Clive G Wilson

• Ph.D.
• Professor at University of Strathclyde

Drug absorption following oral administration is determined by complex and dynamic interactions between gastrointestinal (GI) physiology, the drug, and its formulation. Since many of these interactions are not fully understood, the COST action on “Understanding Gastrointestinal Absorption-related Processes (UNGAP)” was initiated in 2017, with the a...

There have been major advances in recent years developing new sustained-release ocular drug delivery systems; however, only a small number have achieved both global regulatory approval and commercial success. Despite the challenges, there remain significant market opportunities to enhance the delivery of currently marketed, generic, or novel therap...

Treatment of ocular tissues is attempted to remedy infection, inflammatory disease and the sequelae of pathological systemic changes such as diabetes and degenerative changes associated with ageing. The anatomical features of the orbit and physiological mechanisms are important in understanding the possible limitations in drug delivery objectives a...

This collection of contributions from the European Network on Understanding Gastrointestinal Absorption-related Processes (UNGAP) community assembly aims to provide information on some of the current and newer methods employed to study the behaviour of medicines. It is the product of interactions in the immediate pre-Covid period when UNGAP members...

The delivery of drugs to the posterior segment of the eye remains a tremendously difficult task. Prolonged treatment in conventional intravitreal therapy requires injections that are administered frequently due to the rapid clearance of the drug molecules. As an alternative, intraocular implants can offer drug release for long-term therapy. However...

The absorption of oral drugs is frequently plagued by significant variability with potentially serious therapeutic consequences. The source of variability can be traced back to interindividual variability in physiology, differences in special populations (age- and disease-dependent), drug and formulation properties, or food-drug interactions. Clini...

Although oral drug delivery is the preferred administration route and has been used for centuries, modern drug discovery and development pipelines challenge conventional formulation approaches and highlight the insufficient mechanistic understanding of processes critical to oral drug absorption. This review presents the opinion of UNGAP scientists...

Cancer has been for many years the second leading cause of mortality right after cardiovascular diseases, representing 25% of all the deaths reported yearly and this tendency is expected to increase. Although the recent public health emergency caused by COVID-19 pandemic diverted much of the attention of policy makers, the public opinion and even r...

A drug delivery technology comprising a mucoadhesive bilayered buccally anchored tablet containing natamycin was developed. The concept was to anchor the tablet to the buccal tissue and allow controlled release of the drug through the matrix into the mouth. Carbomer (Carbopol ® 974 P NF) was used to formulate the mucoadhesive layer. Hydroxypropyl m...

The oral administration of solid dosage forms is the commonest method to achieve systemic therapy and relies on the drug’s solubility in human intestinal fluid (HIF), a key factor that influences bioavailability and biopharmaceutical classification. However, HIF is difficult to obtain and is known to be variable, which has led to the development of...

The European Federation of Pharmaceutical Sciences (EUFEPS) and American Association of Pharmaceutical Scientists (AAPS) have collaborated since 2015 to organize international conferences to support global harmonization of regulatory requirements for bioequivalence (BE) assessment. This collaboration has resulted in three Global Bioequivalence Harm...

It is widely recognised that drug solubility within the gastrointestinal tract (GIT) differs from values determined in a simple aqueous buffer and to circumvent this problem measurement in biorelevant fluids is determined. Biorelevant fluids are complex mixtures of components (sodium taurocholate, lecithin, sodium phosphate, sodium chloride, pancre...

The purpose of this study was to conduct an interlaboratory ring-study, with six partners (academic and industrial), investigating the measurement of intrinsic dissolution rate (IDR) using surface dissolution imaging (SDI) equipment. Measurement of IDR is important in pharmaceutical research as it provides characterising information on drugs and th...

In theory, introducing a drug directly into the eye should localise drug effects permitting efficient exchange of the drug between the vehicle and the cornea. Moreover since the blood supply to the eye represent such a small proportion of the output of the heart, the bystander effects should be greatly reduced by confining the dose, and other unwan...

The general target for a typical ophthalmic topical medication is a 2‐year shelf life before opening, and a storage time of 28 days at room temperature on initiation of use. Topically applied drugs and excipients will disrupt the tear film and alter vision until normal refraction is achieved by blinking. The space for delivery differs between the t...

