title: 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.
abstract: 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.
authors: Ashley M
authors: AM
authors: Aimone Phillips
authors: Stanley H
authors: SH
authors: Zlotkin
authors: Jo-Anna B
authors: JA
authors: Baxter
authors: Frank
authors: F
authors: Martinuzzi
authors: Tanush
authors: T
authors: Kadria
authors: Daniel E
authors: DE
authors: Roth
mesh_terms: D002136:Calcium, Dietary / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019587:Dietary Supplements; D004339:Drug Compounding / Q000379:methods; D004347:Drug Interactions; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D019266:Iron, Dietary / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018673:Nutrition Policy; D011247:Pregnancy; D011295:Prenatal Care / Q000379:methods*; D014944:World Health Organization
chemical_list: D002136:Calcium, Dietary; D019266:Iron, Dietary; D005492:Folic Acid