Compatibility and stability of valsartan in a solid pharmaceutical formulation

Abstract

Valsartan (VAL) is a highly selective blocker of the angiotensin II receptor that has been widely used in the treatment of hypertension. Active pharmaceutical ingredient compatibility with excipients (crospovidone, hypromellose, magnesium stearate, microcrystalline cellulose and titanium dioxide) is usually evaluated in solid pharmaceutical development. Compatibility and stability can be evaluated by liquid chromatography. Studies were performed using binary mixtures of 1:1 (w/w) VAL/excipient; samples were stored under accelerated stability test conditions (40 °C at 75% relative humidity). The results indicate that VAL is incompatible with crospovidone and hypromellose, which reduced the VAL content and gave rise to new peaks in the chromatogram due to degradation products. Valsartana (VAL) é um bloqueador altamente seletivo do receptor da angiotensina II, que tem sido amplamente utilizado para o tratamento da hipertensão. Testes de compatibilidade com excipientes usualmente empregados em formulações sólidas são utilizados no desenvolvimento de formulações sólidas. Neste trabalho, realizaram-se testes utilizando misturas binárias na proporção 1:1 (m/m) de VAL/excipiente e as amostras foram armazenadas em condições de estabilidade acelerada (40 °C em 75% de umidade relativa). Os resultados obtidos indicam a incompatibilidade de VAL com crospovidona e hipromelose, através da redução do teor de VAL e a presença de novos picos no cromatograma provenientes de produtos de degradação.Unitermos: Valsartana/compatibilidade. Valtasan/estabilidade. Hipertensão/tratamento. Calorimetria Exploratória Diferencial/análise de fármacos. Cromatografia líquida de alto desempenho/análise quantitativa.

Physical aging of polylactide-valsartan system investigated by differential scanning calorimetry

“…Increase in the glass transition temperature may potentially be a sign of increased stability [17][18][19][20][21][22]. In this case, valsartan may be incorporated as molecular dispersion in a glassy polylactide matrix, stabilized by physical separation of the molecules inside the polymer chains [46].…”

“…Standalone amorphous APIs are rather not used in formulation development. In most cases, amorphous APIs are formulated with excipients in order to, amongst others, provide adequate absorption and to improve their stability [17][18][19][20].…”

Characterization And Compatibility Studies Of Valsartan With Pharmaceutical Excipients

“…Studying the drug-excipient compatibility during the formulation of products is an important process to know any physical and chemical interaction between the compounds. Thermal techniques have been increasingly used for evaluating possible incompatibility quickly through comparison of thermal curves of pure substances with curve obtained from a 1:1 mixture [6]. The characterization of solid-state properties at an early stage by using appropriate analytical methodologies is an essential pre-requisite in the development of solid dosage forms both from scientific and regulatory points of view.…”

LC-MS characterization of valsartan degradation products and comparison with LC-PDA

“…Valsartan (VAL) is a potent and highly selective oral drug largely used for the treatment of hypertension due to its effect as an active antagonist at the angiotensin II AT1-receptor (Krishanaiah et al, 2010) and because its solid-state characterization and compatibility have been established (Julio et al, 2013). In the present study, we report on false Valsartan stability results observed in a degradation study under acid stress condition using HPLC-PDA and the actual instability obtained by HPLC-MS monitoring.…”