Pharmacotechnological pitfalls of priming--possible source of microembolization during open heart surgery.

OBJECTIVES: Besides low mortality and morbidity rates in cardiac surgery, the associated cognitive dysfunction is the focus of interest. One possible reason is microembolisation. METHODS AND RESULTS: The authors analysed the crystallogenesis in the calcium-containing prime, inspired by their observation that the fluid sometimes becomes turbid during the priming process. Lactated Ringer-based prime solutions were tested, adding mannitol, NaHCO(3), and heparin. The oxygenator was ventilated with compressed medical air. Samples were taken for dynamic light scattering particulate level analysis. The priming was furthermore modelled in the laboratory by mixing the components and then ventilating the mixture through with compressed air. Turbid solutions from the operating room contained 100-6500 nm crystals, while clear solutions contained 20-473 nm particles. In the model, continuous pH measurement showed pH 6.4-7.4 after blending the solutions, which then elevated the pH to 7.5-8.0 after ventilation with concomitant turbidity. The pH of the prime can be stabilized by the addition of ascorbic acid (1-2 mg/ml) and, also, the turbidity may be prevented. CONCLUSION: Ventilating the lactated Ringer-based calcium-containing primes after blending is not advisible because of alkalization and crystallogenesis. Ascorbic acid stabilizes the pH and prevents crystallogenesis in the prime. Pre-bypass filtration is recommended.

Investigation on drug dissolution and particle characteristics of pellets related to manufacturing process variables of high-shear granulation.

There is a growing interest for multiparticulate solid dosage forms such as pellets, because of their several advantages over tablets during drug therapy. It is essential to investigate the drug dissolution process which can be influenced by the composition and manufacturing process technology, too. This study was performed applying experimental design in order to evaluate the effects of independent process variables during high-shear pelletisation, taking the impeller speed (x1) and granulation binder flow rate (x2) as factors into consideration. Theophylline containing pellet formulation was prepared using a matrix consisted of ethylcellulose, microcrystalline cellulose and lactose. Dissolution profiles were modeled by the Weibull function to evaluate the power of process variables. Both process variables were powerful to influence the particle agglomeration. A linear regression was found between the particle size and the diffuse reflectance values after the Kubelka-Munk transformation. Differences in the diffuse reflectance spectra of pellet samples related to particle size offer a fast instrumental method for the in-process control.

[Particle size determination using the method of dynamic light scattering]. / Részecskeméret-meghatározás a dinamikus fényszóródás módszerével.

Realising the lacks of the classic methods of particle size determination a new method was needed to be developed which became suitable for measurements in the nano range as well. The principle of this method was discovered more than 20 years ago but manufacturers are still able to insert novelties by developing and refining the technique of - dynamic light scattering. Importance of multiparticular systems increases in pharmaceutical technology. It is necessary to apply this new method to investigate them.