Preformulation studies for the development of a microemulsion formulation from Ambrosia peruviana All, with anti-inflammatory effect

Abstract Natural products are considered an important source of the therapeutic arsenal currently available. Among these alternatives are the seeds of Ambrosia peruviana (altamisa), whose extract has shown an anti-inflammatory effect. The main objective of this work was to perform a preformulation study of Ambrosia peruviana seeds ethanolic extract, where the main factors that affect the physical, chemical, and pharmacological stability of the extract were evaluated, as well as a compatibility study by differential scanning calorimetry (DSC) analysis against different excipients. A dry extract was obtained by rotary evaporation of the seeds macerated with 96% ethanol. The anti-inflammatory activity was determined by measuring its effect on NO production in RAW 264.7 macrophages, stimulated with LPS. The results showed that the dry extract maintained its stability over time when stored at a temperature of 4 and 25ºC, demonstrating its biological activity, the content of phenolic compounds, and its physicochemical parameters remain practically invariable. However, when exposed to high temperatures (60 ºC) it was affected. The thermal analysis revelated that the behavior of most of the selected excipients and the dry extract was maintained, which indicates that it did not present incompatibilities, therefore they can be candidates for formulating a microemulsion.

Assessing compatibility of excipients selected for a sustained release formulation of bilberry leaf extract

Abstract The study is aimed to assess the compatibility of bilberry leaf powder extract (BLPE) with six excipients selected for sustained-release (SR) tablet formulation. The BLPE was obtained with the addition of L-arginine and Myo-inositol as the carriers. Thermogravimetric (TG-DTG) analysis and Fourier-transform infrared spectroscopy (FTIR), supported by Pearson correlation analysis, were applied to detect possible interactions in the binary mixtures (1:1) of the BLPE with each excipient. The TG-DTG showed some deviations in the thermal behavior of the BLPE / excipient mixtures. However, only the thermal behavior of magnesium stearate in the mixture significantly differed from individual samples, which suggested chemical interaction for this excipient. The FTIR analysis confirmed that the BLPE is compatible with Eudragit L100, Methocel K4M, Methocel K100LV, Avicel PH-101, and Plasdone S-630. Whereas it undergoes solid-state chemical interaction in the binary mixture with magnesium stearate. According to the FTIR-spectra, it is suggested that this interaction results in the formation of stearic acid and alkalization of the medium. These findings evidence for the possibility of using TG-DTG analysis as an independent thermal technique for compatibility studies and also confirm the earlier reported interaction of basic lubricants, e.g., stearic salts, with active ingredients containing amino groups.

Solubility and dissolution enhancement of flurbiprofen by solid dispersion using hydrophilic carriers

ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05) in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%). The mean dissolution time (MDT) was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min.) indicating faster drug release. The DE (% dissolution efficiency) was increased by 2.5 folds (61.63%) compared to conventional tablets (23.71%). From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.

Caracterização no estado sólido e compatibilidade farmacêutica de cloridrato de ziprasidona / Solid-state characterization and pharmaceutical compatibility of ziprasidone hydrochloride

O cloridrato de ziprasidona foi físico-quimicamente caracterizado pelas técnicas de Calorimetria Exploratória Diferencial (DSC), Termogravimetria (TG), Espectroscopia no Infravermelho com Transformada de Fourier (FT-IR), Difração de Raios X de Pó (DRX) e Microscopia Eletrônica de Varredura (MEV). O estudo de compatibilidade foi realizado com 5 excipientes farmacêuticos diferentes (amido pré-gelatinizado, estearato de magnésio, celulose microcristalina, manitol e polivinilpirrolidona ­ PVP) . Amostras de misturas binárias fármaco: excipiente 1:1 m/m foram estocadas por 3 meses em câmara de estabilidade (75% ± 5% de umidade relativa e 40 ºC ± 1 ºC), e então analisadas por Cromatografia Líquida de Alta Eficiência (CLAE) para avaliar o efeito de cada excipiente na estabilidade química e, consequentemente, no teor do fármaco, em cada amostra . Os resultados de DRX e FT-IR identificaram a forma polimórfica F, correspondente ao cloridrato de ziprasidona monohidrato. A análise térmica demonstrou que o fármaco apresentou uma perda de massa de 4%, até 100ºC, correspondente à saída de uma molécula de água. A próxima perda de massa ocorreu a partir da temperatura de fusão (297ºC), e o fármaco foi totalmente degradado até 600ºC. Os resultados de CLAE demonstraram que o estearato de magnésio foi o único, entre os 5 excipientes testados, que provocou uma redução significativa de teor do fármaco na amostra (teor encontrado = 77% ± 3%). Dessa forma, o fármaco foi compatível com amido pré-gelatinizado, celulose microcristalina, manitol e PVP; e incompatível com estearato de magnésio nas condições estudadas.

Ziprasidone hydrochloride was fully characterized by Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Fourier Transform Infrared Spectroscopy (FT-IR), Powder X-ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM). The stability study was carried out with 5 different pharmaceutical excipients (pregelatinized starch, magnesium stearate, microcrystalline cellulose, mannitol, polyvinylpyrrolidone ­ PVP). Binary mixtures of the drug-excipient were prepared in a 1:1(w/w) ratio and stored for 3 months in stability chamber (75% ± 5% of relative humidity and temperature of 40 ºC ± 1 ºC), then these samples were analyzed by High Performance Liquid Chromatography (HPLC) to evaluate the effect of each excipient on chemical stability and, consequently, on amount of drug in each sample. Data obtained by FT-IR and PXRD shown the polymorphic form F, corresponding to monohydrate ziprasidone hydrochloride. The thermal analysis demonstrated a mass loss of 4% until 100ºC, corresponding to a water molecule. The following mass loss occurred from melting temperature (297ºC) to 600ºC, with total sample degradation. The HPLC results shown that, between 5 tested excipients, only magnesium stearate caused significant amount reduction of drug in the sample (amount found = 77% ± 3%). Then, the drug was compatible with pregelatinized starch, microcrystalline cellulose, mannitol and PVP; and incompatible with magnesium stearate, in these work conditions.