Potential application of surfactant systems in formulation of dosage forms with slightly soluble substances

Abstract

In order to achieve fast release of ibuprofen, a slightly soluble model substance (0.52×10?4 mol/l), surfactant systems for oral use with different PEG-40 hydrogenated castor oil (C)/diethylene glycol monoethyl ether (T) ratios were investigated. Comparison between dissolution profiles for ibuprofen from formulated systems and from two commercial products, film tablets and soft capsules, is presented in this paper. Photon correlation spectroscopy has shown that after high dilution with water, the surfactant systems were able to form micellar solutions. The size of micelles varied from 14.8±0.075 nm to 16.2±0.021 nm with increasing C/T ratio from 1:2 to 2:1. Although increasing content of PEG-40 hydrogenated castor oil resulted in formation of larger micelles, the lower values of polydispersity index indicated that a more homogeneous distribution of micelle sizes was gained. Conductometric analysis had demonstrated that the system composing of C/T ratio 2:1 showed the most pronounced interaction between droplets, which can be seen as a high rise of electrical conductivity with increasing water content (wwater/wtotal) in the sample. No significant difference in percolation threshold between formulations with different C/T ratios was observed. Different surfactant systems were adsorbed on magnesium aluminometasilicate, as adsorbent with high specific active surface (≈300 m2/g), in order to investigate the potential influence of adsorbent on ibuprofen dissolution rate. Formulated systems, with or without adsorbent, were filled in hard gelatin capsules. The dissolution profiles of ibuprofen from different formulations were obtained in 30 min by dissolution apparatus with rotating baskets and compared with dissolution profiles of ibuprofen from commercial products. For formulations without adsorbent faster release of ibuprofen in the first minutes of the dissolution test, showed formulations with C/T ratio 2:1 and 1:1. Magnesium aluminometasilicate, as adsorbent with high specific surface area, significantly improved release rate of ibuprofen from formulation with C/T ratio 2:1. However, for the formulation with C/T ratio 1:1, significantly lower release of ibuprofen was observed. Formulations with other C/T ratios in terms of fast ibuprofen release did not give satisfying results. The obtained results show that in comparison to dissolution profile of ibuprofen from commercial products proper C/T ratio as well as magnesium aluminometasilicate, as adsorbent with high specific surface area, can significantly increase release of ibuprofen.

U radu je prikazana izrada različitih PEG-40 hidrogenizovano ricinusovo ulje (C)/dietil-englikolmonoetiletar (T) surfaktantnih sistema za peroralnu primenu, radi postizanja bržeg rastvaranja ibuprofena u odnosu na komercijalne preparate tipa film tableta i mekih želatinskih kapsula. Surfaktantni sistemi sa C/T odnosom 1:2, 2:1 i 1:1 okarakterisani su ispitivanjem promene električne provodljivosti sistema sa promenom sadržaja vode (% (mvode/ /mukupno)), kao i merenjem veličine prečnika kapi pri sadržaju vode od 95% (mvode/mukupno). Formulacije C/T odnosa 2:1 i 1:1 pokazale su brže rastvaranje ibuprofena u odnosu na komercijalni preparat. Izrađene formulacije C/T sistema sa ibuprofenom su zatim adsorbovane na magnezijum-aluminijum-metasilikatu, koji kao adsorbens velike specifične aktivne površine, znatno ubrzava rastvaranje ibuprofena pri C/T odnosu 2:1, dok pri drugim C/T odnosima, pozitivan uticaj adsorbensa na brzinu rastvaranja ibuprofena izostaje. Pravilnim odabirom odnosa lekovita supstanca/surfaktant/kosurfaktant/adsorbens, moguće je postići brzo rastvaranje teško rastvorljive lekovite supstance iz čvrstih farmaceutskih oblika.