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.

The Future of CMC Regulatory Submissions: Streamlining Activities Using Structured Content and Data Management.

Recent advancements in data engineering, data science, and secure cloud storage can transform the current state of global Chemistry, Manufacturing, and Controls (CMC) regulatory activities to automated online digital processes. Modernizing regulatory activities will facilitate simultaneous global submissions and concurrent collaborative reviews, significantly reducing global licensing timelines and variability in globally registered product details. This article describes advancements made within the pharmaceutical industry from theoretical concepts to utilization of structured content and data in CMC submissions. The term Structured Content and Data Management (SCDM) outlines the end-to-end scientific data lifecycle from capture in source systems, aggregation into a consolidated repository, and transformation into semantically structured blocks with metadata defining relationships between scientific data and business contexts. Automation of regulatory authoring (termed Structured Content Authoring) is feasible because SCDM makes data both human and machine readable. It will offer health authorities access to the digital data beyond the current standard of PDF documents and, for a review process, SCDM would "enrich the effectiveness, efficiency, and consistency of regulatory quality oversight" (Yu et al., 2019). SCDM is a novel solution for content and data management in regulatory submissions and can enable faster access to critical therapies worldwide.

Retention and selectivity of stationary phases for hydrophilic interaction chromatography.

More and more polar stationary phases have become available for the separation of small polar compounds in the past decade as hydrophilic interaction chromatography (HILIC) continues to find applications in new fields (e.g., metabolomics and proteomics). Bare silica phases remain popular, especially in the bio-analytical area. A wide range of functional groups (e.g., amino, amide, diol, sulfobetaine, and triazole) have been employed as polar stationary phases for HILIC separation. This review provides a survey of the popular stationary phases commercially available and discusses the retention and selectivity characteristics of the polar stationary phases in HILIC. The purpose of the review is not to provide a comprehensive overview of literature reports, but rather focuses on findings that demonstrate retention and selectivity of the polar stationary phases in HILIC.

Retention behavior of small polar compounds on polar stationary phases in hydrophilic interaction chromatography.

Retention characteristics of four polar stationary phases (i.e., amide, amino, silica and sulfobetaine) were studied by using a group of small polar compounds in hydrophilic interaction chromatography (HILIC). Different polar stationary phases shared certain degrees of similarity, but also exhibited differences in retentivity and selectivity for the model compounds. Among the four columns studied, HILIC Silica column had the least retention for the model compounds, but also showed different selectivity from other three columns. Experimental data also provided some evidences that functional groups on the stationary phases might have certain degrees of influence on selectivity possibly through secondary interactions with the model compounds. The retention of the acids on the amino phase decreased with increasing salt concentration in the mobile phase due to the ion-exchange effect, and the retention process was endothermic as opposed to exothermic on other phases. This study also systematically investigated the effect of various experimental factors on the retention of the polar stationary phases, such as acetonitrile content, column temperature, buffer pH, salt type and concentration in the mobile phase.