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Benaouda F.,Kings College London | Brown M.B.,MedPharm Ltd. | Brown M.B.,University of Hertfordshire | Ganguly S.,Kings College London | And 2 more authors.
Molecular Pharmaceutics | Year: 2012

There is a need to understand how solvent structuring influences drug presentation in pharmaceutical preparations, and the aim of this study was to characterize the properties of propylene glycol (PG)/water supramolecular structures such that their functional consequences on drug delivery could be assessed. Shifts to higher wavenumbers in the C-H and C-O infrared stretching vibrations of PG (up to 8.6 and 11 cm-1, respectively) implied that water supramolecular structures were being formed as a consequence of hydrophobic hydration. However, unlike analogous binary solvent systems, water structuring was not enhanced by the presence of the cosolvent. Two discrete populations of supramolecular structures were evident from the infrared spectroscopy: water-rich structures, predominant below a PG volume fraction (fPG) of 0.4 (unmoving water bending vibration at 1211 cm -1) and PG-rich structures, predominant above 0.4 fPG (both C-H and water peaks moved to lower wavenumbers). The un-ionized diclofenac log-linear solubility and transmembrane transport altered dramatically when fPG > 0.55 (a 10-fold increase in transport from 0.28 ± 0.06 μgcm-2h-1 at 0.2 fPG to 2.81 ± 0.16 μgcm-2h-1 at 0.9 fPG), and this demonstrated the ability of the PG rich supramolecular structures, formed in the PG/water solvent, to specifically modify the behavior of un-ionized diclofenac. © 2012 American Chemical Society.


Wood D.G.,MedPharm Ltd. | Wood D.G.,Kings College London | Brown M.B.,MedPharm Ltd. | Brown M.B.,University of Hertfordshire | Jones S.A.,Kings College London
European Journal of Pharmaceutics and Biopharmaceutics | Year: 2012

The application of moderate heat is a safe and effective means to increase drug transport across human skin. However, the cascade of events that follows the exposure of a topical skin formulation to a heating source is not well understood. The aim of this study was to elucidate how three potential rate limiting stages in the drug transport process; formulation release, drug partitioning and epidermal diffusion, responded to changes in local temperature using the model drug lidocaine. Release from the formulation measured using regenerated cellulose membrane was shown to be driven by drug diffusion in the vehicle; it responded linearly when the local temperature was changed (21.6 μg/cm2/h for every 1°C rise) and displayed no measurable partitioning of lidocaine into RCM. Once the drug was within the human epidermis, the structural changes of the barrier controlled its transport. The apparent lidocaine diffusion coefficient through silicone membrane increased from 6.52 to 8.43 × 10-4 over the 32-45°C temperature range, but it increased from 7.74 × 10-5 cm2 h -1 to 4.8 × 10-4 cm2 h-1 in the human epidermis. In the absence of large increases in drug partitioning, fluidisation of the lipids in the upper layers of the epidermis at 37-45°C was shown to facilitate lidocaine diffusion which for human skin transport was the rate limiting process. © 2012 Elsevier B.V. All rights reserved.


Zhao Y.,Tianjin University | Zhao Y.,Kings College London | Jones S.A.,Kings College London | Brown M.B.,University of Hertfordshire | Brown M.B.,MedPharm Ltd.
Journal of Pharmacy and Pharmacology | Year: 2010

Objectives: Pharmaceutical foams are not new inventions and their application in topical therapy can be traced back three decades. However, foam formulations have been gaining in popularity with over 100 patents published globally in the last 10 years alone. The aim of this paper is to review the current status and explore the future potential of dynamic foam vehicles in the field of topical drug delivery. Key findings: The use of foam technology to deliver a range of topical active agents has been claimed, including sun-screening compounds, corticosteroids, and antibacterial, antifungal and antiviral agents. Although foams present distinct application advantages and improved patient compliance, the real reason for the rapid growth of topical foam technology is that foams as elegant, aesthetic and cosmetically appealing vehicles provide an alternative, promising formulation strategy in the highly competitive dermatological market. Although there is a plethora of published data proving the safety profiles of topical foams there is a lack of sufficient clinical evidence to demonstrate any superiority of foams over other traditional topical vehicles such as creams and ointments for drug delivery. Summary: Recent literature suggests that when foams are properly engineered using the advances of in situ analysis techniques, the enhancement of topical drug delivery via engineering this type of vehicle can be achieved. © 2010 Royal Pharmaceutical Society of Great Britain.


Zhao Y.,Kings College London | Brown M.B.,MedPharm Ltd. | Brown M.B.,University of Hertfordshire | Jones S.A.,Kings College London
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2010

Nanoparticulate systems have the potential to improve topical drug delivery because of their capacity to enhance drug loading and dissolution, protect chemically unstable therapeutic agents, and improve product aesthetics. However, the commercial use of nanoparticles in topical products is limited because the evidence that they penetrate intact skin is contradictory, and their ability to release active agents in traditional semisolid vehicles is poor. One way to overcome this problem is to formulate nanoparticles in a dynamic delivery system-that is, one that induces a change upon dose actuation so as to promote drug release. Pressurized pharmaceutical foams are one type of dynamic system that can drive a change of state and excipient concentration after dose actuation. This review summarizes the current status of topical products containing nanoparticles, discusses the recent scientific advances in foam production, and investigates the prospect of incorporating nanoparticles into dynamic topical foams. Recent literature suggests that dynamic foams have the potential to break down the nanoparticles loaded within them, improve drug release from nanoparticles, and enhance topical efficacy. Although the published data to support the use of dynamic systems are limited, it is clear that they provide a promising solution to enhance drug release from nanoparticles, and future research work should aim to investigate these systems in more detail. From the Clinical Editor: The use of nanoparticulate systems in topical products is limited as skin penetration and release of active agents remains controversial. Pressurized pharmaceutical foams represent a dynamic system characterized by a change of state and excipient concentration after dose actuation. The review summarizes the current status of topical nanoparticles utilizing this delivery system. © 2010 Elsevier Inc. All rights reserved.


Ali J.,University of Hertfordshire | Camilleri P.,Bio Chemical Solutions | Brown M.B.,University of Hertfordshire | Brown M.B.,MedPharm Ltd. | And 2 more authors.
Journal of Chemical Information and Modeling | Year: 2012

The General Solubility Equation (GSE) is a QSPR model based on the melting point and log P of a chemical substance. It is used to predict the aqueous solubility of nonionizable chemical compounds. However, its reliance on experimentally derived descriptors, particularly melting point, limits its applicability to virtual compounds. The studies presented show that the GSE is able to predict, to within 1 log unit, the experimental aqueous solubility (log S) for 81% of the compounds in a data set of 1265 diverse chemical structures (-8.48 < log S < 1.58). However, the predictive ability of the GSE is reduced to 75% when applied to a subset of the data (1160 compounds -6.00 < log S < 0.00), which discounts those compounds occupying the sparsely populated regions of data space. This highlights how sparsely populated extremities of data sets can significantly skew results for linear regression-based models. Replacing the melting point descriptor of the GSE with a descriptor which accounts for topographical polar surface area (TPSA) produces a model of comparable quality to the GSE (the solubility of 81% of compounds in the full data set predicted accurately). As such, we propose an alternative simple model for predicting aqueous solubility which replaces the melting point descriptor of the GSE with TPSA and hence can be applied to virtual compounds. In addition, incorporating TPSA into the GSE in addition to log P and melting point gives a three descriptor model that improves accurate prediction of aqueous solubility over the GSE by 5.1% for the full and 6.6% for the reduced data set, respectively. © 2011 American Chemical Society.

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