Abstract: The aim of this study was to develop a stomach-specific drug delivery system to increase the efficacy of amoxicillin against Helicobacter pylori. Polyacrylic acid (PAA), chitosan (CS), and amoxicillin (A) were employed to obtain polyionic complexes. The design of the hydrogel delivery system was based on the swellable approach; with a floating feature to prolong the Gastric Residence Time (GRT). The polyionic complex (PAA:CS:A 2.5:5:2) showed a sustained drug release profile in enzyme-free simulated gastric fluid (SGF) and pH 4.0. A pH independent swelling-eroding pattern with adequate maximum swelling ratios of 17.76 and 13.42 was obtained at in SGF and pH 4.0, respectively, with similar eroding profiles in both pH media. This network carrier provides an amoxicillin protective effect towards the hydrolytic degradation in SGF. The in vivo study was performed on healthy volunteers, using the [13C] octanoic acid breath test. The proposed hydrogel showed a prolonged GRT of up to 3 h. The preliminary results from this study suggest that amoxicillin polyionic complexes have potential for improving local antibiotic therapy against H. pylori.
Abstract: The aim of this study was to develop a chitosan-poly(acrylic) acid based controlled drug release system for gastric antibiotic delivery. Different mixtures of amoxicillin (A), chitosan (CS), and poly(acrylic) acid (PAA) were employed to obtain these polyionic complexes. A non-invasive method was employed for determining the gastric residence time of the formulations. It was studied the swelling behavior and drug release from these complexes. Gastric emptying rate study was performed by means of the [13C]octanoic acid breath test. The gastric emptying rates of two different formulations (conventional and gastric retentive system) were studied. Swelling studies indicated that the extent of swelling was greater in the polyionic complexes than in the single chitosan formulations. The amoxicillin diffusion from the hydrogels was controlled by the polymer/drug interaction. The property of these complexes to control the solute diffusion depends on the network mesh size, which is a significant factor in the overall behavior of the hydrogels. The gastric half-emptying time of the polyionic complex was significantly delayed compared to the reference formulation, showing mean values of 164.32+/-26.72 and 65.06+/-11.50min, respectively (P<0.01). The results of this study suggest that, these polyionic complexes are good systems for specific gastric drug delivery.
Abstract: Non-covalent polyionic complexes were developed for localized antibiotic delivery in the stomach. Freeze-dried interpolymer complexes based on polyacrylic acid (PAA) and chitosan (CS) were prepared in a wide range of copolymer compositions by dissolving both polymers in acidic conditions. The influence of hydrogel-forming medium on the swelling and drug release was evaluated. The properties of these complexes were investigated by using scanning electron microscopy, dynamic swelling/eroding and release experiments in enzyme-free simulated gastric fluid (SGF). The electrostatic polymer/polymer interactions generate polyionic complexes with different porous structures. In a low pH environment, the separation of both polymer chains augmented as the amount of cationic and carboxilic groups increased within the network. However, the presence of higher amount of ions in the hydrogel-forming medium produced a network collapse, decreasing the maximum swelling ratio in SGF. PAA:CS:A (1:2.5:2)-1.75 M complexes released around 54% and 71% of the amoxicillin in 1 and 2 h, respectively, in acidic conditions. A faster drug release from this interpolymer complex was observed when the ionic strength of the hydrogel-forming medium increased. Complexes with a high amount of both polymer chains within the network, PAA:CS:A(2.5:5:2), showed a suitable amoxicillin release without being affected by an increased amount of ions in the hydrogel-forming medium. These freeze-dried interpolymer complexes could serve as potential candidates for amoxicillin delivery in an acidic enviroment.
Abstract: Polyionic complexes of chitosan (CS) and poly(acrylic acid) (PAA) were prepared in a wide range of copolymer composition and with two kind of drugs. Release of amoxicillin trihydrate and amoxicillin sodium from these different complexes were studied. The swelling behavior of and solute transport in swellable hydrogels were investigated to check the effect of polymer/polymer and polymer/drugs interactions. The electrostatic polymer/polymer interactions take place between the cationic groups from CS and the anionic ones from PAA. The diffusion of amoxicillin trihydrate was controlled only by the swelling/eroding ratio of the polyionic complexes. The swelling degree of amoxicillin sodium hydrogels was more extensive when compared to the swelling degree of amoxicillin trihydrate formulations. It was concluded that the water uptake was mainly governed by the degree of ionization. Restriction of amoxicillin sodium diffusion could be achieved by polymer/ionized-drug interaction that retards the drug release. Freeze-dried polyionic complexes could serve as suitable candidates for amoxicillin site-specific delivery in the stomach.
Abstract: Solid dispersions of praziquantel(PZQ) containing varying concentrations of polyvinylpyrrolidone(PVP) with different molecular weights (3000, 11000 and 34000) were prepared in an attempt to improve the solubility and dissolution rate of PZQ. The physical characteristics of PZQ, physical mixtures and solid dispersions were investigated by a variety of analytical methods including scanning electron microscopy(SEM), differential scanning calorimetry(DSC) and powder X-ray diffraction(XRD). The solubility of PZQ in the coprecipitate was greater when PVP of a smaller molecular weight was used. The dissolution rate of the drug in the coprecipitate was faster when the ratio of the drug to PVP was smaller (1:9). SEM was especially useful in the verification of possible PZQ inclusion in the PVP matrix due to the morphological and physical differences between PZQ and PVP. The physical mixture and solid dispersion DSC scans did not present a clear endothermic peak, perhaps due to a low PZQ enthalpy. The dissolution rate was significantly increased when the PZQ:PVP ratio was at least 1:5, which agrees with the inclusion of PZQ in the PVP matrix, as observed by SEM, and the amorphous pattern shown by XRD.
