Brian William Barry

University of Bradford | UB

Abstract Dermatological preparations may be formulated for optimal bioavailability by ensuring that the drug has maximum tendency to leave the vehicle and pass into the skin. Alternatively, compounds (penetration enhancers, accelerants, or sorption promoters) may be included in the formulation that themselves pass into the skin and in so doing reve...

Abstract The barrier function of human skin may be disrupted by anionic surfactants. Any agent that can prevent such action may be of benefit. This investigation was designed to examine the protective activity of poly-oxyethylated nonionic surfactants against the harmful effects of divalent anionic surfactants on human skin. Permeation studies were...

The vasoconstrictor assay for topical steroids has been modified and extended so that it may be used to screen for activity and to determine bioavailability. The precision, sensitivity and reproducibility were good for a bioassay. Hydro-philic preparations containing steroid in solution exhibited rank-order relationships between applied concentrati...

The early eighties saw the introduction of liposomes as skin drug delivery systems, initially promoted primarily for localised effects with minimal systemic delivery. Subsequently, a novel ultradeformable vesicular system (termed “Transfersomes” by the inventors) was reported for transdermal delivery with an efficiency similar to subcutaneous injec...

Maintaining protein conformational stability and integrity during formulation is critical for developing protein pharmaceuticals. Accordingly, high sensitivity differential scanning calorimetry (HSDSC) and Fourier transform (FT)-Raman spectroscopy were employed to assess conformational stabilities (thermal stability and folding reversibility) and s...

The production of stable protein formulations is difficult due to unique properties of proteins. Accordingly, spray drying and crystallisation techniques were assessed for their effects on trypsin, a model protein. Samples were investigated using polarising microscopy, thermogravimetry, differential scanning calorimetry (DSC), FT-Raman spectroscopy...

Abstract Various aspects of soft paraffins, with the main emphasis on their rheological properties, are considered in a review of 119 references. Rheological test methods currently used are critically appraised in sections on penetrometry, continuous shear viscometry, oscillatory testing and creep analysis. The chemical nature, microscopic structur...

Spreadability characteristics of official creams and ointments of the British Pharmacopoeia and the British Pharmaceutical Codex were determined using the Master Curve concept and continuous shear data. Experimental results were obtained using a Ferranti-Shirley cone and plate viscometer at 25 d̀C and 34 d̀C, representing an approximate temperature...

A coherent explanation is presented of the mechanisms by which mixed emulsifiers of the surfactant/fatty alcohol type both stabilise and control the consistencies of oil-in-water emulsions. Original and published data are used to develop a theory in which the semisolid and other flow properties of emulsions are related to the nature, strength and e...

Among the myriad strategies employed to increase both the amount of a therapeutic agent traversing the skin and the range of drugs that can be effectively delivered through this route, lies in the application of chemical penetration enhancers. These agents interact with stratum corneum constituents to promote drug flux. Such materials have been use...

As the human skin is the largest single organ of the body, it may at first sight be attractive to formulators as an accessible means of drug input. This route of delivery holds many advantages that include avoidance of GI and liver first pass effects, controlled and continuous drug delivery, easy removal of the dosage form, and good patient complia...

Electroporation can be defined as an electrical enhancement strategy whereby relatively high voltages are applied to the skin for very brief periods in order to create temporarily aqueous pores within the membrane. These apertures provide pathways for molecular penetration through the skin. Its potential for increasing the transdermal delivery of m...

Background/aims Raman spectroscopy has been used for a range of biomedical applications: the study of normal and diseased tissues, and the interaction of chemical agents with tissues, implants and even single cells. The object here was to review the extent to which the Raman spectroscopic technique has been applied to skin research, considering the...

Using liposomes to deliver drugs to and through human skin is controversial, as their function varies with type and composition. Thus they may act as drug carriers controlling release of the medicinal agent. Alternatively, they may provide a localized depot in the skin so minimizing systemic effects or can be used for targeting delivery to skin app...

Penetration enhancers are chemicals that temporarily and reversibly diminish the barrier function of the outermost layer of skin, the stratum corneum, to facilitate drug delivery to and through the tissue. In the current study, the complex mechanisms by which 1,8-cineole, a potent terpene penetration enhancer, disrupts the stratum corneum barrier i...

