Paul Royall | King's College London (original) (raw)

Papers by Paul Royall

International Journal of Pharmaceutics, Sep 1, 2005

The aim of this short study was to develop a novel method of sample presentation that will allow ... more The aim of this short study was to develop a novel method of sample presentation that will allow currently available DMA apparatus designed for the testing of self-supporting materials to detect amorphous content in controlled mixtures of amorphous and crystalline powders. The preparation of amorphous lactose was carried out by spraying drying, using a Büchi mini spray drier. Controlled mixtures of amorphous and crystalline lactose were produced to give eight samples ranging between 2% and 75% (w/w) amorphous content. These powdered mixtures were loaded into the DMA using a novel powder-pocket device, which consisted of folded sheet of stainless steel. The pocket was clamped directly into the DMA using a single cantilever configuration, and subjected to oscillating displacement, forcing horizontal shearing of the powder between the two plates of the pocket. Typical experimental parameters were a dynamic displacement of 0.05 mm with a frequency of 1 Hz and a heating rate of 5 • C/min, from 25 • C to 250 • C. Over the glass transition region of amorphous lactose, the storage modulus decreased rapidly and a peak was observed in the tan δ signal, which are typical DMA responses for self-supporting glassy materials over their glass transition region. In both the storage modulus and tan δ signals, contributions from both plasticized and non-plasticized amorphous lactose were demonstrated. Such an observation was caused by the powder pocket restricting the loss of the 2.5% (w/w) water present in the spray-dried lactose within the time scale of the first heating cycle. The tan δ peak for the non-plasticized amorphous lactose showed Arrhenius behaviour as function of oscillation frequency. The relationship between the increase in the tan δ peak with increasing frequency allowed the determination of an activation energy that was comparable to the literature values for similar compounds. The height of the tan δ peak for the non-plasticized material was directly proportional to the amount of amorphous lactose present in the mixtures. The glass transition response was still detectable in mixtures containing as little as 2% (w/w) amorphous content, however the theoretical limit of detection was higher than that determined for the same mixtures using solution calorimetry. The results demonstrate that the novel powder pocket allows the use of conventional DMA instruments for the analysis of pharmaceutical powders, however the technique requires more development to further reduce its theoretical limit of detection.

Langmuir, May 8, 2018

This document is confidential and is proprietary to the American Chemical Society and its authors... more This document is confidential and is proprietary to the American Chemical Society and its authors. Do not copy or disclose without written permission. If you have received this item in error, notify the sender and delete all copies. Glycerol solvates DPPC headgroups and localises in the interfacial regions of model pulmonary interfaces altering bilayer structure

Pharmaceutical Science & Technology Today, May 1, 1999

Current Pharmaceutical Biotechnology, Jun 1, 2005

International Journal of Pharmaceutics, 2004

Solution calorimetry has been used in a number of varying applications within pharmaceutical rese... more Solution calorimetry has been used in a number of varying applications within pharmaceutical research as a technique for the physical characterisation of pharmaceutical materials, such as quantifying small degrees of amorphous content, identifying polymorphs and investigating interactions between drugs and carbohydrates or proteins and carbohydrates. A calibration test procedure is necessary to validate the instrumentation; a few of the suggested calibration reactions are the enthalpies of solution associated with dissolving Tris in 0.1 M HCl or NaCl, KCl or propan-1-ol in water. In addition, there are a number of different methods available to determine enthalpies of solution from the experimental data provided by the calorimeter, for example, the Regnault-Pfaundler's method, a graphical extrapolation based on the Dickinson method, or a manual integration-based method. Thus, the aim of the study was to investigate how each of these methods influences the values for the enthalpy of solution. Experiments were performed according to the method outlined by Hogan and Buckton [Int. J. Pharm. 207 (2000) 57] using KCl (samples of 50, 100 and 200 mg), Tris and sucrose as calibrants. For all three materials the manual integration method was found to be the most consistent with the KCl in water (sample mass of 200 mg) being the most precise. Thus, this method is recommended for the validation of solution calorimeters.

ABSTRACT Die Bestimmung des Kristallinitatsgrades von Arzneimitteltragern stellt bei der Entwickl... more ABSTRACT Die Bestimmung des Kristallinitatsgrades von Arzneimitteltragern stellt bei der Entwicklung von neuen Medikamenten ein wichtiges Kriterium dar. Neben spektrometrischen und röntgenographischen Methoden werden zumeist als thermoanalytisches Verfahren nur die Kalorimetrie eingesetzt. Neuartig ist die Nutzung der Dynamisch-Mechanischen Thermoanalyse (DMA) fur diese Anwendungsfragen. Die neu entwickelte, patentierte Probenhalterung fur Pulver ermöglicht nun eine sichere und zur DSC mehr als 50 Mal empfindlicheren Charakterisierung von amorphen Strukturen.

Thermochimica Acta, Jul 1, 2004

A thermal analysis of the effect of hydration of non-aqueous polymer-stabilised gels was investig... more A thermal analysis of the effect of hydration of non-aqueous polymer-stabilised gels was investigated using differential scanning calorimetry (DSC). The interaction of water with the polymer and its distribution within the gel are critical to the physicochemical behaviour of the gel, and consequently affects the utility of the gel matrix as a drug delivery vehicle. Addition of water at levels up to and including 50% (w/w) did not result in an observable freezing event in the thermogram. However, at 60 and 80% (w/w) water, phase transitions were observed, the magnitude of which were found to be independent of the annealing time within the range used. The observed melting enthalpies increased as the water concentration increased for all formulations, but were always smaller than that of pure water. There was no evidence of multiple transitions that might be attributed to different populations of water molecules. However, the results demonstrate that DSC can be employed to differentiate between freezable and non-freezable water, in these particular formulations.

