Stability of 5-aminolevulinic acid in novel non-aqueous gel and patch-type systems intended for topical application.

Aminolevulinic acid (ALA) stability within topical formulations intended for photodynamic therapy (PDT) is poor due to dimerisation to pyrazine-2,5-dipropionic acid (PY). Most strategies to improve stability use low pH vehicles, which can cause cutaneous irritancy. To overcome this problem, a novel approach is investigated that uses a non-aqueous vehicle to retard proton-induced charge separation across the 4-carbonyl group on ALA and lessen nucleophilic attack that leads to condensation dimerisation. Bioadhesive anhydrous vehicles based on methylvinylether-maleic anhydride copolymer patches and poly(ethyleneglycol) or glycerol thickened poly(acrylic acid) gels were formulated. ALA stability fell below pharmaceutically acceptable levels after 6 months, with bioadhesive patches stored at 5°C demonstrating the best stability by maintaining 86.2% of their original loading. Glycerol-based gels maintained 40.2% in similar conditions. However, ALA loss did not correspond to expected increases in PY, indicating the presence of another degradative process that prevented dimerisation. Nuclear magnetic resonance (NMR) analysis was inconclusive in respect of the mechanism observed in the patch system, but showed clearly that an esterification reaction involving ALA and both glycerol and poly(ethyleneglycol) was occurring. This was especially marked in the glycerol gels, where only 2.21% of the total expected PY was detected after 204 days at 5°C. Non-specific esterase hydrolysis demonstrated that ALA was recoverable from the gel systems, further supporting esterified binding within the gel matrices. It is conceivable that skin esterases could duplicate this finding upon topical application of the gel and convert these derivatives back to ALA in situ, provided skin penetration is not affected adversely.

Molecular Hydrogen Emission from Protoplanetary Disks

We have modeled self-consistently the density and temperature profiles of gas and dust in protoplanetary disks, taking into account irradiation from a central star. Making use of this physical structure, we have calculated the level populations of molecular hydrogen and the line emission from the disks. As a result, we can reproduce the observed strong line spectra of molecular hydrogen from protoplanetary disks, both in the ultraviolet (UV) and the near-infrared, but only if the central star has a strong UV excess radiation.

Passive Control of Plume Interference on Slender Axisymmetric Bodies

The physics of the plume-induced shock and separation, particularly at high plume to exit pressure ratios with and without shock-turbulent boundary-layer control methods, were studied using computational techniques. Mass-averaged Navier-Stokes equations with a two-equation turbulence model were solved by using a fully implicit finite volume scheme and time.marching algorithm. The control methodologies for shock interactions included a porous tail and a porous extension attached at the nozzle exit or trailing edge. The porous tail produced a weaker shock and fixed the shock position on the control surface. The effect of the porous extension on shock interactions was mainly to restrain the plume from strongly underexpanding during a change in flight conditions. These techniques could give an additional dimension to the design and control of supersonic missiles.