Stability of Acetazolamide, Baclofen, Dipyridamole, Mebeverine Hydrochloride, Propylthiouracil, Quinidine Sulfate, and Topiramate Oral Suspensions in SyrSpend SF PH4.

The objective of this study was to evaluate the stability of 7 commonly used active pharmaceutical ingredients compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend SF PH4): acetazolamide 25.0 mg/mL, baclofen 10.0 mg/mL, dipyridamole 10.0 mg/mL, mebeverine hydrochloride 10.0 mg/mL, propylthiouracil 5.0 mg/mL, quinidine sulfate 10.0 mg/mL, and topiramate 5.0 mg/mL. All suspensions were stored both at controlled refrigerated (2°C to 8°C) and room temperature (20°C to 25°C). Stability was assessed by measuring the percentage recovery at varying time points throughout a 90-day period. Active pharmaceutical ingredient quantification was performed by ultraviolet (UV) high-performance liquid chromatography, via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredient + vehicle) was at least 90 days for all suspensions with regards to both temperatures. This suggests that SyrSpend SF PH4 is suitable for compounding active pharmaceutical ingredients from different pharmacological classes.

Conformational analysis of the antimalarial agent quinidine.

Quinidine is an active antimalarial compound extracted from the bark of Cinchona trees. The activity differences among structurally related molecules appears to depend on the absolute stereochemistry of some functional groups, a result that stimulated a detailed conformational analysis of these molecules of biological interest. In the present study, the potential energy surface (PES) for the antimalarial agent quinidine (C20H24O2N2) has been comprehensively investigated using the molecular mechanics (MM) and quantum mechanical semiempirical AM1 and PM3 methods. Six distinct minimum energy conformations were located on the multidimensional PES and also characterized as true minima through harmonic frequency analysis. The relative stabilities and thermodynamic properties are reported. The coexistence of different conformers is discussed for the first time in the literature based on the transition state (TS) structures located on the PES for the quinidine molecule. The theoretical results reported in the present study are in agreement with the experimental proposal, based on NMR data, that there are two conformations existing in solution for the quinidine molecule.

Molecular interactions of quinidine with phospholipid bilayers.

Quinidine (QUIN) is one of the most important and efficient antiarrhythmic drugs (AAD). It belongs to class I, which are the drugs that exert their action at the level of the sodium channels in the membrane of the myocard. Several hypotheses support the idea that the molecular mechanism of action of the AAD is via nonspecific interactions with phospholipids sited in the neighborhood of the channels. In order to probe the validity of these hypotheses, QUIN was made to interact with the phospholipids dimyristoylphosphadidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). These interactions were performed in a hydrophobic and a hydrophilic medium under a wide range of molar ratios. The resulting products were analyzed by X-ray diffraction. QUIN solutions were also made to interact with DMPC liposomes, which were studied by fluorescent spectroscopy. Finally, human erythrocytes which were incubated with QUIN solutions were observed by scanning electron microscopy. The results of these experiments proved that QUIN indeed interacted with phospholipid bilayers.

Descontaminación parcial de granulados de polimetacrilatos de quinidina mediante radiaciones gamma y/o envejecimiento / Partial decontamination of quinidine methylmethacrylate granules through gamma radiation and/or aging

Se realizó un estudio de dosificación de radiaciones gamma en la descontaminación parcial de granulados de polimetacrilatos de quinidina y su influencia sobre la estabilidad química de dichos granulados, así como el efecto del envejecimiento de las muestras sobre los resultados microbiológicos obtenidos. Se concluyó que el tratamiento con radiaciones gamma y/o el almacenamiento a largo plazo de los granulados son métodos eficaces para lograr la descontaminación parcial de éstos sin riesgo de afectar su estabilidad química