four countries – Great Britain, Ireland, New Zealand and the United States. It is argued that in terms of a developmental typology the credit union industry in Great Britain is at a nascent stage of development, the industries in Ireland and New Zealand are at a transition stage while the US credit union industry is mature in nature. In progression between stages the analysis considers the influence of factors such as situational leadership, the complexion of trade associations, professionalisation, regulatory and legislative initiatives and technology. The analysis concluded that while there was a substantial commonality of experience, there were also significant differences in the impact of these factors. This consequently encouraged the recognition of the existence of ‘a variety of the species’ in respect of credit union development.

The Supremacy of the Sequence: Key Elements and Dimensions in the Process of Change

How single organizations manage the process of change and why only some of them are able to actually reach radical change are central questions in today’s theoretical debate. The role played by the process of change and its dimensions (namely, pace, sequence and linearity), however, has been poorly investigated. Drawing on archetype theory, this paper explores: (i) whether a specific pace of radical change exists; (ii) whether different outcomes of change are characterized by different sequences of change in key-structures and systems (iii) how the three dimensions of the process of change possibly interact. As an example of organizational change the study takes into consideration processes of accounting change in three departments of two Canadian and two Italian municipalities. The results suggest the supremacy of the sequence of implemented changes over the other two dimensions of the process in order to achieve a radical outcome of change.

Evolutionary dynamics of the spatial Prisoner's Dilemma with self-inhibition

In this paper we study the influence of interventions on self-interactions in a spatial Prisoner's Dilemma on a two-dimensional grid with periodic boundary conditions and synchronous updating of the dynamics. We investigate two different types of self-interaction modifications. The first type (FSIP) is deterministic, effecting each self-interaction of a player by a constant factor, whereas the second type (PSIP) performs a probabilistic interventions. Both types of interventions lead to a reduction of the payoff of the players and, hence, represent inhibiting effects. We find that a constant but moderate reduction of self-interactions has a very beneficial effect on the evolution of cooperators in the population, whereas probabilistic interventions on self-interactions are in general counter productive for the coexistence of the two different strategies. (C) 2011 Elsevier Inc. All rights reserved.

The agonism and synergistic potentiation of weak partial agonists by triethylamine in alpha(1)-adrenergic receptor activation: Evidence for a salt bridge as the initiating process

alpha(1)-adrenergic receptor (AR) activation is thought to be initiated by disruption of a constraining interhelical salt bridge (Porter et al., 1996). Disruption of this salt bridge is achieved through a competition for the aspartic acid residue in transmembrane domain three by the protonated amine of the endogenous ligand norepinephrine and a lysine residue in transmembrane domain seven. To further test this hypothesis, we investigated the possibility that a simple amine could mimic an important functional group of the endogenous ligand and break this alpha(1)-AR ionic constraint leading to agonism. Triethylamine (TEA) was able to generate concentration-dependent increases of soluble inositol phosphates in COS-1 cells transiently transfected with the hamster alpha(1b)-AR and in Rat-1 fibroblasts stably transfected with the human alpha(1a)-AR subtype. TEA was also able to synergistically potentiate the second messenger production by weak partial alpha(1)-AR agonists and this effect was fully inhibited by the alpha(1)-AR antagonist prazosin. However, this synergistic potentiation was not observed for full alpha(1)-AR agonists. Instead, TEA caused a parallel rightward shift of the dose-response curve, consistent with the properties of competitive antagonism. TEA specifically bound to a single population of alpha(1)-ARs with a K-i of 28.7 +/- 4.7 mM. In addition, the site of binding by TEA to the alpha(1)-AR is at the conserved aspartic acid residue in transmembrane domain three, which is part of the constraining salt bridge. These results indicate a direct interaction of TEA in the receptor agonist binding pocket that leads to a disruption of the constraining salt bridge, thereby initiating alpha(1)-AR activation.

An investigation of the influence of process and formulation variables on mechanical properties of high shear granules using design of experiment

Being able to predict the properties of granules from the knowledge of the process and formulation variables is what most industries are striving for. This research uses experimental design to investigate the effect of process variables and formulation variables on mechanical properties of pharmaceutical granules manufactured from a classical blend of lactose and starch using hydroxypropyl cellulose (HPC) as the binder. The process parameters investigated were granulation time and impeller speed whilst the formulation variables were starch-to-lactose ratio and HPC concentration. The granule properties investigated include granule packing coefficient and granule strength. The effect of some components of the formulation on mechanical properties would also depend on the process variables used in granulation process. This implies that by subjecting the same formulation to different process conditions results in products with different properties. © 2012 Elsevier B.V. All rights reserved.