Controlled release minocycline-lipid-complex extrudates for the therapy of periodontitis with enhanced flexibility

Int J Pharm. 2020 Aug 30;586:119578. doi: 10.1016/j.ijpharm.2020.119578. Epub 2020 Jun 30.

Abstract

We describe the development of flexible minocycline-lipid-complex extrudates with optimized mechanical and drug release properties. These extrudates contain a minocycline - magnesium stearate chelate complex with a higher stability in aqueous media, which has now been incorporated in a PEG-PLGA (polyethylene glycol - poly(lactic-co-glycolic acid)) matrix. PEG 1500 has been utilized in different concentrations to serve as plasticizer. The novel formulations have been characterized by texture analysis, X-Ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Extrudates with a reduced diameter of 300 µm (previously 600 µm) were introduced, and a more sensitive quantification method with a tandem-mass spectrometry detector was developed. From all tested formulations, the extrudates consisting of Expansorb DLG 50 - 6P (PEG-PLGA, molar weight 30-60 kDa) paired with 10% PEG 1500 emerged as best formulation. These extrudates feature a drug content of 11.5% and a controlled release over at least 42 days. The release profile is without a lag time and shows initially a slightly higher release rate, which is desired. Compared to previous developments, the extrudates now offer a high flexibility combined with a large mechanical resilience, which will ease the handling and administration.

Keywords: Complex; Controlled Release; Extrusion; Minocycline; PEG-PLGA; Periodontitis.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / chemistry
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Drug Carriers / chemistry
  • Drug Liberation
  • Lipids / chemistry*
  • Minocycline / administration & dosage*
  • Minocycline / chemistry
  • Periodontitis / drug therapy
  • Plasticizers / chemistry
  • Polyesters / chemistry*
  • Polyethylene Glycols / chemistry*
  • Stearic Acids / chemistry

Substances

  • Anti-Bacterial Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Lipids
  • Plasticizers
  • Polyesters
  • Stearic Acids
  • polyethylene glycol-poly(lactide-co-glycolide)
  • Polyethylene Glycols
  • stearic acid
  • Minocycline