Studies of wet granulation in small scale high shear mixer of 20 mg tablets of policosanol.

It was studied the influence of three factors in the manufacturing process of tablets containing 20 mg of policosanol in a small scale when was used a high shear mixer. A factorial design without repetitions was used, considering as independent variables: volume of binder solution, kneading time and the use or not of chopper. Data analysis was carried out using the Yates algorithm, considering the effect of these three factors over the diameter of the granules, the percent of fine powders in granulate and the compression forces. The diameter of the granules was increased with an increase in the volume of the binder solution added and with an increase in the kneading time and was decreased when the chopper was used. The percent of fine powders, present in granulate, was significantly diminished with an increase of the volume of binder solution and diminished with an increase in the kneading time, the influence of the use of chopper was insignificant. The compression forces diminished with the use of chopper, with the increase of the volume of binder solution used and are not affected with the changes in the kneading time.

Study of the interaction between policosanol and excipients.

Policosanol is an active principle, composed by 8 fatty alcohols: 1tetracosanol, 1-hexacosanol, 1-heptacosanol, 1-octacosanol, 1-nonacosanol, 1-triacontanol, 1-dotriacontanol and 1-tetratriacontanol that shows a very stable, well defined and reproducible composition from batch to batch that is analysed using gas chromatography. Continuing the studies of the compatibility among policosanol and different tablet excipients, it was studied if the mixtures of those excipients with policosanol produce chemical interactions between them, the samples were analysed using gas chromatography and was determined if it was affected the content of policosanol in them. When all the samples were analysed, no changes in the policosanol content of the samples were observed, and it was considered that no interactions are produced in any of the mixtures policosanol/excipients under study.

Study of the stability of tablets containing 10 mg of policosanol as active principle.

The stability studies of tablets containing 10 mg of policosanol, a new cholesterol lowering drug, were conducted to predict an expiration date and to search the appearance of putative degradation products. All quality specification parameters such as colour, moisture content, hardness, disintegration, policosanol content and microbiological limits of the tablets were done. The effect of drastic treatments such as acid and basic hydrolysis, oxidative and photolytic degradation as well as thermolysis on such parameters was studied. In addition; studies under drastic conditions of storage (40 degrees C and 75% R.H.) and under ambient conditions of storage for climatic zones II and IV were performed. These studies demonstrate that these tablets are a stable pharmaceutical formulation, without significant changes on their quality criteria at the stressed conditions studied. The chromatographic profile of the samples after 9 months of thermal degradation shows chromatographic peaks that corresponds to the octacosanoyl, triacontanoyl and hexacosanoyl esters of palmitate and stearate, being the only degradation products observed on these studies.

Stability studies of tablets containing 5 mg of policosanol.

The stability studies of tablets containing 5 mg of policosanol, a new cholesterol lowering drug, were conducted to predict an expiration date and to search the appearance of putative degradation products. All quality parameters such as colour, moisture content, hardness, disintegration, policosanol content and microbiological limits of the tablets were assessed. The effect of extreme treatments such as acid and basic hydrolysis, oxidative and photolytic degradation as well as thermal degradation, on the policosanol content was studied. In addition, studies under extreme conditions of storage [(40 +/- 2) degree C and (75 +/- 5)% R.H.] as well as 37, 45, 55 and 60 degrees C combined with 50, 75 and 92% R.H.) and under ambient conditions of storage for climatic zones II and IV were performed. These studies demonstrate that these tablets are a stable pharmaceutical formulation, without significant changes in their quality criteria at the stressed conditions used, so that policosanol content remains unchanged during the entire studies. The chromatographic profile of the samples after 9 months of thermal degradation shows chromatographic peaks that corresponds to the palmitate and stearate esters of octacosanoyl, triacontanoyl and hexacosanoyl, being the only degradation products observed on these studies.

Formulation in tablets of a cholera whole cells inactivated vaccine candidate.

Licensed as well as candidate cholera vaccines available at the present requires the dose preparation (included buffer) at the moment of application. The aim of this work was to evaluate the presentation in oral tablets of an inactivated cholera vaccine to avoid that inconveniences during application. We have therefore compared inactivated cultures of Vibrio cholerae with tablets formulation vaccine. We obtained that antigenic activity (ELISA) and immunogenicity in animal model (ELISA and vibriocidal tests) of V. cholerae inactivated cell remained unaltered in the final tablet formulation. The results suggest that the oral tablet formulation could be a useful pharmaceutical form in order to produce a new and affordable cholera vaccine.

Physico-mechanical characterization of policosanol, a novel hypocholesterolemic drug.

As part of the formulation studies of policosanol, a new hypocholesterolemic drug, a physico-mechanical characterization was developed. Thermal analysis, using differential scanning calorimetry was used to evaluate the purity of policosanol from batch to batch and, also, the particle size distribution. The degree of wettability of policosanol was studied by measuring the contact angle and solubility in different solvents. The compressibility and cohesion of particles were evaluated using a profile of compression forces, ranging between 6.5 kN and 39.0 kN. Also, other properties such as flow properties, true density, and tapped and bulk density were measured. The industrial batches of policosanol that were studied show an adequate purity and a uniform distribution of the particle sizes. Policosanol shows good flow properties, compressibility, and cohesion as well as a low solubility in the majority of the solvents used in the pharmaceutical industry, and its solubility in water or in aqueous solutions was, mainly, null. The wettability of policosanol in the different solvents shows the following order: methylene chloride > ethanol > acetone >> water.