Publications by authors named "Barbara R Conway"

58 Publications

Drug Delivery Approaches for Managing Overactive Bladder (OAB): A Systematic Review.

Pharmaceuticals (Basel) 2021 Apr 26;14(5). Epub 2021 Apr 26.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK.

Overactive bladder syndrome (OAB) is characterised by urgency symptoms, with or without urgency incontinence, usually with frequency and nocturia and severely affects the quality of life. This systematic review evaluates the various drug delivery strategies used in practice to manage OAB. Advanced drug delivery strategies alongside traditional strategies were comprehensively analysed and comparatively evaluated. The present review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines. A total of 24 studies reporting the development of novel formulations for the treatment of OAB were considered eligible and were further categorised according to the route of drug administration. The review found that various drug delivery routes (transdermal, intravesicular, oral, vaginal and intramuscular) are used for the administration of drugs for managing OAB, however, the outcomes illustrated the marked potential of transdermal drug delivery route. The findings of the current review are expected to be helpful for pharmaceutical scientists to better comprehend the existing literature and challenges and is anticipated to provide a basis for designing and fabricating novel drug delivery systems to manage OAB.
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http://dx.doi.org/10.3390/ph14050409DOI Listing
April 2021

Topical Antiseptic Formulations for Skin and Soft Tissue Infections.

Pharmaceutics 2021 Apr 15;13(4). Epub 2021 Apr 15.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK.

Skin and soft tissue infections (SSTIs) are usually acute conditions of inflammatory microbial occupation of the skin layers and underlying soft tissues. SSTIs are one of the most frequent types of infection, typically requiring medical intervention and contribute to morbidity and mortality in both primary care and hospitalised patients. Due to the dramatic rise of antibiotic resistance, antiseptic agents can be potential alternatives for the prevention and treatment of SSTIs. Notably, they are commonly recommended in many global practical guidelines for use in per- and post- operative procedures. A range of antiseptics, including chlorhexidine, triclosan, alcohol, and povidone-iodine, are used and are mainly formulated as traditional, simple dosage forms such as solutions and semi-solids. However, in recent years, there have been studies reporting the potential for nanotechnology in the delivery of antiseptics. In this review, we have collated the scientific literature that focuses on topical antiseptic formulations for prevention and treatment of SSTIs, and have divided findings into traditional and advanced formulations. We conclude that although nanotechnological formulations have demonstrated potential advantages for delivering drugs; nevertheless, there is still scope for traditional formulations and further development of optimised topical formulations to address the rise of antimicrobial resistance.
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http://dx.doi.org/10.3390/pharmaceutics13040558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071503PMC
April 2021

An assessment of the impact of the vaccination program on coronavirus disease 2019 (COVID-19) outbreaks in care homes in Northern Ireland-A pilot study.

Infect Control Hosp Epidemiol 2021 Apr 15:1-2. Epub 2021 Apr 15.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom.

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http://dx.doi.org/10.1017/ice.2021.169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111199PMC
April 2021

Analysis of hospital antimicrobial consumption to identify targets for antimicrobial stewardship.

Infect Control Hosp Epidemiol 2021 Apr 12:1-3. Epub 2021 Apr 12.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom.

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http://dx.doi.org/10.1017/ice.2021.126DOI Listing
April 2021

Impact of antimicrobial stewardship interventions on reducing antifungal use in hospitals in Jordan.

Infect Control Hosp Epidemiol 2021 Apr 6:1-2. Epub 2021 Apr 6.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom.

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http://dx.doi.org/10.1017/ice.2021.105DOI Listing
April 2021

Magnesium aluminium silicate-metformin hydrochloride complexes - The use of isothermal calorimetry in probing the understanding of clay and drug nanocomplexations.

Curr Drug Deliv 2021 Apr 2. Epub 2021 Apr 2.

School of Applied Sciences, Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield. United Kingdom.

This study reports the use of Isothermal Calorimetry (ITC) in understanding the complexation process occurring between Magnesium Aluminium Silicate (MAS) and metformin hydrochloride (MET), as a potential controlled release drug delivery system. The calorimetric results confirmed the binding between MET and MAS at various pHs (5, 7 and 9) and temperatures (25 ºC and 37 ºC). The overall change in enthalpy was found to be exothermic with a comparatively small entropic contribution to the total change in Gibbs free energy, implying that the binding was an enthalpically driven process. These findings suggest that the binding process was dominated by hydrogen bonding and electrostatic interactions. pH and temperature variation did not have a great impact on the binding, as observed from the similarity in enthalpy (ΔH), entropy (ΔS) or Gibbs free energy (ΔG), with the reaction being only slightly more exothermic at pH 5 and at 37 ºC. MAS and MET complex dispersions and particles were also formulated and analysed successfully using DSC, XRPD, ATR-FTIR, SEM/EDX, digital microscopy. 2D-SAXS. 2D-SAXS was able to differentiate between MAS particulates and MAS-MET complexes when analysed in their liquid form suggesting the importance of appropriate methodology and instrumentation used in characterisation.
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http://dx.doi.org/10.2174/1567201818666210402125244DOI Listing
April 2021

Application of Focus Variation Microscopy and Dissolution Imaging in Understanding the Behaviour of Hydrophilic Matrices.

Pharmaceutics 2020 Nov 28;12(12). Epub 2020 Nov 28.