Ocular drug delivery offers unique challenges and opportunities in the era of novel therapeutic agents ranging from small molecules to gene therapies. Noninvasive delivery of drugs into the back of the eye or any part of the eye is extremely limited by short precorneal residence time and formidable biological barriers. The eye is a sensitive, senso...

Oral administration is the most common route of drug delivery. The absorption of a drug from the gut into the bloodstream involves disintegration of the solid dosage form, dissolution of the active pharmaceutical ingredient and its transport across the gut wall. The efficiency of these processes is determined by highly complex and dynamic interplay...

Oral administration of a solid dosage form requires drug dissolution in the gastro-intestinal tract before absorption. Solubility is a key factor controlling dissolution and it is recognised that within the intestinal tract this is influenced by the luminal fluid pH, amphiphile content and composition. Various simulated intestinal fluid recipes hav...

The evaluation of biological responses to polymeric scaffolds are important, given that the ideal scaffold should be biocompatible, biodegradable, promote cell adhesion and aid cell proliferation. The primary goal of this research was to measure the biological responses of cells against various polymeric and collagen electrospun scaffolds (polycapr...

Silk is a remarkable biopolymer with a long history of medical use. Silk fabrications have a robust track record for load-bearing applications, including surgical threads and meshes, which are clinically approved for use in humans. The progression of top-down and bottom-up engineering approaches using silk as the basis of a drug delivery or cell-lo...

This chapter discusses the concept of user-friendly medicine and its importance in dosage forms. The oral route remains the mainstay of methods of dosing with medicines on the grounds of cost, convenience and public familiarity. Although alternative routes, for example skin and lung, exploiting developments in drug delivery technology have become p...

The oral route is the preferred option for drug administration but contains the inherent issue of drug absorption from the gastro-intestinal tract (GIT) in order to elicit systemic activity. A pre-requisite for absorption is drug dissolution, which is dependent upon drug solubility in the variable milieu of GIT fluid, with poorly soluble drugs pres...

Upon oral administration the solubility of a drug in intestinal fluid is a key property influencing bioavailability. It is also recognised that simple aqueous solubility does not reflect intestinal solubility and to optimise in vitro investigations simulated intestinal media systems have been developed. Simulated intestinal media which can mimic ei...

For the creation of scaffolds in tissue engineering applications, it is essential to control the physical morphology of fibres and to choose compositions which do not disturb normal physiological function. Collagen, the most abundant protein in the human body, is a well-established biopolymer used in electrospinning compositions. It shows high in-v...

The absorption of poorly water-soluble drugs is influenced by the luminal gastrointestinal fluid content and composition which controls solubility. Simulated intestinal fluids have been introduced into dissolution testing including endogenous amphiphiles and digested lipids at physiological levels; however, in vivo individual variation exists in th...

It's Just Mucosa - Get Over It, By Prof. Clive Wilson, The barriers to drug absorption at sites of dosage form application vary enormously around the body. The need to maintain a homeostatic environment and the vulnerability of organs to toxins necessitate isolation from the exterior world by epithelial barriers. These epithelial barriers perform m...

The chemical distribution and mechanical effects of drug compounds in loaded electrospun scaffolds, a potential material for hernia repair mesh, were characterised and the efficacy of the material was evaluated. Polycaprolactone electrospun fibres were loaded with either the antibacterial agent, irgasan, or the broad-spectrum antibiotic, levofloxac...

Gastrointestinal fluid is a complex milieu and it is recognised that gut drug solubility is different to that observed in simple aqueous buffers. Simulated gastrointestinal media have been developed covering fasted and fed states to facilitate in vitro prediction of gut solubility and product dissolution. However, the combination of bile salts, pho...

Various gastrointestinal (GI) factors affect drug and formulation behavior after oral administration, including GI transfer, motility, pH and GI fluid volume and composition. An in-depth understanding of these physiological and anatomical variables is critical for a continued progress in oral drug development. In this review, different methodologie...

Gastrointestinal drug administration is the preferred route for the majority of drugs however, the natural physiology and physicochemistry of the gastrointestinal tract is critical to absorption but complex and influenced by factors such as diet or disease. The pharmaceutical sciences drive for product consistency has led to the development of in v...

