Iron(II) sulfate release from drop-formed lipophilic matrices developed by special hot-melt technology

• Published in: European journal of pharmaceutics and biopharmaceutics 2004-03, Vol.57 (2), p.287-294
• Main Authors: Pallagi, E, Vass, K, Pintye-Hódi, K, Kása, P, Falkay, G, Erős, I, Szabó-Révész, P
• Format: Article
• Language: English
• Subjects: Animals; Chemistry, Pharmaceutical; Gastric mucosa irritation; Hot-melt technology; Iron - chemistry; Iron - pharmacokinetics; Iron(II) sulfate; Lipids - chemical synthesis; Lipids - pharmacokinetics; Lipophilic matrix; Particle Size; Rabbits; Sulfates - chemical synthesis; Sulfates - pharmacokinetics; Sustained release, in vitro dissolution, in vivo experiment; Technology, Pharmaceutical - methods
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2003.10.017

Iron(II) sulfate-containing lipophilic matrices were developed by a special hot-melt technology (melt solidification in drops), using stearin, white wax and their mixture as conventional bed materials. The special technology resulted in spherical particles which can be filled directly into capsules; these store iron as a depot and ensure a slow and uniform release, whereby the irritation of the gastric mucosa by the iron can be decreased. The rates of dissolution of the iron(II) sulfate from the various lipophilic matrices were different, but fundamentally low. Kinetic calculations demonstrated that the rate of dissolution of the iron(II) sulfate was of approximately zero kinetic order. The results of in vivo experiments on rabbits correlated well with the in vitro data. The plasma curves for the animals treated with the iron(II) sulfate preparations varied with the excipients in the depot products. The properties and ratio of the bed materials influenced the release of the iron(II) sulfate. In all probability, the release of the active agent can be regulated through the use of a melt of stearin and white wax in different ratios. The development products functioned as a sustained-release system and ensured elimination of the irritation of the gastric mucosa. At the same time, the results justified the applicability of the special hot-melt technology in the development of the solid dosage form.