Department of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, UK.

Hydrophilic matrix systems can be found in a wide range of extended release pharmaceutical formulations. The main principle of these systems is that upon contact with water, the hydrophilic component swells to form a hydrated gel layer which controls drug release. The following work demonstrates an explorative study into the use of dissolution imaging and focus variation microscopy with hydrophilic polymers. This study investigated the surface properties of xanthan gum (XG), polyethylene oxide (PEO), and hypromellose (hydroxypropyl methylcellulose, HPMC) compacts with each of these three hydrophilic polymers from one of each classification of natural, semi-synthetic, or synthetic polymer using a focus variation instrument. The auto correlation length (S) showed all surface profiles from the compacts displayed a value below 0.1 mm, indicating that only high frequency components (i.e., roughness) were considered and that the analysis had been successful. The developed interfacial area ratio (S) displayed values below 5% in line with ISO guidelines for all the polymers studied with their texture aspect ratio values (S) > 0.5, indicating uniformity of the surfaces of the produced compacts. Of the various parameters studied, areal material ratio (S2) predicted XG to wet and hydrate quicker than PEO, with PEO also wetting and hydrating quicker than the HPMC. The dissolution imaging and initial swelling studies proved to concur with the findings from the areal material ratio (S2) parameter, suggesting porosity was not an indicator for the ease with which water ingress occurs. This study suggests the S surface parameter to potentially predict wetting and initial hydration of hydrophilic polymers, however care should be taken as this study consists of a selected number of hydrophilic polymers.
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http://dx.doi.org/10.3390/pharmaceutics12121162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759878PMC
November 2020

Impact of an antimicrobial stewardship programme on reducing broad-spectrum antibiotic use and its effect on carbapenem-resistant Acinetobacter baumannii (CRAb) in hospitals in Jordan.

J Antimicrob Chemother 2021 Jan;76(2):516-523

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, UK.

Objectives: To evaluate the impact of an antimicrobial stewardship programme (ASP) on reducing broad-spectrum antibiotic use and its effect on carbapenem-resistant Acinetobacter baumannii (CRAb) in hospitalized patients.

Methods: The study was a retrospective, ecological assessment in a tertiary teaching hospital over 6 years (January 2014 to December 2019). The intervention involved the implementation of an ASP in February 2018, which remains in effect today. This ASP consists of several components, including education, antibiotic guidelines, antibiotic restriction policy with prior approval, audit of compliance to the restriction policy and feedback. Restricted antibiotics were imipenem/cilastatin, ertapenem, meropenem, vancomycin, teicoplanin, tigecycline, colistin, amikacin, piperacillin/tazobactam, levofloxacin and ciprofloxacin. The intervention was evaluated by time-series methods.

Results: Statistically significant decreases in the level of antibiotic use, after the introduction of the ASP, were observed for the following antibiotics: imipenem/cilastatin (P = 0.0008), all carbapenems (P = 0.0001), vancomycin (P = 0.0006), colistin (P = 0.0016) and third-generation cephalosporins (P = 0.0004). A statistically significant decrease in the slope, after the introduction of the ASP, for ertapenem (P = 0.0044) and ciprofloxacin (P = 0.0117) was observed. For piperacillin/tazobactam, there was a significant increasing trend (P = 0.0208) before the introduction of the ASP. However, this increased trend was halted post-introduction of the ASP (P = 0.4574). The introduction of the ASP was associated with a significant impact on reducing the levels of CRAb (P = 0.0237).

Conclusions: The introduced antimicrobial stewardship interventions contributed to a reduction in the use of several broad-spectrum antibiotics, reversed the trends of increasing use of other antibiotics and were associated with a significant reduction in CRAb.
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http://dx.doi.org/10.1093/jac/dkaa464DOI Listing
January 2021

Identification of thresholds in relationships between specific antibiotic use and carbapenem-resistant Acinetobacter baumannii (CRAb) incidence rates in hospitalized patients in Jordan.

J Antimicrob Chemother 2021 Jan;76(2):524-530

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, UK.

Background: Antibiotic resistance is a major threat to public health worldwide. The relationship between the intensity of antibiotic use and resistance might not be linear, suggesting that there might be a threshold of antibiotic use, beyond which resistance would be triggered.

Objectives: To identify thresholds in antibiotic use, below which specific antibiotic classes have no significant measurable impact on the incidence of carbapenem-resistant Acinetobacter baumannii (CRAb), but above which their use correlates with an increase in the incidence of CRAb.

Methods: The study took place at a tertiary teaching hospital in Jordan. The study was ecological in nature and was carried out retrospectively over the period January 2014 to December 2019. The outcome time series for this study was CRAb cases. The primary explanatory variables were monthly use of antibiotics and the use of alcohol-based hand rub (ABHR). Non-linear time-series methods were used to identify thresholds in antibiotic use.

Results: Non-linear time-series analysis determined a threshold in third-generation cephalosporin and carbapenem use, where the maximum use of third-generation cephalosporins and carbapenems should not exceed 8 DDD/100 occupied bed days (OBD) and 10 DDD/100 OBD, respectively. ABHR had a significant reducing effect on CRAb cases even at lower usage quantities (0.92 L/100 OBD) and had the most significant effect when ABHR exceeded 3.4 L/100 OBD.