Ultrafast lasers offer a possibility of removing soft ophthalmic tissue without introducing collateral damage at the ablation site or in the surrounding tissue. The potential for using ultrashort pico- and femtosecond pulse lasers for modification of ophthalmic tissue has been reported elsewhere and has resulted in the introduction of new, minimall...

A scalable platform to prepare multi-functional ocular lenses is demonstrated. Using rapidly dissolving polyvinylpyrrolidone (PVP) as the active stabilizing matrix, both sides of ocular lenses were coated using a modified scaled-up masking electrohydrodynamic atomization (EHDA) technique (flow rates variable between 5 and 10 µL/min, applied voltage...

A drug's solubility and dissolution behaviour within the gastrointestinal tract is a key property for successful administration by the oral route and one of the key factors in the biopharmaceutics classification system. This property can be determined by investigating drug solubility in human intestinal fluid (HIF) but this is difficult to obtain a...

Drug delivery into the nasal cavity has an established role in local delivery of over-the-counter medicines used to treat allergic rhinitis and blocked sinuses. Whilst older dosage forms (such as nasal bougies) have fallen from favour over the years, nasal sprays and nasal drops remain the staple dosage forms for drug delivery into the nasal cavity...

This review summarizes the current knowledge on anatomy and physiology of the human gastrointestinal tract in comparison with that of common laboratory animals (dog, pig, rat and mouse) with emphasis on in vivo methods for testing and prediction of oral dosage form performance. A wide range of factors and methods are considered in addition, such as...

We demonstrate that an optically trapped silica bead can be used as a local probe to measure the micro-rheology of the vitreous humor. The Brownian motion of the bead was observed using a fast camera and the micro-rheology determined by analysis of the time-dependent mean-square displacement of the bead. We observed regions of the vitreous that sho...

OrBiTo is a new European project within the IMI programme in the area of oral biopharmaceutics tools that includes world leading scientists from nine European universities, one regulatory agency, one non-profit research organisation, four SMEs together with scientists from twelve pharmaceutical companies. The OrBiTo project will address key gaps in...

A systematic study was undertaken to gain more insight into the mechanism of transdermal delivery of nanoencapsulated model dyes across microneedle (MN)-treated skin, a complex process not yet explored. Rhodamine B (Rh B) and fluorescein isothiocyanate (FITC) as model hydrophilic and hydrophobic small/medium size molecules respectively were encapsu...

Abstract The vitreous humor represents a significant barrier to the penetration of nanoparticulate-based ocular drug delivery systems. The gel structure and biochemical components of the vitreous will impact on the rate of nanoparticle movement through the tissue to reach the retinal tissue. As well as structure of the vitreous, flow systems operat...

As to the alignment of "Horizon 2020", ir is a more integrated approach to European science policy than expressed in the proposals previously drafted, and specifically considers: (i) promoting excellence in Science, (ii) establishing a sound industrial leadership and (iii) expressing an ambition to address current and future societal challenges. In...

Drug flux across microneedle (MN)-treated skin is influenced by the characteristics of the MN array, formed microconduits and physicochemical properties of the drug molecules in addition to the overall diffusional resistance of microconduits and viable tissue. Relative implication of these factors has not been fully explored. In the present study,...

There is an urgent need to replace the injection currently used for low molecular weight heparin (LMWH) multidose therapy with a non- or minimally invasive delivery approach. In this study, laser-engineered dissolving microneedle (DMN) arrays fabricated from aqueous blends of 15% w/w poly(methylvinylether-co-maleic anhydride) were used for the firs...

We characterized differences in biochemical composition of the vitreous of different animal species with respect to small molecule constituents. Vitreous samples were extracted from sheep, pig, Dutch Belted rabbits, and New Zealand white rabbits. The vitreous samples were investigated for acetylcholinesterase (AChE) activity and, in addition, were...

Gastrointestinal side-effects of alendronate (ALN) are believed to be associated with oesophageal lodging of tablets and perhaps reflux of gastric contents with alendronate under strongly acidic pH conditions. This leads to unfavourable posture restrictions when dosing. This clinical study evaluated gastric emptying and gastric pH after administrat...

This book provides a critical overview of the advances being made towards overcoming biological barriers through the contribution of nanosciences and nanotechnologies. Overcoming these barriers is of primary importance for solving the problems of many current drugs and vaccines and it is also especially relevant for the commercial exploitation of n...

