ABSTRACT
@#This study aimed to identify the related substances of midazolam hydrochloride by liquid chromatography-mass spectrometry (LC-MS). To separate the related substances of midazolam hydrochloride, gradient elution was performed using acetonitrile and 25 mmol/L of ammonium acetate (pH was adjusted to 5.5 with acetic acid) as mobile phase on Thermo BDS Hypersil C18 column (100 mm × 4.6 mm, 2.4 μm). The accurate mass and elemental composition of the parent ions and their product ions of related substances were determined by electrospray-ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF/MS). The structures of the related substances were identified by spectral analysis and process synthesis, and some of them were further confirmed by reference substances. Under the established HPLC condition, midazolam hydrochloride and its related substances were adequately separated, and 22 major related substances were detected and identified by hyphenated techniques in midazolam hydrochloride and its stressed samples, of which 8 were recorded as impurities in the United States Pharmacopeia. The LC-MS techniques can effectively separate and identify the related substances of midazolam hydrochloride and provide reference for the establishment of storage condition, optimization of synthetic processes and quality control.
ABSTRACT
Nasal drug delivery systems prepared from natural materials are gaining importance in the field of pharmaceutical technology. Mucilage isolated from Linum usitatissimum L. (LUM) seeds was reported to be an effective natural mucoadhesive agent. The present study deals with a comparison of various characteristics of nasal gels containing midazolam hydrochloride (HCl) prepared from mucoadhesive agent extracted from Linum usitatissimum L. seeds and synthetic polymers like HPMC and Carbopol 934P in terms of texture profile analysis, mucoadhesive strength, and in vivo drug absorption profiles. It was observed that gels formulated with the natural mucilage showed better results than the synthetic gels in all aspects like hardness, adhesiveness, cohesiveness and mucoadhesive strength. The absolute bioavailability of midazolam hydrochloride from the natural gel was 97.55 percent whereas that of synthetic gels was 57.33 percent and 76.81 percent respectively.
Sistemas de liberação nasal preparados com produtos naturais estão ganhando importância no campo da tecnologia farmacêutica. A mucilagem isolada de sementes de Linum usitatissimum L. (LUM) mostrou-se agente mucoadesivo eficaz. O presente estudo trata da comparação de várias características de géis nasais contendo cloridrato de midazolam preparados com agente mucoadesivo extraído das sementes de Linum usitatissimum L. e com polímeros sintéticos, como HPMC e Carbopol 943P, com relação ao perfil de textura, força mucoadesiva e perfis de absorção do fármaco in vivo. Observou-se que os géis formulados com mucilagem natural apresentam melhores resultados do que os sintéticos em todos os aspectos, como dureza, adesão, coesão e força mucoadesiva. A biodisponibilidade absoluta do cloridrato de midazolam a partir do gel natural foi de 97,55 por cento, enquanto que nos géis sintéticos foi de 57,33 por cento e 76,81 por cento, respectivamente.