Conclusions: The identification of thresholds, utilizing non-linear time-series methods, can provide a valuable tool to inform hospital antibiotic policies through identifying quantitative targets that balance access to effective therapies with control of resistance. Further studies are needed to validate the identified thresholds, through being prospectively adopted as a target for antimicrobial stewardship programmes, and then to evaluate the impact on reducing CRAb incidence.
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http://dx.doi.org/10.1093/jac/dkaa463DOI Listing
January 2021

Surveillance study of asymptomatic and presymptomatic coronavirus disease 2019 (COVID-19) in care homes in Northern Ireland.

Infect Control Hosp Epidemiol 2020 Oct 20:1-3. Epub 2020 Oct 20.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom.

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http://dx.doi.org/10.1017/ice.2020.1284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653223PMC
October 2020

Imaging of the Effect of Alcohol-Containing Media on the Performance of Hypromellose Hydrophilic Matrix Tablets: Comparison of Direct Compression and Regular Grades of Polymer.

Pharmaceutics 2020 Sep 18;12(9). Epub 2020 Sep 18.

Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.

As the ingestion of drug products with alcohol could have adverse effects on the release of drugs from dosage forms, it is important to understand the mechanisms underpinning the influence on drug release by evaluating the effect of alcohol-containing media on the behaviour of pharmaceutical excipients. In this work, the effect of hydroalcoholic media containing up to 40% / absolute ethanol was evaluated, employing both the regular (CR) and direct compression grades (DC) of hypromellose. X-ray microtomography (XµT) and magnetic resonance imaging (MRI) were used as complementary techniques in determining the influence of the media composition on the ability of the CR and DC polymers to form and evolve the gel layer that controls drug release. Particle and powder properties of the polymer were characterised to determine any relationship to performance in hydroalcoholic media. Triboelectrification results showed the CR grade formulation to charge electropositively whereas the DC grade charged electronegatively. The flow properties also showed the DC grade to have a superior flow as compared to its CR counterpart. Differences in particle morphology between the grades influenced charging and flow behaviour of the powders; however, it did not seem to impact significantly either on the mechanical strength or the drug release properties of the compacted formulation using the model drug propranolol HCl. XµT and MRI imaging were successfully used as complementary techniques in determining the gel layer/hydration layer thickness measurements as the layer developed, as well as following ingress of hydroalcoholic media and its impact on the dry core. The result showed that although differences were present in the gel layer thickness potentially due to differences in particle morphology, this also did not impact significantly on the dissolution process, especially in acidic and hydroalcoholic media.
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http://dx.doi.org/10.3390/pharmaceutics12090889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559722PMC
September 2020

MUCO-DIS: a New AFM-Based Nanoscale Dissolution Technique.

AAPS PharmSciTech 2020 May 17;21(5):142. Epub 2020 May 17.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK.

Mucoadhesion-based drug delivery systems have recently gained interest because of their bio-adhesion capability, which results in enhanced residence time leading to prolonged duration of action with the mucosal surface, potentially improving compliance and convenience. Mucoadhesion testing of these formulations is widely reported; however, this is technically challenging due to the absence of any standard methods and difficulty in conducting mucoadhesion, formulation-mucosal surface interaction, mucosal surface topography and drug release in a single experiment. As these measurements are currently conducted separately, on replicate formulations, results can often be subjective and difficult to correlate. Hence, the aim of the present study was to develop a new AFM-based single-entity ex vivo muco-dissolution (MUCO-DIS) technique to simultaneously evaluate mucoadhesion force, 3D surface topography, polymer dissolution and drug release characteristics. To demonstrate the potential of the current technique, the interactions between model pectin microparticles containing metformin HCl and a range of gastrointestinal mucosal surfaces (gastric, small intestine, large intestine and buccal) were studied. This novel system has not only successfully determined the mucoadhesion force, polymer dissolution and drug release information but has also highlighted the difference in microparticle performance with different mucosal targets. The current work has highlighted the potential of this newly developed MUCO-DIS system and we believe this will be a valuable tool for characterising these popular pharmaceutical formulations. This technique could also provide an opportunity to other scientific fields to evaluate materials, substrate behaviour and their interactions in their hydrated state at nanoscale with real-time chemical and surface mapping.
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http://dx.doi.org/10.1208/s12249-020-01697-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231801PMC
May 2020

Global Prevalence and Risk Factors of Gastro-oesophageal Reflux Disease (GORD): Systematic Review with Meta-analysis.

Sci Rep 2020 04 2;10(1):5814. Epub 2020 Apr 2.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, HD1 3DH, Huddersfield, UK.

Although gastro-oesophageal reflux disease (GORD) is a common medical complaint, there is currently no consensus on the global prevalence of GORD. The aim of this study was to conduct a systematic review and meta-analysis on GORD prevalence and risk factors at a global level. MEDLINE, EMBASE, CINAHL, Scopus, Cochrane library, and Google Scholar were systematically searched, without language restrictions, for studies on the prevalence and risk factors of GORD. Data were pooled using a random effects model (95% confidence interval), and the odds ratio and relative risk for each risk factor were calculated. Out of 34,355 search results, 96 records reporting the results from 102 studies fulfilled the inclusion criteria, representing 37 countries and all regions of the UN geoscheme. The global pooled prevalence of GORD was 13.98% and varied greatly according to region (12.88% in Latin America and the Caribbean to 19.55% in North America) and country (4.16% in China to 22.40% in Turkey). Using the United Nations 2017 Revision of World Population Prospects, the estimated number of individuals suffering from GORD globally is 1.03 billion. Multiple risk factors associated with a significant increase in the risk of GORD were also identified. This systematic review and meta-analysis revealed that although a substantial proportion (13.98%) of the global population suffers from GORD, there are significant variations between regions and countries. Risk factors for GORD were also identified which may allow clinicians to recognise individuals most at risk.
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http://dx.doi.org/10.1038/s41598-020-62795-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118109PMC
April 2020

Okra (Hibiscus esculentus) gum based hydrophilic matrices for controlled drug delivery applications: Estimation of percolation threshold.

