Development of Advanced Chemometric-Assisted Spectrophotometric Methods for the Determination of Cromolyn Sodium and Its Alkaline Degradation Products

Advanced and sensitive spectrophotometric and chemometric analytical methods were successfully established for the stability-indicating assay of cromolyn sodium (CS) and its alkaline degradation products (Deg1 and Deg2). Spectrophotometric mean centering ratio spectra method (MCR) and chemometric methods, including principal component regression (PCR) and partial least square (PLS-2) methods, were applied. Peak amplitudes after MCR at 367.8 nm, 373.8 nm and 310.6 nm were used within linear concentration ranges of 2–40 µg mL−1, 5–40 µg mL−1 and 10–100 µg mL−1 for CS, Deg1 and Deg2, respectively. For PCR and PLS-2 models, a calibration set of eighteen mixtures and a validation set of seven mixtures were built for the simultaneous determination of CS, Deg1 and Deg2 in the ranges of 5–13 µg mL−1, 8–16 µg mL−1, and 10–30 µg mL−1, respectively. The authors emphasize the importance of a stability-indicating strategy for the investigation of pharmaceutical products.

Crystallization and Alkaline Degradation Behaviors of Poly(l-Lactide)/4-Armed Poly(ε-Caprolactone)-Block-Poly(d-Lactide) Blends with Different Poly(d-Lactide) Block Lengths

Four-armed poly(ε-caprolactone)-block-poly(d-lactide) (4-C-D) copolymers with different poly(d-lactide) (PDLA) block lengths (Mn,PDLAs) were synthesized by sequential ring-opening polymerization (ROP). The formation of stereocomplex (SC) crystallites in the 80/20 poly(l-lactide) (PLLA)/4-C-D blends were investigated with the change of Mn,PDLA from 0.5 to 1.5 kg/mol. It was found that the crystallization and alkaline degradation of the blends were profoundly affected by the formed SC crystallites. The PLLA/4-C-D0.5 blend had the lowest crystallization rate of the three blends, and it was difficult to see spherulites in this blend by polarized optical microscopy (POM) observation after isothermal crystallization at 140 °C for 4 h. Meanwhile, when Mn,PDLA was 1 kg/mol or 1.5 kg/mol, SC crystallites could be formed in the PLLA/4-C-D blend and acted as nucleators for the crystallization of PLLA homo-crystals. However, the overall crystallization rates of the two blends were still lower than that of the neat PLLA. In the PLLA/4-C-D1.5 blend, the Raman results showed that small isolated SC spherulites were trapped inside the big PLLA homo-spherulites during isothermal crystallization. The degradation rate of the PLLA/4-C-D blend decreased when Mn,PDLA increased from 0.5 to 1.5 kg/mol, and the degradation morphologies had a close relationship with the crystallization state of the blends. This work revealed the gradual formation of SC crystallites with the increase in Mn,PDLA in the PLLA/4-C-D blends and its significant effect on the crystallization and degradation behaviors of the blend films.

Determination of Rufinamide in the Presence of 1-[(2,6-Difluorophenyl)Methyl]-1H-1,2,3-Triazole-4 Carboxylic Acid Using RP-HPLC and Derivative Ratio Methods as Stability Indicating Assays to Be Applied on Dosage Form

Background Rufinamide is a triazole derivative that is structurally dissimilar to other marketed antiepileptic drugs, has been assumed a marketing authorization, by the European Union and FDA, for use as a complementary therapy for seizures associated with Lennox-Gastaut syndrome. Objective This work is concerned with development of two methods for determination of rufinamide (RUF) in presence of 1-[(2,6-difluorophenyl)methyl]-1H-1,2,3-triazole-4 carboxylic acid as its alkaline degradation product in dosage form. Methods The first method was capable of determing RUF in the presence of its alkaline degradation product and in dosage form. Kromasil C8 column and mobile phase consisting of acetonitrile–water (50:50, v/v) were used and UV detection at 210 nm. In the second method, first derivative ratio spectrophotometry, RUF was determined by measuring peak amplitude at 269.5 nm over 5–30 μg/mL. Results The linearity range of RUF was 10–90 μg/mL for HPLC method covering its therapeutic range with r2 = 0.9999. Forced degradation under alkaline conditions was carried out, the degradation product was isolated and its structure was confirmed. Both methods were validated in accordance to ICH guidelines. Statistical analysis revealed no significant difference between obtained results and reported ones. Conclusion The present study is useful for therapeutic drug monitoring and routine analysis of RUF in quality control laboratories. Highlights Kinetics of the alkaline degradation of RUF was studied by following the concentration of the remaining drug until complete degradation was achieved.

Development and Validation of a Simple HPLC-UV Method to Assay DEET Repellents and its Application to Different Commercial Forms

Background: N’,N’-diethyl-m-toluamide (DEET) is the most widely used repellent substance worldwide. It is formulated as aerosol, solution, lotion, gel and patches. However, the official compendia report monographs to analyze only DEET drug substance and solution. Objective: In this study an isocratic HPLC method was validated to assay DEET in lotion, gel and solution, under the same analytical conditions. Method: The method was validated according to ICH requirements and DEET detection was achieved at around 11 min, using C-18 column, a mobile phase composed by methanol, acetonitrile and water pH 4.5 (45:10:45), flow rate at 1 mL min-1 and detection at 270 nm. Results: A linear relationship was observed in the range of 2.5 to 100 µg mL-1, the method was precise (relative standard deviation < 2%) and accuracy was demonstrated by DEET recovery values ranging from 99.5 to 100.2%. The specificity was studied by a forced degradation test, where degradation products were observed after alkaline degradation and ultraviolet radiation. Appropriate resolution between DEET, degradation products and excipient peaks indicated the method specificity. Robustness was evaluated by a full factorial design, and no effect on DEET assay was observed under simultaneous variation in analytical parameters. The method was applied to assay nine marketed formulations, demonstrating its good applicability. Conclusion: The validated HPLC method was successfully applied to the quantitative analysis of DEET in lotion, gel and solution, contributing to improve the quality control and the efficacy of these formulations.