Design and development of a combined calcium-iron-folic acid prenatal supplement to support implementation of the new World Health Organization recommendations for calcium supplementation during pregnancy.

BACKGROUND: Hypertensive diseases of pregnancy are important causes of maternal and perinatal mortality. Based on meta-analyses of efficacy trials of prenatal calcium supplementation to reduce the risk of hypertensive diseases of pregnancy, the World Health Organization recommends 1.5 to 2.0 g of elemental calcium per day for pregnant women with low dietary calcium intakes (as well as 60 mg of iron and 400 microg of folic acid). However, implementation of this recommendation is challenged by the size and number of calcium tablets required and the need to avoid concurrent ingestion of calcium and iron due to intraintestinal interactions. OBJECTIVE: We developed a novel micronutrient powder containing microencapsulated pH-sensitive calcium in addition to iron and folic acid, designed to facilitate early intestinal iron release and delayed calcium release. METHODS: Two pharmaceutical companies were contracted to develop a prototype, one of which was chosen for clinical testing. Calcium carbonate granules were coated with a trilayer pH-sensitive enteric coating using a fluid-bed spray coater. Iron and folic acid granules were encapsulated with a time-release coating. Iron and calcium dissolution profiles were assessed during exposure to acidic (pH 1.2) and/or basic (pH 5.8) media using a modified USP apparatus 1 (basket) method. RESULTS: At pH 1.2, calcium and iron release was < or = 10% and > 90% after 120 minutes, respectively. At pH 5.8, > 80% of total calcium was released after 90 minutes. CONCLUSIONS: Based on in vitro criteria, the supplement may be a promising approach for delivering calcium, iron, and folic acid as a single daily dose to pregnant women in settings of low dietary intake of calcium.

A combination of pH-sensitive caplet coatings may be an effective noninvasive strategy to deliver bioactive substances, nutrients, or their precursors to the colon.

We hypothesize that bacterially synthesized nutrients in the large intestine may significantly influence the nutritional status of humans and, specifically, that of the colonocytes. In vivo research with human subjects in this area has been extremely limited because of the absence of a noninvasive means to quantitatively deliver test doses of nutrients, or their precursors, to the colon. The purpose of this study was to design and test the effectiveness of a pH-dependent coating in delivering intact placebo caplets to the large intestine. Barium sulphate caplet cores (19.1 mm x 9.7 mm) were coated with 2 different pH-dependent acrylic copolymer products, Eudragit L100 and S100, in either a 1:0 ratio (100% Eudragit L100) or 3:1 ratio (75% Eudragit L100 and 25% S100). The disintegration profile of each formulation was determined through in vitro testing, then caplets were sequentially administered to 10 healthy volunteers, and monitored in vivo via serial abdominal fluoroscopic images. Test caplets with the 3:1 coating formulation had a 40% higher colon-targeting specificity compared with the 1:0-coated caplets, and tended to begin disintegrating at a later time after administration (p = 0.09). The total time from administration to complete disintegration was also significantly longer for the 3:1-coated caplets (p = 0.003). These results suggest that barium sulphate caplets with a 3:1 acrylic copolymer coating formulation ratio (Eudragit L100 and S100) may be a suitable delivery system for quantifying the biosynthesis of nutrients in the human large intestine and measuring their absorption across the colonic epithelium.

Development and application of a novel UV method for the analysis of ascorbic acid.

A UV method for the analysis of ascorbic acid with methanol as solvent to prepare a sample has been developed and applied. The effect of copper(II) concentrations on the oxidation of ascorbic acid in aqueous solution has been studied in detail, and the regularities of ascorbic acid oxidation in methanol, USP phosphate buffer (pH 2.50) and de-ionized water have been found. Upon experiments ascorbic acid has been found to dissolve in methanol, and its solubility in it has been measured to be 81.0mg/ml at room temperature (22 degrees C). The ascorbic acid bulk material from a manufacturer has been assayed to be 89.34% with this method, in good agreement with the assay value (89.58%) from the titration method. The ascorbic acid granule and tablet content uniformity also has been tested using this method. This method is simple, rapid, accurate and reliable, and can be adopted for the routine determination of ascorbic acid in its granule and tablet formulations.