Int J Biol Macromol 2020 Jul 30;155:835-845. Epub 2020 Mar 30.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, UK. Electronic address:

This study aims to explore the potential of gum extracted from okra fruit (Hibiscus esculentus) in developing hydrophilic matrices for controlled drug release applications, including determination of its percolation threshold. Flurbiprofen (poorly soluble), theophylline (sparingly soluble) and metformin (freely soluble) were employed as model drugs and incorporated using direct compression into matrices containing 40% w/w of three drugs with different physicochemical properties. Atomic force microscopy was used to study the surface texture properties of developed matrices; the surfaces of the flurbiprofen-based matrices were comparatively rough most likely as a consequence of its poor compactability. Swelling studies found that the swelling rate increased as the concentration of okra gum was increased. However, for all matrices, an increase in the gum concentration resulted in decreased drug release. The estimated percolation threshold of the okra gum calculated was found in the region of ~25% v/v plus initial porosity. Knowing the percolation threshold will enable formulators to use the minimal amount of polymer for sustain release matrices thus the controlling costs and maximising the sustainable potential of okra. This study will not only assist researchers in developing effective okra gum-based extended-release matrices but also expected to contribute towards its exploration at an industrial scale.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.03.227DOI Listing
July 2020

Thermodynamics of clay-drug complex dispersions: Isothermal titration calorimetry and high-performance liquid chromatography.

J Pharm Anal 2020 Feb 5;10(1):78-85. Epub 2019 Dec 5.

School of Applied Sciences, Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK.

An understanding of the thermodynamics of the complexation process utilized in sustaining drug release in clay matrices is of great importance. Several characterisation techniques as well as isothermal calorimetry were utilized in investigating the adsorption process of a model cationic drug (diltiazem hydrochloride, DIL) onto a pharmaceutical clay system (magnesium aluminium silicate, MAS). X-ray powder diffraction (XRPD), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and optical microscopy confirmed the successful formation of the DIL-MAS complexes. Drug quantification from the complexes demonstrated variable behaviour in the differing media used with DIL degrading to desacetyl diltiazem hydrochloride (DC-DIL) in the 2 M HCl media. Here also, the authors report for the first time two binding processes that occurred for DIL and MAS. A competitor binding model was thus proposed and the thermodynamics obtained suggested their binding processes to be enthalpy driven and entropically unfavourable. This information is of great importance for a formulator as care and consideration should be given with appropriate media selection as well as the nature of binding in complexes.
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http://dx.doi.org/10.1016/j.jpha.2019.12.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037525PMC
February 2020

Achieving gastroresistance without coating: Formulation of capsule shells from enteric polymers.

Eur J Pharm Biopharm 2019 Nov 18;144:174-179. Epub 2019 Sep 18.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, United Kingdom. Electronic address:

Capsules are a widely used oral dosage form due to their simplicity and ease of manufacture. They are equally popular for both pharmaceutical and nutraceutical products and since they do not need extensive formulation development, it is a dosage form of choice for new drugs undergoing animal or clinical trials. In addition to the standard hard-gelatin or cellulose-based vegetarian capsules, functional capsules such as those with built-in gastroresistance would be of great value. In this work, commonly used enteric polymers were investigated for the production of hard-capsules. The polymers used in this study included cellulose derivatives (HPMC AS-LF and HP-55) and acrylic/methacrylic acid derivatives (EUDRAGIT L100 and S100). A range of concentrations of polymers and plasticisers were tested to optimise the formulation for the production of capsule shells with desirable physicochemical and gastroresistance characteristics. Drug release from optimised capsules produced from HPMC AS-LF, HP-55, EUDRAGIT L100 and S100 was shown to be comparable to drug release from corresponding polymer-coated tablets in both compendial and physiological bicarbonate buffer. In summary, herein we report a simple method for producing enteric capsule shells which do not need an additional coating step which, if validated at large scale, can significantly reduce the cost of manufacturing of conventional enteric coated dosage forms. These capsules are also likely to improve the inter-tablet variability in post-gastric drug release inherent in conventional dosage forms due to coating variability.
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http://dx.doi.org/10.1016/j.ejpb.2019.09.015DOI Listing
November 2019

Using zeta potential to study the ionisation behaviour of polymers employed in modified-release dosage forms and estimating their pK.

Int J Pharm X 2019 Dec 19;1:100024. Epub 2019 Jul 19.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, United Kingdom.

