Susana Torrado

Release of amoxicillin from polyionic complexes of chitosan and poly(acrylic acid). study of polymer/polymer and polymer/drug interactions within the network structure

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.

Chitosan-poly(acrylic) acid polyionic complex: in vivo study to demonstrate prolonged gastric retention.

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.

Interpolymer complexes of poly(acrylic acid) and chitosan: influence of the ionic hydrogel-forming medium

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.

Preparation, dissolution and characterization of albendazole solid dispersions

In this study, solid dispersion systems of the sparingly water soluble drug, albendazole (ABZ), were mixed with varying concentrations of polyvinylpyrrolidone (PVP K 12) in an attempt to improve the solubility and dissolution rate of ABZ. Physical characteristics were investigated by Powder X-ray diffraction. As expected, the albendazole dissolution rate, expressed as the dissolution efficiency, and also the solubility coefficient were increased when albendazole was mixed with PVP. An increase in the concentration of the polymer in the solid dispersion produced an increase in both parameters. The powder X-ray diffraction patterns showed that the solid dispersion presented an amorphous form of albendazole in this coprecipitate system.

Gentamicin release from modified acrylic bone cements with lactose and hydroxypropylmethylcellulose.

Modified polymethylmethacrylate (PMMA) bone cements formulations were prepared by including different proportions of gentamicin and release modulators such as lactose or hydroxypropylmethylcellulose (HPMC). Surface aspect, gentamicin release and porosity of these modified formulations were studied by means of scanning electron microscopy (SEM), a specially designed system for the dissolution studies of the bone cements, and mercury intrusion porosimetry. Lactose modified cements presented an irregular surface with numerous hollows and voids due to the lactose dissolution. HPMC cements presented a characteristic laminated and flaky surface. The drug release of lactose formulations was up to four-fold greater (13%) than the commercial bone cement CMW1 Gentamicin one (3%). The amount of gentamicin eluted at the first withdrawn sample ranged from 30% to 60% of total gentamicin released over the assay. Gentamicin release from lactose formulations increased as lactose percentage was increased which agree with the porosity results. Nevertheless, the use of release modulator HPMC increased porosity, but did not produce an increase in the gentamicin release. HPMC dissolution creates a surrounding sticky and viscous medium similar to a gel that makes the gentamicin release from the cement matrix difficult.

A validated quantitative colorimetric assay for gentamicin

A colorimetric procedure was developed for the quantification of gentamicin. The method was based on the ninhydrin reaction with primary and secondary amines present in the gentamicin. This reaction produces a purple colour. The effects of several factors including pH, ninhydrin concentration and reaction time were investigated to optimize the assay method. Using the assay protocol, the absorption of the gentamicin-ninhydrin mixtures at 400 nm had a linear relationship with the gentamicin concentration ranging from 30 to 120 microg/ml. The colorimetric gentamicin assay reported herein is of great practical value because it is reproducible, sensitive, simple and extremely inexpensive.

A novel formulation of albendazole solution: oral bioavailability and efficacy evaluation

To improve the oral bioavailability of albendazole, a poorly water-soluble drug, a new liquid formulation was investigated in mice. The liquid formulation studied was a solvent system of Transcutol® (40% w/w) in 1.2 pH buffer. A significant (p<0.05) increased relative bioavailability was obtained with this albendazole solution as compared with an albendazole suspension. A Trichinella/mouse model was used to evaluate the efficacy of the formulation against the different stages of the parasite. The higher concentration–time plasma profile of the albendazole solution would explain the greater therapeutic effect obtained with this new formulation against the systemic phases of the Trichinella model studied. This albendazole solution presented an efficacy against the migrating larvae phase twice that of the albendazole suspension. The efficacy of the solution (95.5%) in the encysted phase was significantly (p<0.05) higher than the efficacy obtained with the albendazole suspension (2.4%).

Comparison of derivative spectrophotometric and liquid chromatograpic methods for the determination of omeprazole in aqueous solutions during stability studies

A first derivative spectrophotometric method was developed for the determination of omeprazole in aqueous solutions during stability studies. The derivative procedure was based on the linear relationship between the omeprazole concentration and the first derivative amplitude at 313 nm. The first derivative spectra was developed between 200 and 400 nm (deltalambda = 8). This method was validated and compared with the official high-performance liquid chromatography (HPLC) method of the USP. It showed good linearity in the range of concentrations studied (10-30 microg ml(-1)), precision (repeatability and inter-day reproducibility), recovery and specificity in stability studies. It also seemed to be 2.59 times more sensitive than the HPLC method. These results allowed to consider this procedure as useful for the rapid analysis of omeprazole in stability studies since there was no interference with its decomposition products.

Process-induced crystallite size and dissolution changes elucidated by a variety of analytical methods

The purpose of this work was the study, by multiple analytical techniques, of the physico-chemical changes and the dissolution behaviour of various recrystallized forms obtained through different recrystallization methods. Scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction and infra-red spectroscopy were applied to evaluate the samples. These analytical techniques showed changes in particle morphology, and ruled out the possibility of the existence of polymorphs, pseudopolymorphs, totally amorphous forms or chemical structural changes. The powder X-ray diffraction technique showed great reductions in the drug crystallite sizes induced by both recrystallization methods. The decreased drug crystallite sizes can explain the faster dissolution rates of the recrystallized samples as compared to the non-recrystallized drug acetylsalicylic acid (ASA), or to the physical mixtures of drug (ASA) and carrier (mannitol).

Comparison of assay methods by second-derivative spectroscopy, colorimetry and fluorescence spectroscopy of salicylic acid in aspirin preparations with a high-performance liquid chromatographic method

Second-derivative spectroscopy, colorimetry and fluorescence spectroscopy have been compared with a high-performance liquid chromatographic (HPLC) method for the assay of salicylic acid in preparations of aspirin. Results are presented for the linearity, sensitivity and reproducibility of these methods. The second-derivative spectroscopic and the HPLC methods were acceptable in terms of linearity, sensitivity and inter-day reproducibility and were convenient for the routine analysis of salicylic acid in aspirin preparations.