Historically, the skin was believed to have evolved as a control barrier to the outward transport ofwater and the inward movement of topically contacting agents [1, 2]. In contrast to this evolutionary standpoint, over the last three decades, the use of intact skin as a potential site for local and continuous systemic administration of drugs has re...

An important step in liposome characterization is to determine the location of a drug within the liposome. This work thus investigated the interaction of dipalmitoylphosphatidylcholine liposomes with drugs of varied water solubility, polar surface area (PSA) and partition coefficient using high sensitivity differential scanning calorimetry. Lipophi...

The outermost layer of the skin (stratum corneum) provides the principal barrier to permeation and consists of corneocytes embedded in a highly organized lipid matrixMany techniques have been developed to overcome the barrier. This chapter summarizes our present knowledge of means by which lipid vesicles under iontophoresis, electroporation, and co...

Moisture and temperature promote protein degradation. The stabilities of commercial, crystallised and spray-dried lysozyme, a model protein, were assessed under these stresses to explore whether a crystalline protein had better storage stability than a conventionally produced one. Samples were maintained at different relative humidities (RH) and te...

Incorporating edge activators (surfactants) into liposomes was shown previously to improve estradiol vesicular skin delivery; this phenomenon was concentration dependent with low or high concentrations being less effective. Replacing surfactants with limonene produced similar behaviour, but oleic acid effects were linear with concentration up to 16...

This work investigated transdermal penetration of a model lipophilic drug (estradiol) through human epidermis from phosphatidylcholine (PC)-based liposomes and saturated aqueous estradiol solution (control). Representative examples of cholate-containing ultradeformable (Transfersomes), non-rigid (pure PC) and membrane-stabilized (cholesterol-contai...

One long-standing approach for improving transdermal drug delivery uses penetration enhancers (also called sorption promoters or accelerants) which penetrate into skin to reversibly decrease the barrier resistance. Numerous compounds have been evaluated for penetration enhancing activity, including sulphoxides (such as dimethylsulphoxide, DMSO), Az...

The solubility of penciclovir (C(10)N(5)O(3)H(17)) in a novel film formulation designed for the treatment of cold sores was determined using X-ray, thermal, microscopic and release rate techniques. Solubilities of 0.15-0.23, 0.44, 0.53 and 0.42% (w/w) resulted for each procedure. Linear calibration lines were achieved for experimentally and theoret...

A novel approach for identifying synergistic mixtures of skin penetration enhancers promises to transform development of transdermal products, including patches.

This work investigated the effect of electroporation on human epidermal penetration of a model neutral lipophilic compound (estradiol) from saturated aqueous solution and when encapsulated in ultradeformable liposomes. Total amount penetrated and skin deposition were compared with values obtained from passive diffusion. The effect of electrical pul...

The study was conducted to investigate the possible combination between electroporation and ultradeformable liposomes to enhance the transdermal penetration of estradiol. The unexpected reduced drug permeation after combined electroporation and liposomes compared to control aqueous drug solution would indicate that liposomal phosphatidylcholine app...

This work explored the role of skin appendages (shunt route) in passive and iontophoretic drug and liposome penetration. The technique used an epidermis and stratum corneum sandwich from the same skin donor with the additional stratum corneum forming the top layer of the sandwich. Penetration was monitored during occluded passive and iontophoretic...

The role of hair follicles in transdermal delivery remains difficult to elucidate due partly to animal model complications. This paper explores a novel technique employing two human skin membranes to differentiate shunt route delivery from bulk transepidermal input. The method monitors penetration through epidermal membranes and compares this with...

The development of proteins as therapeutic agents is challenging partly due to their inherent instabilities. Consequently, crystallisation and spray drying techniques were assessed to determine their effects on protein integrity using lysozyme as a model protein. Unprocessed, crystallised and spray-dried lysozyme were characterised by: thermal anal...

The stratum corneum (SC) barrier typically consists of layers of corneocytes embedded in a lipid continuum that regulates barrier function. The lipid domain containing ceramides, cholesterol, and free fatty acids provides the major pathway for most drugs permeating across SC. Penetration enhancers diminish the SC barrier function. The classic enha...