A range of enteric polymers is used in pharmaceutical industry for developing gastro-resistant formulations. It is generally implied that these coatings are interchangeable due to similar dissolution pH thresholds reported by suppliers. Despite rapid dissolution in compendial phosphate buffers, these products can take up to 2 h to disintegrate in the human small intestine. The factors primarily responsible for such variability in dissolution of these polymeric coatings are the differences in ionisation of acidic functional groups on polymer chains and their interplay with ions and buffer species present in gastrointestinal fluids. In this study, we aim to develop a novel, simple and inexpensive technique that can be used under various conditions to study the ionisation behaviour of commonly used polymers (EUDRAGIT-E100, L100, S100, HPMC AS-LF, AS-HF, HP-50, HP-55) and to estimate their pK. Moreover, this method was successfully applied to study the ionisation behaviour of a range of natural polymers (Guar, Tara, locust bean, Konjac gums, gum Arabic, citrus pectin, chitosan and alginate) and their pK was also estimated. The proposed method would allow a better understanding of the dissolution behaviour of these polymers within gastrointestinal tract and will aid rational design of modified release dosage forms.
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http://dx.doi.org/10.1016/j.ijpx.2019.100024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733289PMC
December 2019

Development of a novel method utilising dissolution imaging for the measurement of swelling behaviour in hydrophilic matrices.

Int J Pharm X 2019 Dec 10;1:100013. Epub 2019 Apr 10.

Department of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, UK.

A variety of imaging techniques are currently used within the field of pharmaceutics to help understand and determine a wide range of phenomena associated with drug release from hydrophilic matrix tablets. This work for the first time aims at developing an appropriate testing imaging methodology using a surface dissolution imaging instrument (SDI2) for determining the swelling of whole compacts using hypromellose as a model hydrophilic matrix former. The influence of particle morphology (CR and DC grades) and two compressional forces (5 and 15 kN) on the initial swelling behaviour of hypromellose were investigated. The results showed that a lower absorbance of 50 mAu with a wider measurement zone proved successful in determining the edge of the gel layer and growth measurements in real-time with high level of details under flow. Despite the differences in the morphology of the grades of hypromellose tested, it was however discovered that gel growth was statistically similar between them which may be attributed to their similar chemistry. This novel method also highlighted differences in the hydrated polymer's appearance which may have been as a result of differences in porosity and solid fraction. This information is of great importance to a formulator as gel growth plays a crucial role in determining drug release from polymer compacts.
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http://dx.doi.org/10.1016/j.ijpx.2019.100013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733280PMC
December 2019

Plasticiser-Free 3D Printed Hydrophilic Matrices: Quantitative 3D Surface Texture, Mechanical, Swelling, Erosion, Drug Release and Pharmacokinetic Studies.

Polymers (Basel) 2019 Jun 28;11(7). Epub 2019 Jun 28.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK.

Hydroxypropyl methyl cellulose, HPMC, a hydrophilic polymer, is widely used for the development of extended release hydrophilic matrices and it is also considered as a good contender for the fabrication of 3D printing of matrix tablets. It is often combined with plasticisers to enable extrusion. The aim of the current project was to develop plasticizer-free 3D printed hydrophilic matrices using drug loaded filaments prepared via HME to achieve an in vitro (swelling, erosion and drug release) and in vivo (drug absorption) performance which is analogous to hydrophilic matrix tablets developed through conventional approaches. Additionally, the morphology of the printed tablets was studied using quantitative 3D surface texture studies and the porosity calculated. Filaments were produced successfully and used to produce matrix tablets with acceptable drug loading (95-105%), mechanical and surface texture properties regardless of the employed HPMC grade. The viscosity of HPMC had a discernible impact on the swelling, erosion, HPMC dissolution, drug release and pharmacokinetic findings. The highest viscosity grade (K100M) results in higher degree of swelling, decreased HPMC dissolution, low matrix erosion, decreased drug release and extended drug absorption profile. Overall, this study demonstrated that the drug loaded (glipizide) filaments and matrix tablets of medium to high viscosity grades of HPMC, without the aid of plasticisers, can be successfully prepared. Furthermore, the in vitro and in vivo studies have revealed the successful fabrication of extended release matrices.
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http://dx.doi.org/10.3390/polym11071095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680934PMC
June 2019

Effect of preparation method on the surface properties and UV imaging of indomethacin solid dispersions.

Eur J Pharm Biopharm 2019 Apr 2;137:148-163. Epub 2019 Mar 2.

Department of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, UK.

This work explores the use of UV imaging in solid dispersion systems. Solid dispersions are one of the common strategies used in improving the dissolution of poorly soluble drugs. Three manufacturing techniques (spray drying (SD), freeze drying (FD) and homogenising (HG)) are investigated. Differential Scanning Calorimetry (DSC) and X-Ray Powder Diffraction (XRPD) was used in characterising the solid dispersions. Advanced imaging was implemented to give an insight into how these solid dispersions performed. The DSC and XRPD results showed that all three methods and the various ratios studied produced amorphous solid dispersions. Ultra-Violet (UV) imaging of the pseudo Intrinsic Dissolution Rate (IDR) deduced only two samples to have superior pseudo IDR values to the IDR of the parent drug indomethacin (INDO). The whole dose imaging of the capsule formulation however showed all the samples (SD, FD and HG) to have superior dissolution to that of INDO which was in contrast to the IDR results. The UV images obtained from the determination of the pseudo IDR also showed a phenomenon the authors are reporting for the first time where increased polymer (Soluplus) content produced "web-like" strands that migrated to the top of the quartz cell which may have been responsible for the low pseudo IDR values. The authors also report for the first time using this UV imaging technique, the tip of a capsule coming off for drug to go into solution. The area under the curve suggested the best five samples dissolution wise to be 1:3 SD > 1:1 HG > 1:1 SD > 1:3 FD > 1:3 HG meaning a ratio of INDO to SOL in these dispersion of up to 1:3 being sufficient to produce significant dissolution increases. The developed interfacial (surface) area ratio (Sdr) highlighted how the surface area of the IDR compacts varied between the batches, in particular highlighting larger surface area gains for the FD and HG compacts. A choice of instrumentation/techniques to use in making solid dispersions may well come down to cost or instrument availability for a formulator as all three techniques were successful in improving the dissolution of indomethacin. This work thus highlights the importance of having both complimentary IDR and whole dosage imaging techniques in giving a better understanding of solid dispersion systems.
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http://dx.doi.org/10.1016/j.ejpb.2019.03.002DOI Listing
April 2019