Disease processes and ageing require therapeutic intervention to ameliorate or eliminate, when possible, the effects of pathologies on everyday living. Ageing is associated with a gradual degeneration and subsequent alteration of the balance of the body’s control systems. Drugs are useful therapeutic agents that interact with cellular targets to pr...

Ravimite uurimistöös on viimase paarikümne aastaga sünteesitud hulgaliselt uusi toimeainete kandidaatmolekule, mille toime on varasematest oluliselt tõhusam, kuid millest on siiski keeruline toota suu kaudu manustatavaid ravimivorme. Niisuguste uute ravimpreparaatide arendamise teeb iseäranis keeruliseks asjaolu, et lisaks suukaudsetele ravimivormi...

The treatment of posterior eye diseases, such as diabetic retinopathy and age-related macular degeneration, is of growing interest as the number of people affected by these conditions continues to rise. This study utilises the methods of cassette dosing and the perfused ovine eye model - to reduce animal usage and therefore animal time - to show th...

Nadroparin calcium (NC), a low molecular weight heparin (4.4 kD), is administered by subcutaneous injection because of poor oral absorption and skin penetration [1]. Microneedle (MN) penetration has been shown to enhance transdermal delivery of various drugs by puncturing the stratum corneum [2]. Dissolving microneedles (DMNs) offer an additional a...

To illustrate the ability of time-of-flight secondary ion mass spectrometry (ToF-SIMS) to characterize and demonstrate the spatial distribution of dexamethasone within ocular tissues. Dexamethasone sodium phosphate was administrated to perfused and nonperfused ovine eyes via intravitreal injections. The vitreous humor, the lens, and the retina of t...

Oral drug delivery remains the mainstay of patient treatment although the candidate drugs of the new millennium are becoming increasingly difficult to formulate for good systemic absorption. The area of oral delivery therefore represents an important area of innovation for pharmaceutical formulation including modulating solubility, exploiting windo...

We present results demonstrating for the first time that an optically trapped bead can be used as a local probe to measure the variation in the viscoelastic properties of the vitreous humor of a rabbit eye. The Brownian motion of the optically trapped bead was monitored on a fast CCD camera on the millisecond timescale. Analysis of the bead traject...

In recent years, vitreous humour, a connective tissue at the centre of the eye, emerged as a preferred reservoir for back of the eye drug delivery. Although vitreous humour is largely composed of water (>99%), its physical form can range from a firm gel in the youth to a collapsed gel in the elderly. These changes in the physical form of the vitreo...

An essential basis for the understanding of the complex interplay between oral drug delivery systems and gastrointestinal physiology is the ability to relate deposition of the dosage form to the plasma concentration time profile. The pharmaceutical scientist requires an array of methods that provide information on formulation disposition without in...

Acetaminophen (paracetamol, APAP) is widely used to relieve mild-to-moderate pain and reduce fever. Absorption of the drug can be impacted by dosage form; this may have implications for pain relief in some individuals, potentially accounting for suboptimal efficacy in analgesia. To assess the disintegration and dissolution of a new fast-dissolving...

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to obtain mass spectra from three ocular tissues, the lens, the vitreous and the retina. All three tissues were extracted from control ovine eyes and ovine eyes treated with model drug. To identify variations in surface biochemistry of each ocular tissue, principal component analysi...

The distribution of 131 I-labelled liposomes with sodium iodide entrapped in the aqueous core has been compared with that of a preparation containing iodinated phospholipid, following i.v. administration to rabbits. Liver uptake was observed initially with both liposomes, but the distribution of the former preparation soon became indistinguishable...

The effect of the inclusion of aluminium hydroxide on the neutralization profiles and raft strength of alginate-based antacid formulations was investigated using in vitro techniques. The results indicate that the aluminium hydroxide remains associated with the raft material and does not neutralize the acid layer below. The physical strength of the...

Introduction: A dual microneedles (MN) /PLGA nanoparticles (NPs) approach was reported earlier to result in marked enhancement in skin permeation of rhodamine B (Rh B) dye through full thickness pig skin [1]. The objective of this study was to gain more insight into the enhancement mechanism by investigating the effect of PLGA NPs characteristics o...

