minocycline and stearic-acid

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.

Topics: Anti-Bacterial Agents; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Drug Liberation; Lipids; Minocycline; Periodontitis; Plasticizers; Polyesters; Polyethylene Glycols; Stearic Acids

The objective of this study was to develop an improved drug delivery system for the local antimicrobial treatment of periodontitis, that offers enhanced drug stability, easy application and controlled release over several weeks. Chelate complexes consisting of a tetracycline antibiotic and a fatty acid salt were developed. Minocycline and doxycycline were paired with magnesium- and calcium stearate in different molar ratios. These chelate complexes stabilize the active pharmaceutical ingredient and enable the incorporation into a PLGA (poly(lactic-co-glycolic acid)) polymer matrix via hot melt extrusion. The chelate complexes were characterized via UV/Vis- and IR-spectroscopy. A high antibiotic activity of the complex was observed in a disc diffusion test. The drug complex was mixed with different PLGA-polymers and cryomilled in advance of the extrusion. The hot melt extrusion yielded homogeneous extrudates with a diameter from 600 to 900 µm. They contain 11.5% of minocycline, are adjustable in length and are easy to handle. In vitro release studies revealed a controlled release of the drug over 42 days. In conclusion, the developed extrudates are promising systems to improve the treatment of periodontitis.

Topics: Anti-Bacterial Agents; Delayed-Action Preparations; Doxycycline; Drug Carriers; Drug Compounding; Drug Liberation; Drug Stability; Kinetics; Minocycline; Particle Size; Periodontitis; Polylactic Acid-Polyglycolic Acid Copolymer; Staphylococcus aureus; Stearic Acids