Enhanced Bromhexine Hydrochloride Solubility and Dissolution by Inclusion Complexation with Methylated β-cyclodextrin

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 (M\βCD). Inclusion complexes in 11 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 11 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.