Enteric-coated alendronate sodium nanoliposomes: a novel formula to overcome barriers for the treatment of osteoporosis

Expert Opin Drug Deliv. 2013 Jun;10(6):741-6. doi: 10.1517/17425247.2013.799136. Epub 2013 May 8.

Abstract

Background and objectives: Alendronate sodium (ALS) is the most common drug used for the treatment of osteoporosis. The challenges facing ALS use include: very poor oral bioavailability (0.6%), esophageal ulcers, and complicated instructions for its use. The objective of this research is to utilize nanotechnology to formulate ALS into enteric-coated nanoliposomes (NLS) to overcome the previously mentioned drawbacks.

Methods: NLS were prepared with lipid components of phosphatidylcholine (PC), cholesterol (CH), and lecithin (Lec) in ratios 4:1:1, 4:2:1, 4:3:1, and 4:4:1, respectively. Formulas that showed the highest entrapment efficiency were prepared either alone or mixed with positive and negative charge-inducing agents and coated with Eudragit L100. Eudragit-coated NLS (EuC-NLS) were evaluated for particle size, zeta potential, morphological examination, and drug release in pH 1.2 and pH 7.4 media. The pharmacokinetic study was carried out in rabbits.

Results: Spherical NLS were successfully developed with a mean size range from 70 to 150 nm. EuC-NLS with PC:CH:Lec:dicetyl phosphate (4:3:1:1) successfully resist the release of ALS in acidic environments and enhanced the bioavailability in rabbits 12-fold compared with the marketed tablets.

Conclusions: EuC-NLS is a promising novel formula for ALS with higher bioavailability and a lower dose, avoiding the side effects of esophageal ulceration.

MeSH terms

  • Alendronate / chemistry
  • Alendronate / pharmacokinetics*
  • Animals
  • Biological Availability
  • Bone Density Conservation Agents / chemistry
  • Bone Density Conservation Agents / pharmacokinetics*
  • Chemistry, Pharmaceutical
  • Coated Materials, Biocompatible / chemistry*
  • Drug Delivery Systems*
  • Hydrogen-Ion Concentration
  • Intestinal Absorption
  • Intestinal Mucosa / metabolism
  • Liposomes
  • Male
  • Osteoporosis / drug therapy*
  • Particle Size
  • Polymethacrylic Acids / chemistry*
  • Rabbits

Substances

  • Bone Density Conservation Agents
  • Coated Materials, Biocompatible
  • Liposomes
  • Polymethacrylic Acids
  • methylmethacrylate-methacrylic acid copolymer
  • Alendronate