Santiago Torrado

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.

Gelatinized/freeze-dried starch as excipient in sustained release tablets

Abstract Recently starch has been studied as a forming-matrix excipient for sustained oral dosage forms. We are studying a new technique for the production of cold water-swellable starch using gelatinization and freeze-drying processes, and the product obtained has been characterized. We made matrices containing different modified starch-hydroxypropyl methylcellulose mixtures and studied their possible erosion-diffusion mechanism and release rate in dissolution tests which was found to be similar to that of the HPMC matrix.

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%).

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.

Methimazole-mediated enhancement of albendazole oral bioavailability and anthelmintic effects against parenteral stages of Trichinella spiralis in mice: the influence of the dose-regime

The influence of methimazole (MTZ) inhibitor of the microsomal oxidases on the systemic availability of the albendazole sulpho-metabolites (ABZS-MT) albendazole-sulphoxide (ABZSO) and albendazole-sulphone (ABZSO2) and on its anthelmintic effects was investigated in a mouse model for helminthic infections. Plasma concentrations of the ABZS-MT were measured by high performance liquid chromatography (HPLC) following treatment of Swiss CD-1 mice with albendazole (ABZ) alone or ABZ plus MTZ, at both single and repeated doses. The anthelmintic effects were assessed in age-matched mice similarly treated following infection with Trichinella spiralis. MTZ significantly (p < 0.01) increased the ABZS-MT plasma concentrations although the pharmacokinetic profile varied greatly according to the dose of ABZ administered. When ABZ was given at a single dose of 50 mg/kg followed by MTZ at 3 mg/kg, a cumulative effect was observed in the ABZS-MT plasma levels with pharmacokinetic parameters (Tmax = 24 h, Cmax= 30.88 microg/ml and AUC = 1120.80 microg h/ml) significantly ( p < 0.01) higher than those following administration of ABZ alone (Tmax = 3 h, Cmax = 11.00 microg/ml and AUC = 268.03 microg h/ml). This cumulative effect was absent following administration of ABZ at 100 mg/kg where, after reaching a maximum (Cmax = 27.23 microg/ml) at 3 h post-administration (Tmax), the ABZS-MTplasma levels felt down quickly to values under those obtained after administration of ABZ at the same dose, but alone (AUC = 362.15 microg h/ml vs. 340.15 microg h/ml, respectively). When ABZ was given at 50 mg/kg together with MTZ three times every 24 h, a rapid decrease was observed in the ABZS-MT plasma levels following administration of both the second and third doses, respectively. The pharmacokinetic profile of ABZS-MT following administration of each of the three doses of ABZ at 100 mg/kg plus MTZ was the same as that obtained after the single treatment. The rapid decrease of the ABZS-MT plasma levels observed after the sustained treatment or after the single treatment at 100 mg/kg could be due to a microsomal oxidase inductive effect (probably the cytochrome P-450) caused by ABZSO. The co-administration of MTZ significantly (p < 0.01) increased the anthelmintic effects of ABZ against both migrating and encysted larvae of T. spiralis. Repeated treatment did not improve the anthelmintic effects of the single treatment as the efficacies against both stages of the parasite were always lower or identical to those of the single treatment at the corresponding doses.

Formulation parameters of albendazole solution

Abstract The solubility of albendazole, a poorly water-soluble drug was evaluated. The effect of cosolvents and pH on the aqueous solubility of albendazole are described here. Albendazole aqueous solubility was tested over the pH range of 1.2–7.5. Albendazole solubility was lower for the highest pH values. The solubility coefficient obtained was 0.376 mg/ml in a 1.2 pH buffer solution. Transcutol was the cosolvent with which the increase of the solubility was highest. Albendazole solubility at different percentages of transcutol presented a sigmoid kinetic with an initial acceleration phase. This kinetic shows an exponential correlation for transcutol values smaller than 80%). The exponent value (n) was higher as the pH of the solution was increased. This high value of the exponent (n) is due to a stronger influence of the transcutol on the solubility of albendazole at elevated pH values. The albendazole solution containing 40% w/w of transcutol in a pH 1.2 buffer solution was selected because of its high solubility (2.226 mg/ml). Analysis of the stability data of this albendazole solution showed good correlation ( r = 0.9831) when the data were fitted to a first order equation. This albendazole solution showed good stability, with less than 10%, degradation occurring after 30 days of storage at 4°C.

Quantitative determination of dimethicone in commercial tablets and capsules by Fourier transform infrared spectroscopy and antifoaming activity test

Fourier transform infrared (FTIR) spectroscopy and antifoaming activity test have been employed for the quantitative analysis of dimethicone. Linearity, accuracy and precision are presented for both methods. These methods have been also used to compare different dimethicone-containing proprietary medicines. FTIR spectroscopy has shown to be adequate for quantitation of dimethicone in commercial tablets and capsules in order to comply with USP requirements. The antifoaming activity test is able to detect incompatibilities between dimethicone and other constituents. The presence of certain enzymes in some medicinal products increases the defoaming properties of these formulations.