Strategies to Stabilize Dalbavancin in Aqueous Solutions; Section-2: The Effects of 2 Hydroxypropyl-β-Cyclodextrin and Acetate Buffer with and Without Divalent Metal Ions.

The effect of 2-hydroxpropyl-β-cyclodextrin (2HPβCD) with or without divalent metal ions (Ca, Mg, and Zn) on the stability of dalbavancin in acetate buffer was investigated. Dalbavancin recovery from formulations with 2HPβCD and divalent metal ions after four weeks of storage at 5 °C and 55 °C was measured by RP-HPLC and HP-SEC; a longer-term study was carried out over six months at 5 °C, 25 °C, and 40 °C. Binding of 2HPβCD was characterized by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR).

Strategies to Stabilize Dalbavancin in Aqueous Solutions; Section-1: the Effects of Metal Ions and Buffers.

Purpose: The effect of monovalent (Na and K) and divalent (Ca, Mg, and Zn) metal ions combined with citrate or acetate buffers (pH 4.5) on the stability of dalbavancin in aqueous solutions was investigated.

Method: RP-HPLC and HP-SEC were used to evaluate the stability of aqueous solutions of dalbavancin in different combinations of buffers and metal ions after four weeks of storage at 5°C and 55°C.

Strategies To Stabilize Dalbavancin in Aqueous Solutions; Section 3: The Effects of 2 Hydroxypropyl-β-Cyclodextrin and Phosphate Buffer with and without Divalent Metal Ions.

Purpose: New formulations of the glycopeptide drug dalbavancin containing 2-hydroxpropyl-β-cyclodextrin (2HPβCD) with or without divalent metal ions in phosphate buffer (pH 7.0) were tested to evaluate whether these excipients influence the aqueous solution stability of dalbavancin.

Method: Recovery of dalbavancin from phosphate buffered solutions at pH 7.

A Systematic Degradation Kinetics Study of Dalbavancin Hydrochloride Injection Solutions.

The degradation kinetics of the glycopeptide antibiotic dalbavancin in solution are systematically evaluated over the pH range 1-12 at 70°C. The decomposition rate of dalbavancin was measured as a function of pH, buffer composition, temperature, ionic strength, and drug concentration. A pH-rate profile was constructed using pseudo first-order kinetics at 70°C after correcting for buffer effects; the observed pH-rate profile could be fitted with standard pseudo first order rate laws.

Glycopeptide antibiotic drug stability in aqueous solution.

Glycopeptide antimicrobials are a class of naturally occurring or semi-synthetic glycosylated products that have shown antibacterial activity against gram-positive organisms by inhibiting cell-wall synthesis. In most cases, these drugs are prepared in dry powder (lyophilized) form due to chemical and physical instability in aqueous solution; however, from an economic and practical point of view, liquid formulations are preferred. Researchers have recently found ways to formulate some glycopeptide antibiotic therapeutic drugs in aqueous solution at refrigerated or room temperature.