The effect of particle size on the sublimation behavior of butylhydroxytoluene as antioxidant in tablets during storage and coating.

The effect of particle size on the sublimation behavior of butylhydroxytoluene (BHT) was investigated when BHT was included as antioxidant in tablets. Sublimation of pure BHT was found to be independent of its particle size, with pore formation on the surface of all tablets after storage at room temperature and above. Moreover, a higher residual BHT content after storage was detected in tablets containing a larger size fraction. X-ray µCT scans revealed the formation of peripherally larger pores at higher BHT particle sizes, implying a slower sublimation rate in the tablet core. A stability study indicated an increase in the extent of BHT sublimation at higher temperature and longer exposure time for all size fractions. The influence of BHT particle size was more pronounced when the tablets were stored at higher temperature, but the effect receded with longer exposure time. Similar trends were seen in film-coated tablets. Due to the short exposure time to elevated temperatures, a gradient in pore size was also observed at smaller particle sizes, with peripheral pores being larger in uncoated tablets. Superficial pores disappeared when a film coating was deposited onto the tablets. After storage of the film-coated tablets, less BHT had sublimated compared to the uncoated tablet. The coating layer did not prevent sublimation, but the process was slowed down.

Development of a new age-appropriate, chewable tablet of mebendazole 500 mg for preventive chemotherapy of soil-transmitted helminth infections in pre-school and school-age children.

The aim of this study was to develop an age-appropriate tablet of mebendazole 500 mg to be used in large donation programs by the World Health Organization (WHO) for preventive chemotherapy of soil-transmitted helminth (STH) infections in pre-school and school-age children living in tropical and subtropical endemic areas. To that end, a new oral tablet formulation was developed that can be either chewed or given to young (≥1 year old) children by spoon after rapid disintegration to a soft mass with the addition of a small amount of water directly on the spoon. Although the tablet was manufactured using conventional fluid bed granulation, screening, blending, and compression processes, one of the main challenges was to combine properties of a chewable, dispersible, and regular (solid) immediate release tablet to meet the predefined requirements. The tablet disintegration time was below 120 s, allowing for administration by the "spoon method". The tablet hardness was higher (160-220 N) than normally applicable for chewable tablets, permitting shipment along a lengthy supply chain in a primary 200-tablet count bottle packaging. In addition, the resulting tablets are stable for 48 months in all climatic zones (I-IV). In this article, several aspects of the development of this unique tablet are described, including formulation, process development, stability, clinical acceptability testing, and regulatory filing.