Study On The Degradable Poly (Ether-anhydride) Photocrosslinked Gel For Hydrophobic Drugs

The poor solubility of hydrophobic drugs in water and their low dissolution rate in the body fluids often leads to insufficient bioavailability and is one of the most difficult and non-dissolved problems in pharmaceutical industry. Over the years, various solid dosage formulation techniques including solid dispersion,β-cyclodextrin inclusion complex, water-soluble prodrug et al., which enhance the dissolution of poorly soluble substances, have been successfully introduced to some extent. However, some of the formulated drug systems become instable and will recrystallize when they are stored for a period of time. The aim of this work was to explore a method that the hydrophobic drugs were entrapped into the biodegradable poly(ether-anhydride) photocrosslinked gels to increase the dissolution rate and enhance the stability of these drugs .Polyethylene glycol (PEG) and sebacic acid (SA) were chosen as the candidates to construct the matrix of the poly (ether-anhydride) gels due to their excellent properties such as biocompatibility, non-toxicity and non-immunogenicity, which are proved by FDA for widely use in the field of biomedical science. By introducing hydrophilic PEG chain to polyanhydride structures, PEG-based macromers containing anhydride bonds were synthesized and photopolymerized to form degradable gels under UV irradiation. The structures were characterized by FTIR and 1H NMR. Indomethacin (IMC) as a model of poorly water-soluble drug was embedded in the degradable poly (ether-anhydride) photocrosslinked network by two different methods: in situ and post-fabrication. The drug was proved to be distributed with amorphous or molecular state in the crosslinked network and the physical morphology of the drug remained stable after at least 8 months storage by employing X-ray diffraction and differential scanning calorimetery (DSC). Dissolution tests showed that the drug in the network displayed better dissolution rate and more cumulative drug release than the crystal raw indomethacin. This method could increase the dissolution rate, inhibit recrystallization and enhance the stability of indomethacin in the degradable poly (ether-anhydride) networks, which provides a novel method and can be extended to other hydrophobic drugs.