Susan Jones

Critical Characteristics for Corticosteroid Solution Metered Dose Inhaler Bioequivalence

Determining bioequivalence for solution pressurized metered dose inhalers (pMDI) is difficult because the critical characteristics of such products are poorly defined. The aim of this study was to elucidate the non-aerodynamic properties of the emitted aerosol particles from two solution pMDI products that determine their biopharmaceutical differences after deposition. Novel particle capture and analysis techniques were employed to characterize the physicochemical and biopharmaceutical properties of two beclomethasone dipropionate (BDP) products: QVAR and Sanasthmax. The BDP particles emitted from the Sanasthmax inhaler were discernibly different those emitted from QVAR in terms of size (50% larger, less porous), solid state (less crystalline) and dissolution (20-fold slower). When deposited onto the surface of respiratory epithelial cell layers, QVAR delivered ∼50% more BDP across the cell layer in 60 min than Sanasthmax. Biopharmaceutical performance was not attributable to individual particle properties as these were manifold with summative and/or competing effects. The cell culture dissolution-absorption model revealed the net effect of the particle formed on drug disposition and was predictive of human systemic absorption of BDP delivered by the test inhalers. This illustrates the potential of the technique to detect the effect of formulation on the performance of aerosolized particles and contribute to assessment of bioequivalence.

Novel strategy for enhancing transdermal drug delivery

The concept that the time to onset of erythema after the application of the rubefacient and urticant substance methyl nicotinate (MN) indicates skin barrier competence was introduced 30 years ago. MN produces a dose-dependent erythema on topical application to intact skin, the nature of which is known to be fast moving (in the order of minutes) and variable. Using tissue viability imaging (TiVi) the time course and degree of the reaction can be conveniently followed and analysed. Inter-individual variability can be quite marked but intra-individual variability is less pronounced. At the upper end of provocation (higher doses, more sensitive individuals) urtication can occur, which decreases blood flow by increasing pressure on and thus emptying capillaries. The TiVi system can quantitate urtication and inherent (blanched) skin colour. The utility of MN application in the study of individual barrier function and microvascular reactivity is increased by the use of the TiVi system for collection and analysis of data.

The Effect of Disulphide Bond Disruption on the Barrier Integrity of the Human Nail

Onychomycosis is the fungal infection of the nail and accounts for approximately 50% of all nail disorders [1]. The prevalence of onychomycosis is increasing and currently up to 10 % of people in the UK and US are reported to be affected by this condition [2,3]. It can be both physically and psychologically debilitating during the most progressive stages of the disease [4,5]. Fungi (most frequently Trichophyton rubrum and Trichophyton mentagrophytes), moulds (Scytalidium spp, Scopulariopsis spp, Fusarium spp, Acremonium spp, Onychocola canadensis) and yeasts (Candida spp) can be co-resident in a diseased nail and hence not every nail can be considered as being populated by the same community of species.

The effect of temperature on the diffusion of lidocaine base

time required so as to observe full hydrolysis. As such, the compounds were exposed to the basic conditions and ‘assay’ run until the complete hydrolysis of the compounds, and the half-life of each compound determined from the plot of absorbance against time. Results In the development of the assay, we considered the hydrolysis reaction and, in particular, the half-life of the compounds under basic conditions. That is, we concluded that the mimicking of the gem-diol within the active site of ES is best undertaken through the use of HO (e.g. through the use of alcoholic NaOH). As such, we considered the time taken for the full hydrolysis of the sulphonate moiety and therefore monitored the production of the phenolic product. From our results, we discovered that the previously reported acetateand formate-based inhibitors possess a greatly reduced half-life in comparison with the methanesulphonate derivatives (for example, the half-life for the methanesulphonate derivative of 4-hydroxyacetophenone was approximately 77 minutes whereas for the acetate derivative it was approximately 5 minutes; it should be noted that the time for the aminosulphonates was found to be less than 1 minute). As such, this would appear to suggest that the mechanism of action of these two ranges of compounds is similar; that is, hydrolysis of the sulphonate/carboxylate moieties. Conclusions We have therefore provided a novel non-enzymatic methodology that has been utilized successfully in the study of the mechanism of different ranges of inhibitors of ES.The in vitro loading and subsequent elution of topotecan (used to treat a variety of cancers) from drug-eluting beads (DEBs) was assessed, while evaluating the effects of selected physical attributes (size and compressibility)

The effect of complex coordination on gallium determination using ion chromatography

Objectives Indian basil or Ocimum basilicum L. is a holy plant and widely used to cure various ailments including skin diseases. In the present investigations, scientific validation of the wound-healing properties of leaves of O. basilicum was carried out along with investigation into the quality parameters of the extracts used for the study. Methods Fresh leaves of Ocimum basilicum L. were collected, dried, powdered and extracted with three different solvents (water, alcohol and hydroalcohol (25%)) by maceration for 72 hours with occasional shaking. All the extracts were concentrated under reduced pressure and at lower temperature using a rotary evaporator; after this they were dried. High-performance thin-layer chromatography fingerprinting of the dried extracts was developed. Swiss albino mice of 25–30 g in weight were used for the experiment and approved by the ethical committee of our institute. Animals were anaesthetized under ketamine anaesthesia (intraperitoneal 10 mg/kg) and an area of approximately 4 cm on the dorsal surface was clipped free of hair and swabbed with 70% ethanol. The cleared dorsal surface of the skin was marked with a sterile circular (10 mm diameter) stainless steel stencil. A full-thickness wound was created by excising the skin flap in an aseptic environment using sterile scissors and forceps. The mice were divided into five groups (n = 5). Group I was kept as a control group, group II was kept as a positive control and treated with marketed formulation (0.5% w/w povidone iodine ointment) and groups III, IV and V were treated with the aqueous, hydroalcoholic and alcoholic O. basilicum extracts topically on the wound daily up to the 16th day after wounding. Results To evaluate the wound-healing potential of O. basilicum, hydroxyproline content and percentage wound contraction were estimated. Hydroxyproline content is an index of collagen and measures the synthesis of neocollagen, which is an indicator of improved condition of wound healing in animals. Hydroxyproline was estimated (Woessner 1961) from granulation tissues of animals on the 16th day after wound creation. The levels of hydroxyproline were found to be 6.40 ± 1.09, 7.10 ± 2.53, 10.11 ± 1.26, 14.95 ± 1.87 and 8.52 ± 1.28 mg/g of tissue in groups I–V, respectively. Hydroxyproline level was significantly higher (P < 0.05) in animals treated with hydro-alcoholic extract (group IV). Wound contraction indicates the rate of reduction of an unhealed area during the course of treatment; the greater the reduction the better the efficacy of the medication (Peacock 1984). Wound contraction was measured by tracing the wound margins at 4-day intervals on transparent graph paper with a millimetre scale to an accuracy of 0.05 mm. The wound-contraction data are shown in Table 1. Conclusions In conclusion, the hydro-alcoholic extract of O. basilicum leaves showed significant wound-healing properties in this excision-wound model.