Introduction: Microneedle arrays (MN) have been extensively investigated as a new technology permitting skin penetration of a wide variety of small drugs and macromolecules [1]. The mechanism of MN-mediated permeation enhancement has not been fully elucidated. Our aim was to assess the influence of the permeant physicochemical properties on MN-assi...

Peptidases in the lung are well placed to have an important role in regulating levels of circulating endogenous and therapeutic peptides. They also present a first-pass metabolic barrier for peptides delivered to the lung for systemic absorption. The activities of five peptidases were surveyed in the pulmonary circulation of the asanguinous isolate...

The goal of the present work was to develop a swellable hydrogel colonic delivery system, which would maximise the availability of the therapeutic agent at a site of inflammation, especially where the water is scarce. A novel method was developed to manufacture a biodegradable and reversible polyelectrolyte complex (PEC) containing chitosan and pol...

Controlling the rate, extent and time of a drug’s delivery can optimize its performance in many ways, relative to “immediate release” delivery. Such optimized design requires a broad knowledge base of topics such as gastro intestinal tract physiology, polymer science, and the mechanisms by which drugs are released from the formulated units. Technol...

The basic science part of this article focuses on the anatomic barriers to the five major modes of ocular drug delivery: intraocular, periocular, hybrid, topical, and systemic. The second half is a review of the clinical and regulatory components of translational science.

The effects of vitreous liquefaction in the elderly on the distribution of drugs from intravitreal injections, depots, or devices remains unclear. The purpose of the present study was to develop a liquefied vitreous model that simulates the aged condition, to enable the study of clinically relevant drug distribution. Dutch-belted rabbits were used...

Colonic transit is a subject of great relevance when considering in vivo/in vitro relationships for oral controlled release dosage forms. Our knowledge of colonic motility has first come from the clinic, where measurement of the whole gut transit of different excreted markers was used as a method of discriminating pathologies. X-ray contrast, altho...

To assess the feasibility of using two-photon microscopy to study the pattern of diffusion through the sclera of a tracer (tazarotenic acid [TA]). Polyvinyl alcohol films containing 1% tazarotenic acid (PVA-TA) were applied to the equatorial sclera of isolated perfused bovine eyes. Two-photon microscopy (TPM) was used to determine the lateral sprea...

This article aims to provide an interpretation and perspective on current concepts and recent literature regarding the evidence for individualizing intravitreal therapy (IVT), particularly considering iatrogenic and patient factors in the management of neovascular age-related macular degeneration (AMD). As ocular parameters that govern IVT pharmaco...

We report on the development of a novel, low cost instrument that is capable of accurately measuring small, short and long term changes in the thickness of the cornea and tear film at high speed. The performance of the instrument was tested by measuring the influence of Allergan's OPTIVETM lubricating eye drops on the thickness of the cornea and te...

The ocular structures are very sensitive to damage from ultraviolet (UV) radiation, exposure is linked to corneal and conjunctival damage, cataract formation and may also be implicated in the aetiology of age-related macular degeneration. These structures are usually protected by wearing suitable eyeglasses and goggles. An alternative to convention...

IntroductionThe TargetsThe Upper GI Tract: Mouth and EsophagusMid-GI Tract: Stomach and IntestineThe Lower GI Tract: The ColonPathophysiological Effects on TransitPathophysiological Effects on PermeabilitypHConclusions References

Three time-delayed capsule (TDC) formulations were investigated in a pharmacoscintigraphic study, using a three-way crossover design in eight healthy male volunteers. Additionally, the pulsed release of a TDC was investigated with time-lapse photography, using a nondisintegrating riboflavin tablet. The photographic study indicated how the release c...

The selective EGFR tyrosine kinase inhibitor, gefitinib has been shown to be active against certain human carcinomas. It had been noted that a proportion of volunteers consistently had lower gefitinib exposure following oral administration. The shape of the elimination profile in this subset was also different, showing a monophasic elimination patt...

IntroductionOverviewEgalet TechnologyEgalet Matrix ErosionManufactureClinical ExperienceFuture WorkConclusion References

The in vivo evaluation of colon-targeting tablets was conducted in six healthy male volunteers. A pectin-hydroxypropyl methylcellulose coating was compressed onto core tablets labelled with 4MBq (99m)Tc-DTPA. The tablets released in the colon in all subjects; three in the ascending colon (AC) and three in the transverse colon (TC). Tablets that rel...

