The influence of emulsifer concentration on the rheological properites of an oil-in-water emulsion stabilized by an anionic soap.
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Biomedical subjects
Publications and source records attributed to S S Davis.
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Targeted delivery to the gastrointestinal tract requires a multi-disciplinary approach to research involving contributions from polymer and material scientists, gastroenterologists, pharmaceutical scientists and technologists. Intestinal delivery is important not only for drugs that act locally, but also for those with systemic activity. In particular, there is considerable interest in the oral delivery of peptides and it is felt that the colon may provide an advantageous absorption site for such molecules. The different targeting mechanisms available to the pharmaceutical scientist to provide site-specific delivery in the gastrointestinal tract will be critically assessed. Delivery systems and targeting agents, which are being developed for the delivery of drugs, may also be exploited for the delivery of vaccines, since many of the delivery problems are common to both areas. Recent developments in the design of oral antigen formulations will be discussed in this review.
Microspheres based on a poly(hydroxybutyrate-hydroxyvalerate) copolymer (PHBV) (Mw = 630kD, 21% mol HV) were loaded with diazepam using different emulsion-solvent evaporation processes. Gelatin was used as a strategy to alter the release profile of the incorporated drug. The mean diameter of microspheres was from 30-40 micron. Drug-release from the microspheres over a 30-day period showed a characteristic triphasic release pattern with an initial burst effect, but was linear over the same period and without a burst effect when gelatin was used as a coating agent. Scanning electron microscopy revealed that the microspheres had different structures depending upon their method of preparation.
Modified spray drying methods, especially a novel w/o/w emulsion-spray drying method, were developed to prepare chitosan microspheres with a sustained drug release pattern. Release of the model drugs cimetidine and famotidine, from the microspheres prepared by the emulsion-spray drying methods, was greatly retarded with release lasting for several hours, compared with drug loaded microspheres prepared by conventional-spray drying or emulsion methods where drug release was almost instant. The slow release of drug was partly due to the poor wetting ability of the microspheres which floated on the surface of the dissolution medium. The addition of a wetting agent increased the release rate significantly. The coating of the microspheres with gelatin decreased the rate of release of drug in the presence of wetting agents.
The adsorption behaviour of a tetrafunctional copolymer of poly (ethylene oxide)-poly (propylene oxide) ethylene diamine (commercially available as Poloxamine 908) and a diblock copolymer of poly (lactic acid)-poly (ethylene oxide) (PLA/PEG 2:5) onto a model colloidal drug carrier (156 nm sized polystyrene latex) is described. The adsorption isotherm, hydrodynamic thickness of the adsorbed layers and enthalpy of the adsorption were assessed. The close similarity in the conformation of the poly (ethylene oxide) (PEO) chains (molecular weight 5,000 Da) in the adsorbed layers of these two copolymers was demonstrated by combining the adsorption data with the adsorbed layer thickness data. In contrast, the results from isothermal titration microcalorimetry indicated a distinct difference in the interaction of the copolymers with the polystyrene colloid surface. Poloxamine 908 adsorption to polystyrene nanoparticles is dominated by an endothermic heat effect, whereas, PLA/PEG 2:5 adsorption is entirely an exothermic process. This difference in adsorption behaviour could provide an explanation for differences in the biodistribution of Poloxamine 908 and PLA/PEG 2:5 coated polystyrene nanoparticles observed in previous studies. A comparison with the interaction enthalpy for several other PEO-containing copolymers onto the same polystyrene colloid was made. The results demonstrate the importance of the nature of the anchoring moiety on the interaction of the adsorbing copolymer with the colloid surface. An endothermic contribution is found when an adsorbing molecule contains a poly (propylene oxide) (PPO) moiety (e.g. Poloxamine 908), whilst the adsorption is exothermic (i.e. enthalpy driven) for PEO copolymers with polylactide (PLA/PEG 2:5) or alkyl moieties.
Different egg albumin microsphere systems for oral administration of paracetamol were prepared by the emulsion and capillary extrusion methods. The size of the microspheres depended on the method used to produce the microcapsules and also the size of the crystals of paracetamol. The effect of the following factors on in vitro dissolution were studied: different denaturation processes, variation in the ratio of paracetamol to albumin, size of microspheres, remnant oil in the microspheres, and the coating of the microspheres with membranes of polymethacrylates (Eudragit). The most important factors to control the release of paracetamol from the microspheres were the denaturation process and the use of waxes and membranes to delay the release of paracetamol from the microspheres. The egg albumin microspheres were very porous and permeable to water and thus the release of the paracetamol from the matrix was usually fast unless the microspheres were suitably coated, with, for example, Eudragit RL or RS.
Egg albumin microspheres containing paracetamol for oral administration were prepared and their in vivo characteristics evaluated. The egg albumin microspheres were able to improve the organoleptic characteristics of paracetamol formulations. The pharmacokinetic characteristics of three different formulations of paracetamol were evaluated in six volunteers. The formulations administered orally were: (1) Paracetamol granulated with lactose (reference), (2) Egg albumin microspheres and (3) Egg albumin microspheres coated with polymethacrylate. The pharmacokinetic characteristics for formulations 1 and 2 were similar but formulation 3 gave significant differences (p less than 0.05) in Ka, Cmax and tmax. No significant differences in relative bioavailability were observed.
Human serum albumin (HSA) microspheres have been produced in the size range of 200 nm to 10 microns by the controlled addition of acetone to an aqueous solution of HSA, followed by stabilization of the formed microspheres at an elevated temperature. Microspheres produced by this acetone-heat denaturation method could be stabilized at relatively low temperatures (75 degrees C) over a short time period (15-30 min). The acetone-heat denaturation method is different from the traditional oil/water technique for preparation of HSA microspheres, both in terms of production method and the avoidance of high temperatures (> 100 degrees C) and extended heating times (> 30 min) for stabilization. This paper describes the influence of process conditions, such as volumes of acetone and HSA concentration, on the formation of the microspheres and their morphological characteristics. A loading efficiency of 8 per cent was achieved for the HSA microspheres when using rose bengal as a model compound. The release of rose bengal from the microspheres in phosphate buffered saline at 37 degrees C was dependent on the presence of the surfactant Tween 80, and varied from a 5 per cent release in 14 days in the absence of surfactant to a 50 per cent release in 8 h in the presence of surfactant.
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