Enhanced Bromhexine Hydrochloride Solubility and Dissolution by Inclusion Complexation with Methylated β-cyclodextrin
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Abstract
The aim of this study was to enhance the solubility and dissolution of bromhexine hydrochloride by inclusion complexation with the cyclodextrin derivative, methylated β-cyclodextrin (MβCD). Inclusion complexes in 1:1 molar ratio were prepared by the kneading and coevaporation methods. The solubility of drug in methylated β-cyclodextrin was studied. The complexes were characterized by differential scanning calorimetry (DSC), X-ray diffractometry, Fourier transform infrared (FT-IR) spectroscopy and dissolution studies. The solubility of bromhexine hydrochloride increased linearly with the concentration of methylated β-cyclodextrin. The phase-solubility profile was classified as AL-type, indicating the formation of a 1:1 stoichiometric inclusion complex with an apparent stability constant (Ks) of 110 M⁻¹. The crystallinity of drug from inclusion complexes was reduced. The inclusion complex prepared by the coevaporation method showed interaction between drug and methylated β-cyclodextrin. Both kneaded and coevaporated samples gave similar dissolution profiles; of 50-, and 5-fold increases in drug dissolution were observed within the first 5 mins compared to pure drug and physical mixtures, respectively. These inclusion complexes were effective in enhancing drug dissolution, with bromhexine hydrochloride completely dissolving within 10 mins.
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