Concentric cylinder creep investigation of pharmaceutical semi-solids.
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Biomedical subjects
Publications and source records attributed to B Warburton.
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The potential for traveller's diarrhoea to impair proguanil and chloroquine absorption and cause chemoprophylaxis failure was investigated in a study involving recently returned travellers who were either asymptomatic or presented with diarrhoea. A routine dose of chemoprophylaxis was administered to 12 travellers with diarrhoea and 12 asymptomatic subjects. The subjects undertook a lactulose-mannitol intestinal permeability test and were bled hourly after prophylaxis ingestion. Plasma analysis of chloroquine and proguanil from serial samples revealed a significantly lower proguanil Cmax (146 ng/mL vs. 196 ng/mL, P = 0.05), and longer tmax (3.1 h vs. 2.6 h, P = 0.05) in the diarrhoea cohorts. The absorption coefficient was lower for proguanil (0.57 vs. 0.76) but the difference did not quite reach levels of significance. Chloroquine kinetics were similar in both groups. The diarrhoea cohort had a three-fold higher lactulose absorption, influencing the mean lactulose mannitol:ratio, 0.114 +/- 0.17 compared to the control ratio of 0.02 +/- 0.01 (P = 0.04). Symptomatic subjects had impaired mucosal function which reduced the absorption of proguanil but not chloroquine, a phenomenon which may reduce prophylactic efficacy.
The efficacy and safety of chloroquine as an antimalarial has contributed to the survival of millions in the past 50 years. Chloroquine is widely available, cheap, well tolerated and orally well absorbed. Therefore, it remains an important antimalarial drug. However, on oral administration, particularly to children, the unpleasant taste is a problem. This could be avoided by 'taste-masked and controlled release' formulations such as multiple emulsions. Although Plasmodium falciparum has developed resistance to many antimalarial drugs, including chloroquine, resistance may be attributed, among other factors, to subclinical dosage of chloroquine from administered pharmaceutical forms. This could also be relevant in the treatment of rheumatoid arthritis. Multiple W/O/W emulsions of chloroquine phosphate were prepared. Assessment of emulsion stability showed no significant change in the system. Prolonged storage (four months) of the emulsion resulted in negligible loss of chloroquine phosphate. The results suggest, therefore, that chloroquine phosphate releases due to diffusion of the drug from the internal globules and not as a consequence of instability of the W/O/W emulsion. These characteristics are in accordance with the requirements for controlled release pharmaceuticals. Stability of multiple emulsions could have resulted from interfacial polymerization or complexion between molecules. Release assessments showed faster rates for W/O/W emulsions which had smaller internal aqueous globules and, therefore, an increased interfacial area. Furthermore, transport of high-diffusion coefficient micelles could have given a greater solute flux in these systems.
Water-in-oil-in-water multiple emulsions of chloroquine diphosphate were prepared, using olive oil, arachis oil, Span 80, gelatin, acacia and Tween 80. Emulsifiers were employed individually or in combination. An attempt was made to correlate preparative variables with stability and drug release of multiple emulsions of roughly comparative particle size. When the emulsions were satisfactorily stabilized by the optimum blend of surfactants the rate of release varied with the nature and/or combination of emulsifiers employed. The possible effects of phase-inversion temperature, spontaneous emulsification and liquid crystal stabilization on the systems have been discussed. The mechanism probably involved complex interfacial adsorption and hydrodynamic phenomena in the presence of natural oils, co-surfactants and natural stabilizers of individual HLB number, particularly when acacia is present in the system. This could be attributed to the existence of protein in some species of acacia, since there are about 130 species of acacia, the gummy exudations of which are considered official in compendia. The protein content could be a reasonable additional specification for acacia as an emulsifier.
To improve the stability of w/o/w multiple emulsions of arachis and olive oil the stabilizing effect of cherry gum, in combination with acacia and gelatin, was examined. The outstanding film-forming properties of this gum having already been noted; the effect of its addition to the aqueous phases was measured by the coalescence of emulsion globules. The enhanced stability, as compared to controls, was achieved at a minimum concentration which liquid crystal-bearing interfacial films seem to appear. Creation of more coherent interfaces, inhibiting transfer of phases, could be the basis of the improved stability of the emulsion.
In this paper the commissioners of an evaluation and the researchers jointly review the relationship between research and service development at a local level in an evaluated health authority pilot project to introduce complementary therapies into primary care. The article discusses the importance of organisational arrangements between the research and the service development, focusing on the close working relationship between researchers and stakeholders in the research and corresponding service development. The relationship between the research and service development was not linear and the benefits were not based solely on outcomes of the treatment but also on the ways the evaluation gave insight into how the pilot service was delivered. Factors such as personal commitment to the project and close working relationships by all concerned are important. These elements are rarely emphasised but have to be taken into account if evidence-based health care is to achieve its potential.