Hot-melt extrusion process impact on polymer choice of glyburide solid dispersions: The effect of wettability and dissolution.

Int J Pharm 2019 Mar 27;559:245-254. Epub 2019 Jan 27.

Department of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, UK. Electronic address:

The aim of this study was to evaluate the choice of polymer and polymer level on the performance of the microstructure and wettability of hot-melt extruded solid dispersion of Glyburide (Gly) as a model drug. The produced solid dispersion were characterised using scanning electron microscopy (SEM), image analysis using a focus variation instrument (FVI), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), X-ray microtomography (XµT), dynamic contact angle measurement and dissolution analysis using biorelevant dissolution media (FASSIF). SEM and focus variation analysis showed that the microstructure and surface morphology was significantly different between samples produced. This was confirmed by further analysis using XµT which showed that an increase in polymer content brought about a decrease in the porosity of the hot-melt extruded dispersions. DSC suggested complete amorphorisation of Gly whereas XRPD suggested incomplete amorphorisation. The static and dynamic contact angle measurement correlated with the dissolution studies using FASSIF media indicating that the initial liquid imbibition process as captured by the dynamic contact angle directly affects the dissolution performance.
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http://dx.doi.org/10.1016/j.ijpharm.2019.01.038DOI Listing
March 2019

Solid lipid nanoparticles for targeted delivery of triclosan into skin for infection prevention.

J Microencapsul 2018 Nov - Dec;35(7-8):695-704. Epub 2019 Feb 20.

a Department of Pharmacy, School of Applied Sciences , University of Huddersfield , Huddersfield , UK.

Healthcare-associated infections (HAIs) are a concern for health service providers, exacerbated by poor delivery of antimicrobials to target sites within the skin. The dermal route is attractive for local and systemic delivery of drugs, however; permeation, penetration, and access to deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). Solid lipid nanoparticles present several benefits for topical delivery for therapeutic applications, especially via the follicular route. Hair follicles, surrounded by a close network of blood capillaries and dendritic cells, are an important target for delivery of antimicrobials and present a unique microbial nidus for endogenous infections in situations where the barrier is disrupted, such as after surgery, for example, triclosan, a broad-spectrum antimicrobial agent, was encapsulated into nanoparticles using glyceryl behenate and glyceryl palmitostearate (GP) solid lipids, and incorporating Transcutol P, a known permeation enhancer at different ratios. Optimised formulation was stable over 90 d and in vitro permeation studies using full thickness porcine ear skin showed that the lipid-based nanoparticles enhanced delivery of triclosan into the skin and could direct the agent towards hair follicles, indicating their potential as a carrier system for antiseptic dermal delivery.
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http://dx.doi.org/10.1080/02652048.2019.1576796DOI Listing
July 2019

Direct imaging of the dissolution of salt forms of a carboxylic acid drug.

Int J Pharm 2018 Nov 20;551(1-2):290-299. Epub 2018 Sep 20.

Department of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, UK.

The optimisation of the pharmaceutical properties of carboxylic acid drugs is often conducted by salt formation. Often, the salt with the best solubility is not chosen due to other factors such as stability, solubility, dissolution and bioavailability that are taken into consideration during the preformulation stage. This work uses advanced imaging techniques to give insights into the preformulation properties that can aid in the empirical approach often used in industry for the selection of salts. Gemfibrozil (GEM) was used as a model poorly soluble drug. Four salts of GEM were made using cyclopropylamine (CPROP), cyclobutylamine (CBUT), cyclopentylamine (CPENT) and cyclohexylamine (CHEX) as counterions. DSC, XRD and SEM were used to confirm and characterise salt formation. IDR obtained using UV-imaging up to 10 min for all the salts showed that an increase in the chain length of the counterion caused a decrease in the IDR. Past the 10 min mark, there was an increase in the IDR value for the CPROP salt, which was visualised using UV-imaging. The developed interfacial (surface) area ratio (Sdr) showed significant surface gains for the compacts. Full dosage form (capsule) imaging showed an improvement over the GEM for all the salts with an increase in chain length of the counterion bringing about a decrease in dissolution which correlated with the obtained UV-imaging IDR data.
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http://dx.doi.org/10.1016/j.ijpharm.2018.09.048DOI Listing
November 2018

Evaluating the swelling, erosion, and compaction properties of cellulose ethers.

