The Pharmaceutical Journal
Vol 277 No 7417 p316
9 September 2006

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British Pharmaceutical Conference 2006

A taster of the science presentations

Scientists from around Britain gathered at the British Pharmaceutical Conference to present their work to peers and colleagues. A selection of some of their work is reported below.

Needle-free immunisation

Needle-free immunisation is desirable due to inherent needle-associated problems, and alternative ways of vaccination are sought. Needle usage can spread blood-borne diseases if someone is accidentally pricked with a needle, or if a needle is reused, and painless and safe administration needs a trained nurse or doctor, said Afendi Dahlan, of the London School of Pharmacy, leading new research to develop needle-free immunisation. Low-frequency ultrasound has been shown to assist transcutaneous vaccination, and work at the school has concentrated on the best conditions to make this mode of needle-free vaccination feasible. Pulses of ultrasound were applied to mouse skin wetted with water or varying concentrations of a sodium dodecyl sulphate solution. Vaccine (tetanus toxoid) solution was then applied to the treated skin, with booster doses after 15 and 46 days. Serum was tested for antibodies to assess the efficiency of vaccine delivery. Effective delivery was achieved when ultrasound was combined with the sodium dodecyl sulphate solution; ultrasound treatment alone resulted in increased antibody titres only after a second boost when it was comparable to that achieved by an intramuscular injection. Including even low concentrations of sodium dodecyl sulphate in the wetting solution resulted in increased immune responses even after the first dose. The lower sodium dodecyl sulphate concentration would have the advantage of less skin irritancy.

Methadone reefers

As little as 20 per cent of the dose of methadone in a 30mg reefer is inhaled, reported L. S. Briscoe on work carried out at Liverpool John Moores University. Most patients receive their methadone replacement therapy in the form of an oral liquid or an intravenous injection. However, some are prescribed reefers, usually containing 30mg or 60mg of methadone per cigarette. The use of reefers as a delivery system poses a number of important questions. What proportion of the methadone is available to the patient and how much is lost during combustion? What combustion products may be inhaled and could they be considered toxic? What may be the impact of change in the base material from tobacco to some other herb? In the Liverpool study, 30mg methadone reefers were combusted so as to allow collection of the mainstream smoke, sidestream smoke, ash, filter and the oily deposit carried by the smoke. The data obtained indicated that approximately 44 per cent of the methadone in a reefer was recovered from the various fractions collected. Of this, half was found in the filter and half in the combined smoke fractions. Although the amount actually inhaled by a patient using a reefer would depend on factors such as duration and vigour of inhalation, factors that would modulate the mainstream:side-stream smoke ratio, it would appear that only approximately 20 per cent of the dose of methadone in a 30mg reefer would be inhaled. Extracts of the mainstream smoke revealed the presence of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, which has previously been reported as a urinary metabolite in methadone patients.

Drug release from silicone elastomers

The highly hydrophobic nature of conventional silicone elastomers used in controlled drug delivery devices limits the utility of such systems to relatively hydrophobic molecules such as steroids. From both a medical device and a drug delivery perspective, there is currently much interest in developing novel silicone elastomer biomaterials that have enhanced hydrophilicity as a result of modifications made to either the entire elastomer system or only its surface. M. C. McBride and co-workers, from the Queen’s University of Belfast, reported on the successful development of silicone elastomers modified to present poly(ethyleneglycol) functional groups on the elastomer. When fluoxetine hydrochloride, zidovudine or testosterone was incorporated into the modified elastomer, the in vitro release of the drug was facilitated by a degree related to its hydrophobicity. Such modified silicone elastomers could be used in medical devices which would release drugs not released from conventional silicone elastomer systems.

Folk medicine may overcome MRSA

New research has given strong support to the folkloric use of a traditional Ghanaian medicine that may be useful in the treatment of methicillin-resistant Staphyllococcus aureus, reported Kofi Annan, of King’s College London. The leaves, stems and roots of Paullinia pinnata are used by people in different communities in Central Africa for the treatment of wounds and other microbial infections. In the King’s study, bioassay-guided fractionation of a methanol extract of the plant led to the isolation of seven compounds from the active fractions using column chromatography and thin-layer chromatography. These compounds were assessed for their antibacterial activities against different resistant strains of Staphylococcus aureus. The antioxidant and fibroblast stimulation action of the crude extract and the isolated compounds were also assessed. Five compounds had antibacterial effects; the most active was also shown to potentiate the activity of norfloxacin, tetracycline and erythromycin against resistant strains, suggesting that the folk medicine may have a role in combating MRSA. Extracts of the plant were also shown to have strong radical scavenging activity and a strong fibroblast stimulatory action. Identification of the isolated active compounds is under way.

Crystallisation in transdermal patches

Unwanted crystallisation of drug compound in transdermal patches will lead to the drug not being available for absorption. Studies on prevention of crystallisation of ibuprofen in such formulations were reported by Kalliopi Dodou, of the University of Sunderland. When silicone polymers were mixed with ibuprofen as the adhesive layer, white crystals of the drug could be clearly seen on storage when examined under a microscope. When an acrylic polymer was used the layer remained clear even without addition of other crystallisation inhibitors. Release of ibuprofen from the acrylic layers, determined by a dissolution test, was also superior to release from silicone polymers. Dr Dodou suggests that acrylic-based adhesives are good candidates for further development of drug-in-adhesive formulations of ibuprofen.

Processing live mammalian cells

Supercritical carbon dioxide processing is a method of fabricating porous polymer scaffolds for tissue engineering applications without organic solvents and high temperatures. When above its critical point, CO₂ can dissolve into amorphous polymers such as poly(DL-lactic acid) causing them to plasticise, before subsequent decompression causes the formation of gas bubbles that become permanent as the polymer vitrifies. This has enabled thermally labile biomolecules to be entrapped within controlled-release matrices using a single processing step. Kevin Shakesheff and colleagues, from the University of Nottingham, have extended the principle to incorporate a variety of live mammalian cells into biodegradable scaffolds. By using short exposure times any toxic effect of the supercritical CO₂ on the cells was minimised. The result was to remove the time-consuming and frequently inefficient two-step scaffold seeding process required in many cell-based tissue engineering strategies.