In-line monitoring of granule moisture in fluidized-bed dryers using microwave resonance technology.

This is the first report on in-line moisture measurement of pharmaceutical products by microwave resonance technology. In order to meet the FDA's PAT approach, a microwave resonance sensor appropriate for pharmaceutical use was developed and implemented into two different fluidized-bed dryers. The novel sensor enables a continuous moisture measurement independent from the product density. Hence, for the first time precise real time determination of the moisture in pharmaceutical granules becomes possible. The qualification of the newly developed sensor was performed by drying placebo granules under experimental conditions and the validation using drug loaded granules under real process conditions. The results of the investigations show good correlations between water content of the granules determined by the microwave resonance sensor and both reference methods, loss on drying by infrared light exposure and Karl Fischer titration. Furthermore, a considerable time saving in the drying process was achieved through monitoring the residual water content continuously by microwave resonance technology instead of the formerly used discontinuous methods.

Pediatric drug formulations of sodium benzoate: II. Coated granules with a lipophilic binder.

Sodium benzoate is used as a therapeutic agent in the treatment of some rare disorders that predominantly affect children. In preliminary investigations, liquid and semi-solid formulations of sodium benzoate failed because children refuse the oral uptake due to the bad taste of the drug. Recently developed microcapsules with macrogol as a hydrophilic binder raise concern in high-dose treatment regimens because acceptable daily intake limits are exceeded. A novel microcapsule formulation was developed consisting of a lipophilic core with high sodium benzoate load and a saliva-resistant coating. A new powder quality of saturated triglycerides from plant origin was introduced which complies with the Ph. Eur. monograph 'Hard fat'. Sodium benzoate and the triglyceride were mixed and directly extruded at room temperature. The extrudates were spheronized and coated in a fluidized-bed process. The resulting coated granules are small-sized microcapsules and taste neutrally. They can be mixed with food before administration. As the amount of released sodium benzoate is negligible within the first minutes, children do not recognize the bad taste and accept the medication. Recently, sodium benzoate in this novel formulation has been designated by the European Community as an orphan drug in the treatment of non-ketotic hyperglycinemia.