Papers by David Fairhurst
In life-cycle management of pharmaceutical products, novel drug delivery technologies that offer ... more In life-cycle management of pharmaceutical products, novel drug delivery technologies that offer positive differentiation over first-generation products provide an important means for staying competitive in today’s business environment. This article will briefly discuss a proven and scalable solid dispersion approach based on spray-drying that is suitable for Biopharmaceutical Classification System (BCS) (Figure 1) Class II active pharmaceutical ingredients (APIs) and new chemical entities (NCEs).1-4 Many existing APIs and NCEs are poorly water soluble and subsequently have low oral bioavailability if formulated in unmodified form. Traditional approaches to overcoming this include (1) improvement of water miscibility by employing self-emulsification, lipid-based techniques, solubilization into micellar cores, or alternatively complexation with cyclodextrins; (2) reduction of particle size to nano-scale via mechanical milling or high-shear processing accompanied by particle stabiliza...
Nanoscale particle sizing of colloidal suspensions can be performed with Acorn,™ a new, patented ... more Nanoscale particle sizing of colloidal suspensions can be performed with Acorn,™ a new, patented handheld device, that combines remote delivery and detection of laser light, and a direct measurement of particle size, without the use of digital correlators. The former is achieved through a singlemode backscatter fiber optic probe, while the latter is made possible through the implementation of a statistical processing algorithm, which recovers the average particle diameter from the integration time dependent coherence of the scattered intensity. Real-time measurement of the factorial moments, or the coherence of the scattered intensity, is made with a field programmable gate array. A fiber optic backscatter probe permits remote interrogation of samples either by dipping the probe into the solution or by placing the probe outside the container. Acorn™ provides a rapid measurement of the average diameter in the range of 2 to 5000 nm over a broad range of concentrations.
Clay Minerals, 1993
Modem disc centrifuge technology has extended the range of application of sedimentation particle ... more Modem disc centrifuge technology has extended the range of application of sedimentation particle size analysis to include the submicron region. An overall size range of approximately 10 nm to 100 pm is now accessible. The principles of both the disc centrifuge photosedimentometer, which employs optical detection with full Mie light scattering corrections, and the X-ray disc centrifuge are described. Examples of their application to a variety of samples are given to illustrate the performance characteristics of the instruments including a direct comparison of resolving power with that of the laser diffraction technique.
Colloid and Polymer Science
The selection of appropriate solvents into which carbon blacks can be dispersed optimally is impo... more The selection of appropriate solvents into which carbon blacks can be dispersed optimally is important for product manufacture and performance. Molecular-level interactions determine solvent suitability but are difficult to measure; existing experimental approaches require slow/expensive tests of dispersion stability. NMR solvent relaxation measurements are shown to be a fast indicator of solvent suitability, with sensitivity to the solvent-particle intermolecular forces making it a reliable proxy for determining optimum dispersibility. A structured approach to relaxation measurements with a selection of both good and poor solvents yields the Hansen solubility parameters (HSP) for the particle surface. Once obtained, suitable solvents (or solvent mixtures) can be selected from a database of HSP values to match the particle interface. The application of the NMR solvent relaxation approach for determining the HSP values is illustrated for a commercially available carbon black. Further...
Consistency in the stability/structure characteristics of an emulsion is a necessary prerequisite... more Consistency in the stability/structure characteristics of an emulsion is a necessary prerequisite to achieve the desired final product quality. Two reliable and well-established parameters that are intimately related to the physical stability and structure of an emulsion are particle (droplet) size and zeta potential (surface charge). Topical delivery systems (TDS) are many and varied; they include creams and lotions based on O/W and W/O emulsions. TDS are complex, multicomponent, heterogeneous compositions that require much iteration to attain the final desired formulation; many factors Cosmetic Delivery Systems Acoustic Attenuation Spectroscopy 24 play a role in determining the outcome. Additionally, cosmetic and pharmaceutical emulsions cannot be diluted without consequence to the droplet size and, hence stability. Additionally, product performance behavior such as delivery of actives, efficacy (e.g. SPF) and aesthetic acceptability (e.g. spreading) is directly affected by the dr...
Skin, hair and mucosal surfaces are useful targets for the delivery of active compounds, botanica... more Skin, hair and mucosal surfaces are useful targets for the delivery of active compounds, botanicals and, importantly, drugs. Encapsulation provides an invaluable tool to the cosmetic and/or pharmaceutical formulator, providing great flexibility in the choice of delivery mechanisms and excipients that can be used. Dispersions of solid lipid nanoparticles (SLNs) were prepared using biodegradable materials generally regarded as safe by a melt-emulsify-chill (MEC) method. Among the materials encapsulated in SLNs were hydrophobic active pharmaceutical ingredients, antiviral and fungicidal compounds, organic UV absorbers and fluorescent dyes. The loading, adhesion and intracellular localization of the SLNs were studied as a function of surface charge. The MEC process can easily, and cheaply, produce a range of solid lipid nanoparticles (SLNs) “smart colloids” that offer flexibility in formulation, increased efficacy and decreased formulation complexity. The method is general and can be ap...
Induction of humoral responses to HIV at mucosal compartments without inflammation is important f... more Induction of humoral responses to HIV at mucosal compartments without inflammation is important for vaccine design. We developed charged wax nanoparticles that efficiently adsorb protein antigens and are internalized by DC in the absence of inflammation. HIV-gp140-adsorbed nanoparticles induced stronger in vitro T-cell proliferation responses than antigen alone. Such responses were greatly enhanced when antigen was co-adsorbed with TLR ligands. Immunogenicity studies in mice showed that intradermal vaccination with HIV-gp140 antigen-adsorbed nanoparticles induced high levels of specific IgG. Importantly, intranasal immunization with HIV-gp140-adsorbed nanoparticles greatly enhanced serum and vaginal IgG and IgA responses. Our results show that HIV-gp140-carrying wax nanoparticles can induce strong cellular/humoral immune responses without inflammation and may be of potential use as effective mucosal adjuvants for HIV vaccine candidates.
TEXT 1International Partnership for Microbicides, Silver Spring, United States of America, 2St Ge... more TEXT 1International Partnership for Microbicides, Silver Spring, United States of America, 2St George’s, University of London, United Kingdom, 3University of Bristol, Bristol, United Kingdom, 4Brookhaven Instruments Inc., Holtsville, United States of America Background: A variety of polyanionic compounds have been shown to be useful in topical microbicide formulations. These compounds are thought to work through similar mechanisms of action (e.g. binding via an electrostatic interaction to positively-charged V3 loop of gp120). However, these compounds vary greatly from each other in many physico-chemical features including structure of the hydrophobe, charge density and, importantly, MWt and MWt distribution. Each of these factors impinge on the efficacy of binding to any sterically-restricted surface including gp120. These compounds all carry a negative-charge at neutral pH, however variation in the magnitude of the surface charge over the pH range encompassing vaginal fluid and se...
Cosmetics and Toiletries, 1995
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Papers by David Fairhurst