Embedding a Sensitive Liquid-Core Waveguide UV Detector into an HPLC-UV System for Simultaneous Quantification of Differently Dosed Active Ingredients during Drug Release

Abstract

Individual dosing of pharmaceutics and personalized medicine have become important with regard to therapeutic safety. Dose adjustments, biorelevant drug release and combination of multiple active substances in one dosage form for the reduction in polymedication are essential aspects that increase the safety and acceptance of the patient’s pharmacotherapy. Therefore, not only innovative drug products but also new analytical methods are needed during the drug development phase and for quality control that can simultaneously determine different active ingredients and cover wide concentration ranges. We investigated a liquid-core waveguide UV absorbance flow cell detector coupled to an existing HPLC-UV system. A Teflon AF 2400 capillary tubing of 20 cm length was connected in series to the HPLC flow line and enabled a lower limit of quantification of 1 ng/mL pramipexole (increase in sensitivity by 20 compared to common 0.9 cm flow cells). This allowed the low-concentration of pramipexole and the higher concentrations of levodopa and benserazide occurring during drug release to be determined in a single chromatographic run within 22.5 min.

3D Printed Mini-Floating-Polypill for Parkinson’s Disease: Combination of Levodopa, Benserazide, and Pramipexole in Various Dosing for Personalized Therapy

“…After extrusion, parts of the filaments were used for dissolution tests to assess which formulation was most likely to reproduce the desired release profile (SA/V: 2.3 mm −1 ). Parallel quantification of LD and BZ is challenging, and the development of a suitable analytical method to quantify the APIs simultaneous in the presence of PDM is described in another publication [ 76 ]. As other publications have already shown, the release profiles of BZ and LD are comparable [ 93 , 94 , 95 , 96 , 97 ].…”

“…For extrusions with EVA, the screw speed was set to 20 rpm and powder feed rate was set to 2 g/min. The screw configurations and the temperatures of the heating zones are summarized in Table 4 and also described in previous publications [ 60 , 61 , 76 ].…”

“…The volume was 1000 mL, the stirring speed was set to 50 rpm and the temperature was set to 37 ± 0.5 °C. The dissolution tests were performed under sink conditions [ 63 , 76 ]. Samples were drawn using an autosampler (Vision ® AutoFill™ + AutoPlus™, Teledyne Hanson Research, Chatsworth, CA, USA).…”

“…The following method is described in more detail in [ 76 ]. High performance liquid chromatography (HPLC) analysis was used to separate all three APIs (PDM, LD, BZ).…”

Introducing Fiber-Assisted Colorimetric Measurements as a Quality Control Tool of Hot Melt Extruded Filaments

“…For the first method, ammonium acetate buffer and methanol (mobile phase B) served as eluents. The gradient was set as follows: mobile phase B was increased from 1 to 5% ( v/v ), within the first minute, held at 5% ( v/v ) for 4 min, increased from 5 to 10% ( v/v ) within 1 min, held at 10% ( v/v ) for 4 min, increased again from 10 to 20% ( v/v ) within 1 min, held for 4 min at 20% ( v/v ), increased again from 20 to 99% ( v/v ) within 5 min, held for 2 min at 99% ( v/v ) and decreased to 1% ( v/v ) within 0.5 min, again until 22.5 min after sample injection [ 23 ]. An equilibration time of 3.5 min per run was maintained before the next sample was injected.…”