4 research outputs found
Effect of processing variables and bulk composition on the surface composition of spray dried powders of a model food system
Abstract The surface compositions of food powders created from spray drying solutions containing various ratios of sodium caseinate, maltodextrin and soya oil have been analysed by Electron Spectroscopy for Chemical Analysis. The results show significant enrichment of oil at the surface of particles compared to the bulk phase and, when the non-oil components only are considered, a significant surface enrichment of sodium caseinate also. The degree of surface enrichment of both oil and sodium caseinate was found to increase with decreasing bulk levels of the respective components. Surface enrichment of oil was also affected by processing conditions (emulsion drop size and drying temperature), but surface enrichment of sodium caseinate was relatively insensitive to these. The presence of "pock marks" on the particle surfaces strongly suggests that the surface oil was caused by rupturing of emulsion droplets at the surface as the surrounding matrix contracts and hardens
Image analysis of palm oil crystallisation as observed by hot stage microscopy
This paper was accepted for publication in the journal Journal of Crystal Growth and the definitive published version is available at http://dx.doi.org/10.1016/j.jcrysgro.2016.03.026.An image processing algorithm previously used to analyse the crystallisation of a pure fat (tripalmitin) has been applied to the crystallisation of a multicomponent natural fat (palm oil). In contrast to tripalmitin, which produced circular crystals with a constant growth rate, palm oil produced speckled crystals caused by the inclusion of entrapped liquid, and growth rates gradually decreased with time. This can be explained by the depletion of crystallisable material in the liquid phase, whereas direct impingement of crystals (the basis of the Avrami equation) was less common. A theoretical analysis combining this depletion with assuming that the growth rate is proportional to the supersaturation of a crystallisable pseudo-component predicted a tanh function variation of radius with time. This was generally able to provide good fits to the growth curves. It was found that growth rate was a relatively mild function of temperature but also varied from crystal to crystal and even between different sides of the same crystal, which may be due to variations in composition within the liquid phase. Nucleation rates were confirmed to vary approximately exponentially with decreasing temperature, resulting in much greater numbers of crystals and a smaller final average crystal size at lower temperatures
Formulation, stabilisation and encapsulation of bacteriophage for phage therapy
Against a backdrop of global antibiotic resistance and increasing awareness of the importance of the
human microbiota, there has been resurgent interest in the potential use of bacteriophages for
therapeutic purposes, known as phage therapy. A number of phage therapy phase I and II clinical
trials have concluded, and shown phages don’t present significant adverse safety concerns. These
clinical trials used simple phage suspensions without any formulation and phage stability was of
secondary concern. Phages have a limited stability in solution, and undergo a significant drop in
phage titre during processing and storage which is unacceptable if phages are to become regulated
pharmaceuticals, where stable dosage and well defined pharmacokinetics and pharmacodynamics
are de rigueur. Animal studies have shown that the efficacy of phage therapy outcomes depend on
the phage concentration (i.e. the dose) delivered at the site of infection, and their ability to target and
kill bacteria, arresting bacterial growth and clearing the infection. In addition, in vitro and animal
studies have shown the importance of using phage cocktails rather than single phage preparations to
achieve better therapy outcomes. The in vivo reduction of phage concentration due to interactions
with host antibodies or other clearance mechanisms may necessitate repeated dosing of phages, or
sustained release approaches. Modelling of phage-bacterium population dynamics reinforces these
points. Surprisingly little attention has been devoted to the effect of formulation on phage therapy
outcomes, given the need for phage cocktails, where each phage within a cocktail may require
significantly different formulation to retain a high enough infective dose.
This review firstly looks at the clinical needs and challenges (informed through a review of key animal
studies evaluating phage therapy) associated with treatment of acute and chronic infections and the
drivers for phage encapsulation. An important driver for formulation and encapsulation is shelf life and
storage of phage to ensure reproducible dosages. Other drivers include formulation of phage for
encapsulation in micro- and nanoparticles for effective delivery, encapsulation in stimuli responsive
systems for triggered controlled or sustained release at the targeted site of infection. Encapsulation of
phage (e.g. in liposomes) may also be used to increase the circulation time of phage for treating
systemic infections, for prophylactic treatment or to treat intracellular infections. We then proceed to
document approaches used in the published literature on the formulation and stabilisation of phage for
storage and encapsulation of bacteriophage in micro- and nanostructured materials using freeze
drying (lyophilization), spray drying, in emulsions e.g. ointments, polymeric microparticles,
nanoparticles and liposomes. As phage therapy moves forward towards Phase III clinical trials, the
review concludes by looking at promising new approaches for micro- and nanoencapsulation of
phages and how these may address gaps in the field
Microencapsulation of Salmonella-Specific Bacteriophage Felix O1 Using Spray-Drying in a pH-Responsive Formulation and Direct Compression Tableting of Powders into a Solid Oral Dosage Form
The treatment of enteric bacterial infections using oral bacteriophage therapy can be
challenging since the harsh acidic stomach environment renders phages inactive during transit
through the gastrointestinal tract. Solid oral dosage forms allowing site-specific gastrointestinal
delivery of high doses of phages, e.g., using a pH or enzymatic trigger, would be a game changer for
the nascent industry trying to demonstrate the efficacy of phages, including engineered phages for gut
microbiome modulation in expensive clinical trials. Spray-drying is a scalable, low-cost process for
producing pharmaceutical agents in dry powder form. Encapsulation of a model Salmonella-specific
phage (Myoviridae phage Felix O1) was carried out using the process of spray-drying, employing
a commercially available Eudragit S100® pH-responsive anionic copolymer composed of methyl
methacrylate-co-methacrylic acid formulated with trehalose. Formulation and processing conditions
were optimised to improve the survival of phages during spray-drying, and their subsequent
protection upon exposure to simulated gastric acidity was demonstrated. Addition of trehalose to the
formulation was shown to protect phages from elevated temperatures and desiccation encountered
during spray-drying. Direct compression of spray-dried encapsulated phages into tablets was shown
to significantly improve phage protection upon exposure to simulated gastric fluid. The results
reported here demonstrate the significant potential of spray-dried pH-responsive formulations for
oral delivery of bacteriophages targeting gastrointestinal applications.peerReviewe