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Poly(2-ethyl-2-oxazoline) (PEOX), a biocompatible polymer considered as pseudopolypeptide, was introduced as a potential alternative to the commonly used polymer, poly(vinylpyrrolidone) (PVP) for the preparation of solid dispersion with a poorly soluble drug. Glipizide (GPZ), a Biopharmaceutical Classification System class II model drug, was selected for solubility and dissolution rate study. GPZ-polymer solid dispersions and physical mixtures were characterized and investigated by X-ray diffractometry, differential scanning calorimetry, scanning electron microscopy, and FTIR spectroscopy. The impact of polymers on crystal nucleation kinetics was studied, and PEOX exhibited strong inhibitory effect compared with PVP. Solubility and dissolution behavior of the prepared solid dispersions and their physical blends were in vitro examined and evaluated. A significant enhancement in GPZ solubility was obtained with PEOX compared with the pure drug and solid dispersion with PVP. A big improvement in the intrinsic dissolution rate (45 times) and dissolved amount of GPZ (58 times) was achieved with PEOX in fasted state simulated intestinal fluid, against comparable enhancement observed with PEOX and PVP in phosphate buffer at pH 6.8. Lower molecular weight of PEOX-5K (5000 g/mol) was found to be superior to higher molecular weight PEOX-50K (50,000 g/mol) in the improvement of dissolution behavior. The findings of this study with GPZ as a model drug introduce lower molecular weight PEOX as a promising polymeric carrier toward better oral bioavailability of poorly soluble drugs.

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A novel, simple and specific spectrofluorimetric method was developed and validated for the determination of perindopril erbumine (PDE). The method is based on the fluorescence quenching of Rhodamine B upon adding perindopril erbumine. The quenched fluorescence was monitored at 578 nm after excitation at 500 nm. The optimization of the reaction conditions such as the solvent, reagent concentration, and reaction time were investigated. Under the optimum conditions, the fluorescence quenching was linear over a concentration range of 1.0-6.0 μg/mL. The proposed method was fully validated and successfully applied to the analysis of perindopril erbumine in pure form and tablets. Statistical comparison of the results obtained by the developed and reference methods revealed no significant differences between the methods compared in terms of accuracy and precision. The method was shown to be highly specific in the presence of indapamide, a diuretic that is commonly combined with perindopril erbumine. The mechanism of rhodamine B quenching was also discussed.

A new cocrystal of Norfloxacin, a poorly soluble fluoroquinolone antibiotic, has been synthetized by a solvent-mediated transformation experiment in toluene, using resorcinol as a coformer. The new cocrystal exists in both anhydrous and monohydrate forms with the same (1:1) Norfloxacin/resorcinol stoichiometry. The solubility of Norfloxacin and the hydrated cocrystal were determined by the shake-flask method. While Norfloxacin has a solubility of 0.32 ± 0.02 mg/mL, the cocrystal has a solubility of 2.64 ± 0.39 mg/mL, approximately 10-fold higher. The dissolution rate was tested at four biorelevant pH levels of the gastrointestinal tract: 2.0, 4.0, 5.5, and 7.4. In a first set of comparative tests, the dissolution rate of Norfloxacin and the cocrystal was determined separately at each pH value. Both solid forms showed the highest dissolution rate at pH 2.0, where Norfloxacin is totally protonated. Then, the dissolution rate decreases as pH increases. In a second set of experiments, the dissolution of the cocrystal was evaluated by a unique dissolution test, in which the pH dynamically changed from 2.0 to 7.4, stepping 30 min at each of the four biorelevant pH values. Results were quite different in this case, since dissolution at pH 2 affects the behavior of Norfloxacin at the rest of the pH values.