To validate Magnetic Moment Imaging (MMI) for the investigation of gastrointestinal transit and disintegration of solid dosage forms and to correlate the MMI findings with the corresponding gamma scintigraphic data. Three magnetic tablets (MTs) were investigated using in vitro and in vivo tests. The clinical study was a four-way, crossover study wi...

The prediction of the in vivo drug release characteristics of modified release oral dosage forms by in vitro dissolution tests is a prerequisite for successful product development. A novel dissolution test apparatus that mimics the physical conditions experienced by an oral formulation during gastrointestinal transit was developed. This included th...

Surface-enhanced Raman scattering (SERS) is shown to give linear and sensitive concentration-dependent detection of folic acid using silver nanoparticles created via ethylene-diaminetetraacetic acid (EDTA) reduction. Optical detection by SERS overcomes the primary limitation of photodissociation encountered during the application of other shorter w...

Conventional controlled-release products for oral administration normally lack any unique property which would facilitate drug targeting to a specific location in the gastrointestinal tract. In view of the time course of gastrointestinal transit, any slow release system having a drug release-time profile extending beyond 6 to 8 hours is likely to b...

The market for controlled and sustained release delivery forms is well established. Apart form the obvious applications for drugs with short halflives and narrow therapeutic windows, sophisticated delivery systems open up the path for development of drugs with less than ideal physicochemical properties and allow better treatment of diseases which d...

The most extensive application of a formulation strategy for colonic delivery and generally for controlled release has been the employment of enteric coatings on solid substrates. This is a natural development of conventional coating technologies employed to avoid gastric release thus preventing stability problems such as degradation, or unwanted p...

Targeted delivery of drugs to the colon has been employed to achieve one or more of four objectives. The desired outcomes can be (i) sustained delivery to reduce dosing frequency; (ii) to delay delivery to the colon to achieve high local concentrations in the treatment of diseases of the distal gut; (iii) to delay delivery to a time appropriate to...

In many therapeutic applications it would be advantageous to deliver orally-administered drug into the systemic circulation some time after swallowing the formulation. Examples include the treatment of nocturnal asthma and prevention of secondary serious arrhythmias provoked by postural changes following previous severe cardiac ischemia. Many physi...

Food stimulates changes to gastrointestinal secretion and motility patterns, however, the effect of smaller quantities of lipid, such as that contained in a lipid-based drug formulation, has not been detailed. This study aimed to examine the effects of small quantities of lipid on gastric emptying and biliary secretion. The influence of oral admini...

Bioadhesive dosage forms are a potential method for overcoming rapid mucociliary transport in the nose. A lyophilised nasal insert formulation previously investigated in sheep demonstrated prolonged absorption of nicotine hydrogen tartrate suggestive of extended nasal residence, and increased bioavailability. The current study was performed to quan...

Eyesight is unquestionably the most important modality of perception that humans possess. It is so central to our way of life that irrational fear of losing vision, termed Scoptophobia or Scotomaphobia, is totally incapacitating for some individuals. Creationists suggested that an organ as special as the human eye could not have come about by chanc...

To develop an improved ((1)This is to clearly acknowledge that we have tried to improve an existing model.) arterially perfused bovine eye model and investigate the general ocular disposition of memantine. Fresh bovine eyes were prepared by exposing and cannulating one ciliary artery, placing the eye into a perfusion chamber and slowly increasing t...

Amphiphilic chitosan-based polymers (Mw < 20 kDa) self-assemble in aqueous media at low micromolar concentrations to give previously unknown micellar clusters of 100-300 nm in size. Micellar clusters comprise smaller 10-30 nm aggregates, and the nanopolarity/drug incorporation efficiency of their hydrophobic domains can be tailored by varying the d...

To highlight key factors of a clinical protocol design that can impact evaluation of gastroretentive dosage forms. Also, to provide a preferred clinical protocol design to allow potential standardization of clinical evaluation and direct comparisons of inventions.

Buccal bioadhesive tablet formulations of nicotine hydrogen tartrate (NHT) for nicotine replacement therapy (NRT) were developed using chitosan and carbomer at different ratios. Magnesium hydroxide was incorporated into the formulations as pH increasing agent. In vitro release and bioadhesion properties of the tablets were investigated. Release of...