The Incorporation and Controlled Release of Anionic Drugs from a Polypyrrole Membrane Film
Ryan, Eimear M. (2010) The Incorporation and Controlled Release of Anionic Drugs from a Polypyrrole Membrane Film. PhD thesis, National University of Ireland Maynooth.
In this thesis, results are presented and discussed on the synthesis and characterisation of polypyrrole (PPy) doped with various anionic drugs. The drugs, which were small to medium‐large in size, included the aqueous soluble dexamethasone 21‐phosphate disodium (NaDex) and valproic acid sodium (NaVPA) salts, and the less soluble diclofenac sodium (NaDF) salt. Two other drugs, indomethacin sodium (NaIndo) and sulindac sodium (NaSul) with very imited solubility in aqueous solution, were chosen. r l The incorporation of dexamethasone (Dex2‐) and diclofenac anions (DF‐) within the PPy membrane was achieved by a potentiostatic mode of growth from an aqueous solution of pyrrole and the drug under investigation. For the PPy doped with Dex2‐, characterisation and release studies found the doping level of the polymer to be about 0.30, and approximately 31 μmol cm‐2 of Dex2‐ was incorporated into the polymer upon polymerisation. Furthermore, it was observed that the rate of release could be controlled by the potential applied with approximately 89 % of the Dex2‐ released within 60 min at an applied potential of – 0.900 V vs SCE. For the PPy doped with DF‐, unusual patterns in growth and morphology were observed. During the deposition of the polymer, the rate of polymerisation decreased with increasing time and higher applied potentials. The polymer had features of an insulating film, as evident from electrochemical impedance measurements, while SEM confirmed the presence of crystal‐like shards on the surface of the polymer. These findings suggest that insoluble drug crystals are formed during polymerisation. DF‐ displays a limited solubility in aqueous solutions and during the oxidation of the monomer and drop of pH at the surface, the equilibrium is shifted from the soluble DF‐ towards the insoluble HDF causing insoluble crystals of the drug to deposit on the surface of the polymer, which hinders further polymerisation. The incorporation of two insoluble medium sized drugs, NaIndo and NaSul, into the PPy film was also investigated. Deposition of PPy doped with either of the drugs in question was carried out in ethanol and tetrabutylammonium perchlorate (TBAP) was added to increase the conductivity. It was found that the PPy films formed in this organic medium were not as conducting as those formed in the aqueous solution, and doping levels were considerably lower than those previously reported for PPy. The addition of the TBAP introduces the small and mobile, ClO4‐, anion which is well known to dope PPy. UV‐visible spectroscopy was used to calculate that approximately 2.19 x 10‐6 mol cm‐2 of ClO4‐ was present in the polymer. However, this is quite minute compared to the estimated amount of drug doped within the polymer; 260 μmol cm‐2 and 60 μmol cm‐2 of Indo‐ and Sul‐, respectively. As seen with the other polymers the rate of release was controlled by the applied potential. Finally, the formation of PPy doped with a small soluble anionic drug, VPA‐, was studied. Although this was the smallest of all the drugs studied, it was not possible to incorporate this drug into the PPy membrane electrochemically. This was explained in terms of the solubility of the anion at low pH values. At pH values below 5.6 the equilibrium of the VPA‐ is shifted towards the insoluble HVPA. As the monomer is oxidised, there is a decrease in the local pH in the vicinity of the electrode and this causes the HVPA to precipitate from solution. This, in turn, prevents any PPy from being deposited at the electrode. Vapour phase polymerisation is offered as an alternative approach to immobilise this drug into the PPy film.
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