Pharm Dev Technol 2018 Feb 29;23(2):183-197. Epub 2017 Oct 29.

a Department of Pharmacy, School of Applied Sciences , University of Huddersfield , Queensgate , Huddersfield , UK.

Swelling, erosion, deformation, and consolidation properties can affect the performance of cellulose ethers, the most commonly used matrix former in hydrophilic sustained tablet formulations. The present study was designed to comparatively evaluate the swelling, erosion, compression, compaction, and relaxation properties of the cellulose ethers in a comprehensive study using standardised conditions. The interrelationship between various compressional models and the inherent deformation and consolidation properties of the polymers on the derived swelling and erosion parameters are consolidated. The impact of swelling (K) on erosion rates (K) and the inter-relationship between Heckel and Kawakita plasticity constants was also investigated. It is evident from the findings that the increases in both substitution and polymer chain length led to higher K, but a lower K; this was also true for all particle size fractions regardless of polymer grade. Smaller particle size and high substitution levels tend to increase the relative density of the matrix but reduce porosity, yield pressure (P), Kawakita plasticity parameter (b) and elastic relaxation. Both K versus K (R = 0.949-0.980) and P versus. b correlations (R = 0.820-0.934) were reasonably linear with regards to increasing hydroxypropyl substitution and molecular size. Hence, it can be concluded that the combined knowledge of swelling and erosion kinetics in tandem with the in- and out-of-die compression findings can be used to select a specific polymer grade and further to develop and optimize formulations for oral controlled drug delivery applications.
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http://dx.doi.org/10.1080/10837450.2017.1389958DOI Listing
February 2018

Variable-focus microscopy and UV surface dissolution imaging as complementary techniques in intrinsic dissolution rate determination.

Int J Pharm 2017 Sep 22;530(1-2):139-144. Epub 2017 Jul 22.

Department of Pharmacy, University of Huddersfield, Huddersfield, HD1 3DH, UK. Electronic address:

This work reports a novel approach to the assessment of the surface properties of compacts used in Surface Dissolution Imaging (SDI). SDI is useful for determining intrinsic dissolution rate (IDR), an important parameter in early stage drug development. Surface topography, post-compaction and post-SDI run, have been measured using a non-contact, optical, three-dimensional microscope based on focus variation, the Alicona Infinite Focus Microscope, with the aim of correlating the IDRs to the surface properties. Ibuprofen (IBU) was used as a model poorly-soluble drug. DSC and XRD were used to monitor possible polymorphic changes that may have occurred post-compaction and post-SDI run. IBUs IDR decreased from 0.033mg/min/cm to 0.022mg/min/cm from 10 to 20min, respectively, during the experiment. XRD and DSC showed no form changes during the SDI run. The surface topography images showed that a distinct imprint was embossed on the surfaces of some compacts which could affect IDRs. Surface parameter values were associated with the SDI experiments which showed strong correlations with the IDR values. The variable-focus microscope can be used as a complimentary tool in the determination of IDR values from the SDI.
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http://dx.doi.org/10.1016/j.ijpharm.2017.07.053DOI Listing
September 2017

Chemical Imaging by Dissolution Analysis: Localized Kinetics of Dissolution Behavior to Provide Two-Dimensional Chemical Mapping and Tomographic Imaging on a Nanoscale.

Anal Chem 2017 06 24;89(11):5882-5890. Epub 2017 May 24.

Department of Pharmacy, School of Applied Sciences, University of Huddersfield , Queensgate, Huddersfield, HD1 3DH, United Kingdom.

A new approach to achieving chemical mapping on a nanoscale is described that can provide 2D and tomographic images of surface and near-surface structure. The method comprises dissolving material from the surface of the sample by applying a series of aliquots of solvent, then analyzing their contents after removing them; in between exposures, the surface is imaged with atomic force microscopy. This technique relies on being able to compensate for any drift between images by use of software. It was applied to a blend of two polymers, PMMA and PS. The analytical data identified the material that was dissolved, and the topography images enabled the location of the various materials to be determined by analyzing local dissolution kinetics. The prospects for generalizing the approach are discussed.
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http://dx.doi.org/10.1021/acs.analchem.7b00202DOI Listing
June 2017

Gellan gum fluid gels for topical administration of diclofenac.

Int J Pharm 2016 Dec 24;515(1-2):535-542. Epub 2016 Oct 24.

Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK; Institute of Skin Integrity and Infection Prevention, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK. Electronic address:

Diclofenac topical formulations are often preferred for drug administration to patients who experience serious GIT problems. Absorption of the drug through the skin, however, can be challenging due to the natural protective feature of the stratum corneum (SC). In this article, fluid gels prepared from gellan gum were explored as a topical drug delivery vehicle. Rheological analysis of the formulations showed that it was possible to produce a topical gel with a viscosity and the mechanical strength similar to that of the commercially available Voltaren gel using 1% w/w of a 50:50 low acyl/high acyl (LA/HA) gellan blend. Soft-tribology was used to assess the lubrication properties of gellan fluid gels. The lubrication of the gellan gum fluid gel formulations at high rubbing speeds was similar to the lubrication of the Voltaren gel. The use of gellan gum dramatically increased skin permeation of diclofenac when compared with the commercially available formulation and could be controlled by changing the gellan gum concentration and/or sodium ion concentration in the formulation. This study highlights the potential use of fluid gels that can be easily tuned to have physical properties suitable for topical formulations with the added advantage of increasing drug permeation.
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http://dx.doi.org/10.1016/j.ijpharm.2016.10.048DOI Listing
December 2016

Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions.