This work evaluated the in vitro transdermal iontophoretic delivery of tritiated estradiol from ultradeformable liposomes compared with saturated aqueous solution (control). Effects of current density and application time on tritium exchange with water were also determined. Penetration studies used three Protocols. Protocol I involved occluded pass...

Human skin delivery of estradiol from ultradeformable and traditional liposomes was explored, comparing occlusive and open application, with the aim of examining the role of skin hydration. Partially hydrated epidermis was used for open hydration, but fully hydrated membranes were used for occluded studies. In addition, we developed a novel techniq...

The effect of melting point of chiral penetration enhancers on their stratum corneum uptake was investigated. The pure enantiomers of a chiral compound often possess different melting points, and therefore dissimilar solubilities, to the racemate because of variations in their crystal structure. Two terpenes, menthol and neomenthol, saturated in pr...

When measured by the number of medicines consumed or prescriptions written, the topical and transdermal routes of drug delivery pale into insignificance compared with oral therapy. Industrial colleagues, therefore, occasionally adopt a somewhat utilitarian stance and question the value of academic research into skin treatment and drug permeation, w...

Optimisation of drug delivery through human skin is important in modern therapy. This review considers drug-vehicle interactions (drug or prodrug selection, chemical potential control, ion pairs, coacervates and eutectic systems) and the role of vesicles and particles (liposomes, transfersomes, ethosomes, niosomes). We can modify the stratum corneu...

The potential use of ultradeformable and standard liposomes as skin drug delivery systems was investigated in-vitro. An improved experimental design gave a good measure for skin deposition of drug. This avoided the contamination that can occur due to incomplete washing of the donor before direct determination of the amount of drug in the skin. The...

Transdermal permeation of propranolol through human skin in the presence of fatty acid (lauric, capric) penetration enhancers has been investigated. Thermal analysis showed that binary mixtures of propranolol with either fatty acid were not simple mechanical mixtures of the two components. Propranolol formed 1:1 molar addition compounds with both l...

The aim of this study was to investigate the importance of liposome structure in oestradiol skin delivery as a tool for understanding the delivery mechanism from lipid vesicles. Liposomes of phosphatidylcholine (PC) (1), PC, sodium cholate; 86:14 w/w (II), PC, Span 80; 86.7:13.3 w/w (III) and PC, oleic acid: 84:16 w/w (IV) with 1 mg/ml radiolabelle...

The aims of this study were to refine ultradeformable liposomes for oestradiol skin delivery and to evaluate Span 80 and Tween 80 as edge activators compared with sodium cholate. Vesicles containing phosphatidylcholine (PC) mixed with edge activators and oestradiol were prepared. Entrapment efficiency and vesicle size were determined. Interactions...

Deformable vesicles and traditional liposomes were compared as delivery systems for oestradiol to elucidate possible mechanisms of drug delivery through human skin. Accordingly, epidermal permeation of oestradiol from optimized deformable vesicles and traditional liposome formulations was studied under low dose non-occluded conditions. Five mechani...

The resurgence of Raman spectroscopy, in the late 1980's has led to an increase in the use of the technique for the analysis of biological tissues. Consequently, Raman spectroscopy is now regarded to be a well-established non- invasive, non-destructive technique, which is used to obtain good quality spectra from biological tissues with minimal fluo...

FT-Raman spectroscopy has been used as a tool for investigating permeation into and diffusion through human skin membranes. Thermal studies showed that the lipid component of stratum corneum, the outermost layer of skin and the main barrier to diffusion of most drugs, is disrupted as the lipids melt. This measure for disruption provides a positive...

'It is better to be approximately right rather than precisely wrong.'

5-Fluorouracil permeates the stratum corneum through the intercellular pathway. 5-Fluorouracil is hydrophilic and, therefore, its partitioning from the aqueous region into the hydrocarbon interior of stratum corneum lipids is expected to be an important stage of its permeation and a target for some permeation enhancers. It has also been reported th...

