ABSTRACT
Gellan gum was chemically modified by the reaction with methacrylic anhydride to produce derivatives with 6, 14 and 49% methacrylation. The structure and substitution degrees of these derivatives were confirmed by 1H NMR- and FTIR-spectroscopy. These derivatives are more hydrophobic compared to pristine gellan and form turbid solutions in water. In vitro study performed with formulations of sodium fluorescein containing gellan gum and its methacrylated derivatives indicated that methacrylation enhances their retention on bovine conjunctival mucosa. In vivo experiments with the formulations of pilocarpine hydrochloride containing gellan gum and methacrylated derivatives have demonstrated that all polymers enhance the drug effect significantly, but best performance is observed for the polysaccharide with 6% methacrylation.
Subject(s)
Conjunctiva/metabolism , Miotics/administration & dosage , Pilocarpine/administration & dosage , Polysaccharides, Bacterial/chemistry , Adhesiveness , Animals , Cattle , Chemistry, Pharmaceutical , Drug Carriers/chemistry , Female , Fluorescein/chemistry , Gels , Hydrophobic and Hydrophilic Interactions , Male , Methacrylates/chemistry , Methacrylates/metabolism , Miotics/chemistry , Miotics/metabolism , Mucous Membrane/metabolism , Pilocarpine/chemistry , RabbitsABSTRACT
This work aimed to investigate the feasibility to design: (a) a mucoadhesive interpolyelectrolyte complex (IPEC) loaded with clobetasol propionate (CP) intended to treat oral lichen planus and (b) individuate an orodispersible dosage form suitable for its administration. IPECs were synthesized by mixing Eudragit® E PO (EPO) and different grades of cross-linked polyacrylate derivatives, in different molar ratios, namely 1:1, 1:2, and 2:1. All IPECs resulted at nanoscale independently of their composition (120â»200 nm). Both zeta-potentials (ζ) and mucoadhesive performances were influenced by the ratio between polymers. On the bases of the preliminary data, IPECs made of Polycarbophil and EPO in the 1:2 ratio were loaded with CP. The encapsulation efficiency was up 88% independently of the CP-IPEC ratio. The drug encapsulation caused IPEC destabilization in water, as it was noticed by the increase of ζ values and the formation of aggregates. Oral lyophilisates were prepared by freeze-drying slurries made of placebo or CP loaded IPECs, maltodextrin with a dextrose equivalent 38 and Span®80. The optimized formulation permitted to obtain a fast disintegration upon contact with water reducing the tendency of IPECs to aggregate. Moreover, oral lyophilisates allowed improving the apparent solubility of CP throughout the in vitro release experiment.
ABSTRACT
With a view to the application in oral controlled drug delivery systems (DDS), the design of new interpolyelectrolyte complexes (IPECs) between countercharged types of Eudragit EPO (EPO) and Eudragit L 100-55 (L100-55) was investigated. The formation and composition of four new IPECs between EPO and L100-55 were established by elementary analysis. The structure of the synthesized IPEC was investigated using FTIR spectroscopy and modulated-temperature differential scanning calorimetry. The binding ratio of a unit molecule of EPO with L100-55 was found to range between 1:2.75 (Z = 0.36) and 1:0.55 (Z = 1.81) while increasing the pH value from 5.5 to 7.0. As a result of electrostatic interaction between the copolymer chains, the glass transition temperature of the IPEC increased significantly. A large pH-sensitive swelling behavior was observed for different structures of the IPECs. The outcome of swelling and diclofenac sodium release from the polycomplex matrices confirm that they have great potential to be used as a controlled DDS in specified regions of gastrointestinal tract.