Colloids Surf B Biointerfaces 2016 Oct 16;146:841-51. Epub 2016 Jul 16.

Department of Pharmacy, University of Huddersfield, Huddersfield, HD1 3DH, UK. Electronic address:

This work explores the use of both spray drying and d-glucosamine HCl (GLU) as a hydrophilic carrier to improve the dissolution rate of piroxicam (PXM) whilst investigating the electrostatic charges associated with the spray drying process. Spray dried PXM:GLU solid dispersions were prepared and characterised (XRPD, DSC, SEM). Dissolution and triboelectric charging were also conducted. The results showed that the spray dried PXM alone, without GLU produced some PXM form II (DSC results) with no enhancement in solubility relative to that of the parent PXM. XRPD results also showed the spray drying process to decrease the crystallinity of GLU and solid dispersions produced. The presence of GLU improved the dissolution rate of PXM. Spray dried PXM: GLU at a ratio of 2:1 had the most improved dissolution. The spray drying process generally yielded PXM-GLU spherical particles of around 2.5μm which may have contributed to the improved dissolution. PXM showed a higher tendency for charging in comparison to the carrier GLU (-3.8 versus 0.5nC/g for untreated material and -7.5 versus 3.1nC/g for spray dried materials). Spray dried PXM and spray dried GLU demonstrated higher charge densities than untreated PXM and untreated GLU, respectively. Regardless of PXM:GLU ratio, all spray dried PXM:GLU solid dispersions showed a negligible charge density (net-CMR: 0.1-0.3nC/g). Spray drying of PXM:GLU solid dispersions can be used to produce formulation powders with practically no charge and thereby improving handling as well as dissolution behaviour of PXM.
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http://dx.doi.org/10.1016/j.colsurfb.2016.07.032DOI Listing
October 2016

Effect of mechanical denaturation on surface free energy of protein powders.

Colloids Surf B Biointerfaces 2016 Oct 5;146:700-6. Epub 2016 Jul 5.

Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UK. Electronic address:

Globular proteins are important both as therapeutic agents and excipients. However, their fragile native conformations can be denatured during pharmaceutical processing, which leads to modification of the surface energy of their powders and hence their performance. Lyophilized powders of hen egg-white lysozyme and β-galactosidase from Aspergillus oryzae were used as models to study the effects of mechanical denaturation on the surface energies of basic and acidic protein powders, respectively. Their mechanical denaturation upon milling was confirmed by the absence of their thermal unfolding transition phases and by the changes in their secondary and tertiary structures. Inverse gas chromatography detected differences between both unprocessed protein powders and the changes induced by their mechanical denaturation. The surfaces of the acidic and basic protein powders were relatively basic, however the surface acidity of β-galactosidase was higher than that of lysozyme. Also, the surface of β-galactosidase powder had a higher dispersive energy compared to lysozyme. The mechanical denaturation decreased the dispersive energy and the basicity of the surfaces of both protein powders. The amino acid composition and molecular conformation of the proteins explained the surface energy data measured by inverse gas chromatography. The biological activity of mechanically denatured protein powders can either be reversible (lysozyme) or irreversible (β-galactosidase) upon hydration. Our surface data can be exploited to understand and predict the performance of protein powders within pharmaceutical dosage forms.
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http://dx.doi.org/10.1016/j.colsurfb.2016.07.010DOI Listing
October 2016

Drug release from E chemistry hypromellose tablets using the Bio-Dis USP type III apparatus: An evaluation of the effect of systematic agitation and ionic strength.

Colloids Surf B Biointerfaces 2016 Jul 24;143:481-489. Epub 2016 Mar 24.

School of Life Sciences, University of Sussex, JMS Building, Falmer, Brighton, UK; Drug Applied Research Centre and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

The aim of the study was to evaluate the effect of systematic agitation, increasing ionic strength and gel strength on drug release from a gel-forming matrix (HPMC E10M, E4M and E50LV) using USP type III Bio-Dis apparatus with theophylline as a model drug. The triboelectric charging; particle sizing, water content, true density and SEM of all the hypromellose grades, theophylline and formulated blends were characterised. The results showed that balanced inter-particulate forces exist between drug particles and the excipient surface and this enabled optimum charge to mass ratio to be measured. Agitation and ionic strength affected drug release from E50LV and E4M tablet matrices in comparison to the E10M tablet matrices. Drug release increased substantially when water was used as the dissolution media relative to media at pH 1.2 (containing 0.4M NaCl). The results showed all f2 values for the E10M tablet matrices were above 50 suggesting the drug release from these tablet matrices to be similar. Rheological data also explained the different drug release behaviour with the stress required to yield/erode being 1Pa, 150Pa, and 320Pa, for the E50LV, E4M and E10M respectively. The stiffness of the gel was also found to be varied from 2.5Pa, 176.2Pa and 408.3Pa for the E50LV, E4M and E10M respectively. The lower G' value can be explained by a softer gel being formed after tablet introduction into the dissolution media thereby indicating faster drug release.
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http://dx.doi.org/10.1016/j.colsurfb.2016.03.066DOI Listing
July 2016