The purpose of this study was to investigate permeation modulation by beta- and 2-hydroxypropyl-beta-cyclodextrins (beta-CD and HP-beta-CD, respectively) alone and complexed with penetration enhancers for the test drugs 5-fluorouracil and estradiol through human skin, and to probe the value of the CDs in a barrier cream against toluene exposure. Me...

Thermal transitions in desiccated stratum corneum membranes of neonatal rats, mice and rabbits and adult abdominal human skin were investigated using differential scanning calorimetry (DSC). Four endothermic transitions at 39–45 (T1), 55–58 (Tx), 68–74 (T2) and 77–86°C (T3) were observed. T1, T2 and T3 were attributed to phase changes in the interc...

FT-Raman spectra have been recorded from human stratum corneum in vivo and in vitro using a fibre optic coupling. Spectra from both tissues were near identical illustrating the validity of in vitro studies for examining the mechanisms of action of penetration enhancers in vivo. Treatment of excised human skin with the penetration enhancer 1,8-cineo...

The molecular basis of lipid packing in human stratum corneum and a model phospholipid system has been studied as a function of temperature using Fourier Transform (FT) Raman spectroscopy. Thermally induced molecular rearrangements of the model lipid system, dipalmitoylphosphatidyl choline (DPPC), and stratum corneum were investigated using FT Rama...

Healthy and abnormal human skin has been examined using Fourier transform (FT) Raman spectroscopy. The molecular basis of alternations in this tissue have been proved with the aim of providing a tool to aid in clinical diagnosis of skin disorders. Intact human stratum corneum show spectral features of keratin and the lipids. Spectra from callus and...

FT-Raman spectroscopy has been used to investigate treated verrucae (warts from the sole of the foot) with a local application of a salicylic acid paint. Differences in the molecular structure of the stratum corneum across the verruca sample were observed, and by comparison with normal and hyperkeratotic skin it was concluded that the tissue around...

The formation of eutectic systems between ibuprofen (ibu) and seven terpene skin penetration enhancers was studied and, by using the eutectic systems as donors, the effects of melting point depression of the delivery system on transdermal delivery were investigated. A range of ibu:terpene binary mixtures were melted together, cooled, and recrystall...

Raman spectroscopy has been used in a variety of biomedical applications including normal and diseased human tissues, single cells, implants and the presence of foreign inclusions following implantation and the interaction of certain chemical agents with tissues. This paper surveys recent advances in biomedical Raman spectroscopy. © 1997 by John Wi...

The principal barrier to transdermal delivery of most drugs is the lamellar intercellular lipid domain of the stratum corneum (SC). Previously, we reported a lamellar matrix capable of modelling the structural and barrier properties of the SC lipids and effects of terpene penetration enhancers on the permeation of oestradiol and, to some extent, th...

The discovery in September 1991 of a Late Neolithic man in a glacial field in Oetzal between Austria and Italy at a height of 3200m has provided uniquely preserved samples for archaeological studies. The Ice-man (or Similaun man) body is that of a male between 25 and 40 years old who probably died of natural causes some 5200 years ago. Of importanc...

Biomedical studies of hard and soft human tissue using Raman spectroscopy have now become well established and there is quite an extensive literature on normal and diseased skin and organs, single cells, implants and the presence of foreign inclusions following implantation, and the interaction of chemical agents with soft tissues. The advancement...

Previously, we reported a lamellar lipid matrix capable of modelling the structural and barrier properties of the stratum corneum (SC) intercellular lipids and that oestradiol (OE) and 5-fluorouracil (5-FU) permeate the SC through intercellular channels. To investigate the ability of the matrix in modelling the effects of terpene penetration enhanc...

It is widely accepted that the intercellular lipid domain of the stratum corneum (SC) is the main barrier to transdermal permeation of most drugs. Previously, we reported a lamellar lipid matrix capable of modelling the structural properties of the SC intercellular lipids and its barrier performance toward oestradiol (OE) and 5-fluorouracil (5-FU)....

Complex coacervation is the separation of an aqueous mixture of oppositely charged ions into a dense coacervate oil phase, rich in ionic complex, and a dilute equilibrium phase. Coacervation was investigated between cationic tricyclic antidepressants (amitriptyline, imipramine and doxepin) and counter-ions of anionic bile salts sodium cholate (NaC)...

