Rafael Cadórniga

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.

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 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.

Preparation, characterization and dissolution of ciprofloxacin/PEG 6000 binary systems

Abstract Thermomicroscopy and DSC were employed to study ciprofloxacin/PEG 6000 binary systems in the form of solid dispersions and physical mixtures. The dissolution processes of ciprofloxacin from the binary systems and pure ciprofloxacin were also studied.

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.

Compression Behavior of Acetylsalicylic Acid Pellets

AbstractAn instrumented tablet press was used to study the compression behavior of different acetylsalicylic acid (AAS) formulations. Formulations of AAS crystals and uncoated AAS pellets have compression behavior similar to formulations of AAS pellets coated with acrylic resins (Eudragit RS) and mixed with a 20% of microcrystalline cellulose. Formulations of AAS coated pellets without any excipient exhibited a more plastic compression behavior then the other formulations. Matrix tablets of AAS were produced by compression of formulations of AAS coated pellets without any excipients.The drug release profile of the pellets before and after compression was also studied. Microcrystalline cellulose concentrations higher than 15% w/w were required to obtain tablets of coated pellets with drug release profiles similar to the coated pellets before compression. It can be concluded from the present work that compression data of coated particles can be useful to study the possible damage of the film coat of the par...

Stereoselective drug release from Ketoprofen and Ricobendazole matrix tablets

Crystalline characteristics of racemic, pure R and S enantiomers and physical mixtures of Ketoprofen (KET) have been studied by DSC and X-ray diffractometry. Aqueous solubilities were 182.6 +/- 9.1 microg/ml for racemic KET, 259.6 +/- 6.6 microg/ml for R-KET, and 304.3 +/- 2.7 microg/ml for S-KET. Matrix tablets made with racemic and physical mixtures of KET show stereoselective drug release, which is faster for S-KET than for R-KET. This effect is more marked when the chiral excipient hydroxypropylmethylcellulose (HPMC) is used in place of the achiral Eudragit RL. Stereoselectivity of release is also affected by the amount of KET. Similar results were obtained when another chiral drug with low solubility, Ricobendazole (RBZ), is used. Depending on the excipient and drug dosage, more or less marked stereoselective drug release is obtained in RBZ matrix tablet formulations.

Topical application of albumin microspheres containing vitamin A : drug release and availability

Abstract Egg albumin microspheres containing vitamin A (15.7 ± 0.8% w/w; size 222 ± 25 μm) were produced by an emulsion method. These particles were used to prepare O/W creams of vitamin A. The in vitro and in vivo drug release of a microencapsulated vitamin A cream was studied and compared with a non-microencapsulated vitamin A cream. The in vivo study in six volunteers shows that these microspheres were able to remain on the skin for a long period of time, and as a consequence they were able to prolong the release of vitamin A. The relative availability of the microencapsulated vitamin A cream, compared with the non-microencapsulated vitamin A cream was 78.2 ± 7.3%.

Effect of drug release rate on bioavailability of different aspirin tablets

The relationship between in vitro dissolution and in vivo characteristics of acetylsalicylic acid (ASA) from six different types of sustained-release tablet was evaluated. ASA pellets coated by Eudragit RS or L were tableted with different proportions of microcrystalline cellulose 0 or 25% (w/w). The ASA release rate from these tablets was adjusted to the Higuchi and Peppas equations. When microcrystalline cellulose was used at 25%, a faster disintegration time was obtained than when it was not used. The slope of the Higuchi plots of the microcrystalline cellulose formulation were always higher than the formulations without microcrystalline cellulose (matrix tablets). In the Peppas equation, the n values were higher for tablets containing Eudragit RS than for the tablets containing Eudragit L. The bioavailability of six different formulations were assayed in volunteers by urinary excretion data. Bioavailability was related to the dissolution release rate. Formulations with faster drug release rate showed higher bioavailability. Only the slowest formulations had a reduced bioavailability.

A Selective Liquid Chromatography Assay for the Determination of d1-α-Tocopherol Acetate in Plasma Samples

Abstract A high-performance liquid chromatographic (HPLC) method for the assay of tocopherol and tocopherol acetate in biological samples is described. Results was presented for the linearity, sensitivity and reproducibility. This HPLC method for tocopherol acetate was acceptable in terms of linearity, sensitivity and inter-day reproducibility and was convenient for the routine analysis of plasma samples.