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Biomedical subjects

N I Payne

Publications and source records attributed to N I Payne.

6 recordsLinked to original sources

Differential scanning calorimetry characterization of process-induced variations in an ointment base.

Preparation of an experimental emollient wax-gelled ointment base by two processes differing only in cooling rate produced material with markedly different physical properties. Differential scanning calorimetry showed that a major endotherm, possibly related to a phase change in a major triglyceride wax component, Synchrowax HGLC, was different in the two products. Mean enthalpies for this major endotherm for the two products were 7.36 J g-1 (s.d. = 0.49, n = 5) in slow cooled samples and 4.35 J g-1 (s.d. = 0.21, n = 5) in fast cooled samples. The degree of order of the Synchrowax HGLC in the ointment is suggested as being different in the two preparations and it is this that controls the physical properties of the ointment.

Calorimetry, Differential Scanning↗

In-vivo studies of amphotericin B liposomes derived from proliposomes: effect of formulation on toxicity and tissue disposition of the drug in mice.

The repeat dose toxicity of various liposomal formulations containing amphotericin B has been determined in mice. In general, small liposomes (e.g. 100-150 nm) were found to be more toxic than their large counterparts (e.g. about 2000 nm). However, the repeat dose toxicity of small liposomes could be diminished substantially by the inclusion of sterol (i.e. ergosterol) into the liposomal membranes. Tissue accumulation studies of amphotericin B after repeat dosing may be a useful adjunct to formulation development.

Amphotericin B↗

Delineation of the spleen by a combination of proliposomes with water-soluble contrast media: an experimental study using computed tomography.

Numerous methods for delineating the splenic pulp, including dynamic computed tomography scanning, either are unreliable or have other shortcomings. A method is described for enhancing the spleen using aqueous contrast media in conjunction with proliposomes. While liposomal carrier systems have previously been used for diagnostic purposes, proliposomes circumvent many of the problems associated with the manufacture and handling of liposomes. This enhancement is based on the selective uptake of particulate material by the reticuloendothelial system. While others, by using washed liposomal suspensions, have apparently obtained higher degrees of splenic contrast enhancement, the present study nevertheless shows that significant levels of enhancement are obtainable by a combination of intra- and extraliposomal contrast media.

Animals↗

Proliposomes: a novel solution to an old problem.

A procedure is described for the preparation of a dry, free-flowing granular product which, on addition of water, disperses/dissolves to form an isotonic liposomal suspension, suitable for administration either intravenously or by other routes. Various parameters have been investigated including the suitability of sorbitol and sodium chloride as carrier materials, the nature of the lipid(s) in the formulation, and the extent of lipid loading onto the carrier. These factors are shown to have a marked effect on both the dry product and the hydrated liposomes.

Amphotericin B↗

Characterization of proliposomes.

Photographic evidence of the process of proliposome hydration is provided together with comprehensive particle size analysis of both hydrated dimyristoylphosphatidylcholine: dimyristoylphosphatidylglycerol:ergosterol:amphotericin B proliposomes and egg lecithin:ergosterol:amphotericin B proliposomes using photon correlation spectroscopy and Coulter Counter analysis. Proliposome particle size and the temperature during hydration have been shown to have little effect on subsequent liposome size. A short term stability study of proliposomes indicated that only minor changes in the size distribution profile of the hydrated product are apparent after storage at 20 degrees C for 9 months. Furthermore, no drop in amphotericin B potency was noticed over a 6-month period.

Amphotericin B↗

Development of a parenteral formulation of trimelamol, a synthetic S-triazine carbinolamine-containing cytotoxic agent.

Trimelamol is a synthetic s-triazine carbinolamine-containing agent exhibiting poor aqueous solubility and stability characteristics. The present studies were conducted to provide a stable parenteral dosage form of trimelamol, which could be used for clinical evaluation of the drug and also be manufactured on a commercial scale without undue drug decomposition occurring. Solubility and stability of trimelamol were found to increase in the presence of aqueous-polyethylene glycol (PEG) solutions of increasing average PEG molecular weight (up to mol wt = 1000); PEG 1000 (75%) in water provided the optimum formulation vehicle. In contrast to the optimum liquid formulation of the drug (detailed above) it was necessary to make various compromises to the formulation in terms of drug solubility and stability, because of the problems encountered in processing (e.g., sterile filtration, lyophilization, and reconstitution). Freeze-drying of the formulation extended the product shelf-life relative to the liquid formulation. Differential Scanning Colorimetry (DSC) studies, to determine the freeze-drying cycle parameters, showed that the freezing and melting characteristics of the trimelamol-PEG formulations were dependent upon the rate of cooling, as well as the concentration and average molecular weight of PEG used. The prototype containing 30 mg/mL trimelamol in a 50% PEG 3400-aqueous vehicle was found to be the optimal formulation for sterile filtration, lyophilization, and subsequent reconstitution. Through the use of in vitro techniques, the possibility of hemolysis occurring upon injection resulting from the inclusion of high molecular weight PEGs in the vehicle, was shown to be unlikely.

Animals↗