The permeation characteristics through human skin of 8-methoxypsoralen (8-MOP) and its physical attributes were investigated. The log octanol/water partition coefficient and saturated aqueous solubility of 8-MOP at 32°C were 1.98 and 55.8 μg mL−1 respectively. 8-MOP showed Fickian diffusion, with its flux being linearly related to the concentration...

The principal barrier to transdermal delivery of most drugs is the lamellar intercellular lipid matrix of the stratum corneum (SC). Preparation of a model for this matrix provides opportunities to probe the nature of the SC barrier. Here, a method has been developed to construct a model matrix comprising 20% cholesterol, 25% water and 55% SC free f...

The principal barrier to transdermal delivery of most drugs is the lamellar intercellular lipid domain of the stratum corneum (SC). The low permeability of SC in comparison to other lipid barriers is in part due to its geometry. Here, effect of geometry of the SC on permeation of 5-fluorouracil (5-FU) - a model hydrophilic drug - and oestradiol (OE...

The mechanisms through which the terpenes, d-limonene, 1–8-cineole and nerolidol, increase the permeability of human stratum corneum (s.c.) and the mechanisms underlying propylene glycol (PG)/terpene synergy were investigated using differential scanning calorimetry (DSC), small-angle X-ray diffraction (SAXD) and enhancer uptake studies. DSC experim...

The effects of propylene glycol/water co-solvent systems and terpene penetration enhancers (1,8-cineole, menthone, (+)-limonene and nerolidol) on the absorption rate of the model hydrophilic permeant, 5-fluorouracil, were investigated using excised human skin. Similar fluxes for 5-fluorouracil were obtained from saturated enhancer-free co-solvent s...

The molecular state of about 5200-year-old skin from the so-called 'Iceman' (Similaun man or &zi) has been characterised using Fourier transform Raman spectroscopy, and has been compared with that of contemporary man. Contemporary skin was also freeze-dried (to mimic the conditions under which the ancient skin was preserved) and its molecular struc...

Skin samples from the corpse of a late-Neolithic man (5200 years BC) found in a glacier in Oetzal, commonly known as the Ice-man, have been analysed using FT-Raman spectroscopy. Good quality spectra have been obtained and compared with those from contemporary freeze-dried stratum corneum, using a time-dependent FT deconvolution method. This provide...

The stratum corneum, the outermost layer of human skin, is the major barrier to transdermal delivery of most drugs. Dimethyl sulfoxide (DMSO) is an established penetration enhancer. To assess its mechanism of flux enhancement, Fourier transform (FT) Raman spectroscopy was used to study the effects of a series of aqueous solutions of DMSO on hydrate...

One approach to transdermal permeation enhancement investigated in this paper is to increase the thermodynamic activity of a drug in the transdermal delivery system to supersaturation levels. Saturated solubilities of the model drug oestradiol (OE) in different concentrations of propylene glycol/water (PG/W) co-solvent systems were determined. Util...

Recent investigations have shown that human skin permeabilities may not always follow a Gaussian-normal distribution as usually assumed. Permeability coefficients (Kp) for the model hydrophilic permeant, 5-fluorouracil (5-FU), and the model lipophilic permeant, estradiol (ES), were demonstrated to follow more closely log-normal distributions. The p...

Considerable interest in using the transdermal route for drug administration has strengthened the need for investigations of vehicle effects. The influence of ethanol on the in vitro transport behaviour of saturated oestradiol (OE) solutions through excised human skin and model membranes (silastic, human skin-silastic sandwich and snake skin) was i...

Permeation of the model hydrophilic compound 5-fluorouracil was studied through human epidermal membranes treated with penetration enhancers oleic acid in propylene glycol, d-limonene, 1,8-cineole, menthone and nerolidol for times ranging from 1 to 12 h. Partitioning of the drug from aqueous solutions into enhancer treated human stratum corneum was...

Raman spectra have been obtained from normal, healthy human stratum corneum, callus tissue and hyperkeratotic psoriatic plaques. Assignments of the spectra have been made and changes in the 1000–1500 and 2800–3100 cm−1 wavenumber regions have been related to lipid loss in the abnormal tissues but the keratin component is structurally unaltered. The...