Journal of Nanoscience and Nanotechnology, Nov 1, 2021

Polyelectrolyte multilayers are promising drug carriers with potential applications in the delive... more Polyelectrolyte multilayers are promising drug carriers with potential applications in the delivery of poorly soluble drugs. Furthermore, the polyelectrolyte multilayer contributes towards electrostatic interactions, which enhances the physical and chemical stability of colloids when compared to those prepared by other approaches. The aim of this work was to generate a polyelectrolyte multilayer on well characterised nanoparticles of the poorly water-soluble drug, griseofulvin. Griseofulvin (GF) nanoparticles (300 nm) were produced by wet bead milling, bearing a negative surface charge due to the use of poly(sodium 4-styrenesulfonate) (PSS) as a stabiliser. Six further layers of alternating chitosan and PSS polyelectrolyte multilayer were successfully generated at the particle surface either via use of: (1) the conventional method of adding excess coating polymer followed by centrifugation, or (2) the continuousin situapproach of adding sufficient amount of coating polymer. The continuousin situmethod was designedde novoby the consecutive addition of polymers under high shear rate mixing. In comparison to the continuousin situmethod, the conventional method yielded nanoparticles of smaller size (282 ±9 nm vs. 497 ±34 nm) and higher stability by maintaining its size for 6 months. In conclusion, the parent griseofulvin nanosuspension proved to be a suitable candidate for the polyelectrolyte multilayer fabrication providing an avenue for a bespoke formulation with versatile and potentially enhanced drug delivery properties.

European Pharmaceutical Review, Oct 1, 2019

SIGLEAvailable from British Library Document Supply Centre-DSC:DXN030722 / BLDSC - British Librar... more SIGLEAvailable from British Library Document Supply Centre-DSC:DXN030722 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Drones, Oct 9, 2020

Anaphylaxis is a life-threatening condition where delays in medical treatment can be fatal. Such ... more Anaphylaxis is a life-threatening condition where delays in medical treatment can be fatal. Such situations would benefit from the drone delivery of an adrenaline auto-injector such as EpiPen ®. This study evaluates the potential risk, reward, and impact of drone transportation on the stability of adrenaline during episodes of anaphylaxis. Further, this study examines pharmacists' perceptions on drone delivery-pharmacists approved the use of drones to deliver EpiPen ® during emergencies but had concerns with drone safety and supply chain security. Laboratory simulated onboard drone conditions reflected typical missions. In these experiments, in vitro model and pharmaceutical equivalent formulations were subjected independently to 30 min vibrations at 5, 8.43, and 13.33 Hz, and temperature storage at 4, 25, 40, and 65 • C for 0, 0.5, 3, and 24 h. The chiral composition (an indicator of chemical purity that relates to molecular structure) and concentration of these adrenaline formulations were determined using ultraviolet (UV) and circular dichroism spectroscopy (CD). Adrenaline intrinsic stability was also explored by edge-of-failure experimentation to signpost the uppermost limits for safe transportation. During drone flight with EpiPen ® , the temperature and vibration g-force were 10.7 • C and 1.8 g, respectively. No adverse impact on adrenaline was observed during drone flight and laboratory-simulated conditions shown by conformation to the British Pharmacopeia standards (p > 0.05 for CD and UV). This study showed that drone delivery of EpiPen ® is feasible. There are more than 15,000 community pharmacies and ≈9000 GP surgeries spanning the UK, which are likely to provide achievable ranges and distances for the direct drone delivery of EpiPen ®. The authors recommend that when designing future missions, in addition to medicine stability testing that models the stresses imposed by drone flight, one must conduct a perceptions survey on the relevant group of medical professionals, because their insights, acceptance, and concerns are extremely valuable for the design and evaluation of the mission.

European Pharmaceutical Review, Jun 1, 2017

This study investigated the stability of solid lactose stored under high temperature and humidity... more This study investigated the stability of solid lactose stored under high temperature and humidity conditions.

Journal of Pharmacy and Pharmacology, 2002

Thermal analysis equipment can be found in nearly all of the analytical, development, formulation... more Thermal analysis equipment can be found in nearly all of the analytical, development, formulation and QA laboratories within the pharmaceutical industry. However, these work horse instruments are learning to run faster and to analyse an ever more varied field of samples.

Journal of Pharmacy and Pharmacology, 2003

International Journal of Pharmaceutics, Apr 1, 2009

The use of a new sample holder for dynamic mechanical analysis (DMA) as a means to characterise t... more The use of a new sample holder for dynamic mechanical analysis (DMA) as a means to characterise the T g of powdered hydroxypropyl methyl cellulose (HPMC) has been investigated. A sample holder was constructed consisting of a rectangular stainless steel container and a lid engineered to fit exactly within the walls of the container when clamped within a TA instruments Q800 DMA in dual cantilever configuration. Physical mixtures of HPMC (E4M) and aluminium oxide powders were placed in the holder and subjected to oscillating strains (1 Hz, 10 Hz and 100 Hz) whilst heated at 3 • C/min. The storage and loss modulus signals showed a large reduction in the mechanical strength above 150 • C which was attributed to a glass transition. Optimal experimental parameters were determined using a design of experiment procedure and by analysing the frequency dependence of T g in Arrhenius plots. The parameters were a clamping pressure of 62 kPa, a mass ratio of 0.2 HPMC in aluminium oxide, and a loading mass of either 120 mg or 180 mg. At 1 Hz, a T g of 177 ± 1.2 • C (n = 6) for powdered HPMC was obtained. In conclusion, the new powder holder was capable of measuring the T g of pharmaceutical powders and a simple optimization protocol was established, useful in further applications of the DMA powder holder.