Changes in the protonation state of lyophilized proteins can impact structural integrity, chemical stability, and propensity to aggregate upon reconstitution. When a buffer is chosen, the freezing/drying process may result in dramatic changes in the protonation state of the protein due to ionization shift of the buffer. In order to determine whether protonation shifts are occurring, ionizable probes can be added to the formulation. Optical probes (dyes) have shown dramatic ionization changes in lyophilized products, but it is unclear whether the pH indicator is uniform throughout the matrix and whether the change in the pH indicator actually mirrors drug ionization changes. In solid-state NMR (SSNMR) spectroscopy, the chemical shift of the carbonyl carbon in carboxylic acids is very sensitive to the ionization state of the acid. Therefore, SSNMR can be used to measure ionization changes in a lyophilized matrix by employing a small quantity of an isotopically-labeled carboxylic acid species in the formulation. This paper compares the apparent pH of six trehalose-containing lyophilized buffer systems using SSNMR and UV-Vis diffuse reflectance spectroscopy (UVDRS). Both SSNMR and UVDRS results using two different ionization probes (butyric acid and bromocresol purple, respectively) showed little change in apparent acidity compared to the pre-lyophilized solution in a sodium citrate buffer, but a greater change was observed in potassium phosphate, sodium phosphate, and histidine buffers. While the trends between the two methods were similar, there were differences in the numerical values of equivalent pH (pHeq) observed between the two methods. The potential causes contributing to the differences are discussed.
- MeSH
- fosfáty * chemie MeSH
- histidin * chemie MeSH
- koncentrace vodíkových iontů MeSH
- kyselina citronová chemie MeSH
- lyofilizace * metody MeSH
- magnetická rezonanční spektroskopie * metody MeSH
- pufry MeSH
- spektrofotometrie ultrafialová metody MeSH
- trehalosa * chemie MeSH
- Publikační typ
- časopisecké články MeSH
A new targeted intravenous conjugate of nystatin with pentaerythritol poly(ethylene glycol)ether has been prepared and characterised (NY(4)-sPEG, M=25 160). The conjugate contains a beta-d-glucopyranoside molecular switch sensitive to beta-glucosidases (E.C.3.2.1.21), which are specifically present in the enzyme outfit of fungal pathogens. The investigated conjugate is stable under in vitro conditions for 24h (solution of phosphate buffer pH=7.4). Spectrophotometrically controlled releasing of nystatin in model medium containing beta-glucosidase ((Aspergillus niger) 2mg/mL, 66.6 units/g; pH 7.4, 2 x 10(-2)M), reported decomposition half-life of conjugate tau(1/2)=(88+/-2)s. This implies that releasing of nystatin is controlled only enzymatically.
- MeSH
- antifungální látky aplikace a dávkování chemie metabolismus MeSH
- Aspergillus niger enzymologie MeSH
- celulasy izolace a purifikace metabolismus MeSH
- chemie farmaceutická MeSH
- farmaceutická technologie metody MeSH
- gelová chromatografie MeSH
- hydrolýza MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- léky s prodlouženým účinkem MeSH
- magnetická rezonanční spektroskopie MeSH
- nosiče léků MeSH
- nystatin aplikace a dávkování chemie metabolismus MeSH
- poločas MeSH
- polyethylenglykoly chemie MeSH
- příprava léků MeSH
- propylenglykoly chemie MeSH
- pufry MeSH
- rozpustnost MeSH
- spektrofotometrie ultrafialová MeSH
- stabilita léku MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
3-[4-(2-Methylpropyl)phenyl]propanoic acid has been introduced as impurity F to the European Pharmacopoeia in its Supplement 4.2. In contrast to other impurities, which are evaluated by HPLC, the content of impurity F is determined by gas chromatography after previous derivatization. Thus a novel reversed-phase HPLC method was developed to simplify the evaluation of pharmacopoeial impurity F of ibuprofen. Favourable properties of zirconia stationary phases were employed for this purpose. The HPLC separation was achieved on a Zr-CARB column (150 mm x 4.6mm i.d., 5 microm) using the mobile phase acetonitrile-phosphate buffer (pH 3.5, 25 mM) (38:62, v/v), temperature 80 degrees C and the flow rate 1.2 ml min(-1). The fluorescence detection was employed to enhance the sensitivity of the method. Optimal detection parameters were chosen on the basis of fluorescence spectra of the analytes. The excitation and emission wavelengths were 220 nm and 285 nm, respectively. The analysis was completed within 25 min. The subsequent validation of the method confirmed the applicability of method for the analytical assay of impurity F.
- MeSH
- antiflogistika nesteroidní chemie izolace a purifikace MeSH
- časové faktory MeSH
- farmakopea jako téma MeSH
- ibuprofen chemie izolace a purifikace MeSH
- koncentrace vodíkových iontů MeSH
- kontaminace léku MeSH
- léčivé přípravky analýza MeSH
- molekulární struktura MeSH
- molekulová hmotnost MeSH
- propionáty analýza MeSH
- pufry MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- spektrofotometrie ultrafialová MeSH
- stereoizomerie MeSH
- teplota MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zirkonium chemie MeSH
- Publikační typ
- práce podpořená grantem MeSH
A novel fast isocratic reversed-phase HPLC method for simultaneous determination of chlorhexidine and its degradation product p-chloroaniline was developed. Zorbax SB Phenyl column (75 mm x 4.6 mm, 3.5 microm) was used for the separation. Mobile phase composed of acetonitrile and buffer solution of 0.08 M sodium phosphate monobasic containing 5 ml of triethylamine (0.5%) and adjust with 85% phosphoric acid to pH 3.0 in ratio 35:65 (v/v) pumped isocratically at flow rate 0.6 ml min(-1) was used. UV detection was performed at 239 nm, the total analysis time was about 10 min. The method is suitable for practical routine analysis of topical ointment in the quality control laboratory.
- MeSH
- acetonitrily MeSH
- aniliny analýza MeSH
- aplikace lokální MeSH
- chlorhexidin analogy a deriváty analýza MeSH
- financování organizované MeSH
- indikátory a reagencie MeSH
- koncentrace vodíkových iontů MeSH
- masti analýza MeSH
- pufry MeSH
- referenční standardy MeSH
- reprodukovatelnost výsledků MeSH
- řízení kvality MeSH
- spektrofotometrie ultrafialová MeSH
- veterinární léky MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- MeSH
- elektroforéza kapilární metody MeSH
- lidé MeSH
- pufry MeSH
- spektrofotometrie ultrafialová MeSH
- thioglykoláty moč MeSH
- Check Tag
- lidé MeSH
