Studying the Complex Formation of Sulfonatocalix[4]naphthalene and Meloxicam towards Enhancing Its Solubility and Dissolution Performance

Abstract

The interaction between meloxicam and sulfonatocalix[4]naphthalene was investigated to improve the meloxicam solubility and its dissolution performance. Solubility behavior was investigated in distilled water (DW) and at different pH conditions. Besides, solid systems were prepared in a 1:1 molar ratio using coevaporate, kneading, and simple physical mixture techniques. Further, they were characterized by PXRD, FT-IR, DCS, and TGA. In vitro dissolution rate for coevaporate, kneaded, and physical mixture powders were also investigated. Solubility study revealed that meloxicam solubility significantly increased about 23.99 folds at phosphate buffer of pH 7.4 in the presence of sulfonatocalix[4]naphthalene. The solubility phase diagram was classified as AL type, indicating the formation of 1:1 stoichiometric inclusion complex. PXRD, FT-IR, DCS, and TGA pointed out the formation of an inclusion complex between meloxicam and sulfonatocalix[4]naphthalene solid powders prepared using coevaporate technique. In addition, in vitro meloxicam dissolution studies revealed an improvement of the drug dissolution rate. Furthermore, a significantly higher drug release (p ≤ 0.05) and a complete dissolution was achieved during the first 10 min compared with the other solid powders and commercial meloxicam product. The coevaporate product has the highest increasing dissolution fold and RDR10 in the investigated media, with average values ranging from 5.4–65.28 folds and 7.3–90.7, respectively. In conclusion, sulfonatocalix[4]naphthalene is a promising host carrier for enhancing the solubility and dissolution performance of meloxicam with an anticipated enhanced bioavailability and fast action for acute and chronic pain disorders.

Insight into the Inclusion Complexation of Fluconazole with Sulfonatocalix[4]naphthalene in Aqueous Solution, Solid-State, and Its Antimycotic Activity

“…The DSC thermogram of sulfonatocalix[4]naphthalene showed two major endothermic events at 108.0 °C and 750.0 °C, attributed to its dehydration and fusion or decomposition [ 29 ]; respectively. The results showing the decreased intensity of the endothermic melting point peak of FZ and shifted to the lower temperature around 137.9 °C and 137.0 °C, respectively, were revealed through thermograms of the physical and kneaded powder products of the drug host.…”

“…The results showing the decreased intensity of the endothermic melting point peak of FZ and shifted to the lower temperature around 137.9 °C and 137.0 °C, respectively, were revealed through thermograms of the physical and kneaded powder products of the drug host. This result could be due to the lowering of FZ crystallinity due to mixing with amorphous sulfonatocalix[4]naphthalene, and the formation of a partial inclusion complex or the presence of FZ is an ultrafine crystallite [ 29 , 42 ].…”

“…For further investigation of the possibility and kind of physicochemical interactions between FZ and the utilized host molecule, FT-IR spectra were obtained for pure FZ, sulfonatocalix[4]naphthalene, and their solid powders generated via physical mixing, kneading, and co-evaporate procedures. Spectrum of sulfonatocalix[4]naphthalene [ 29 , 76 ] exhibited characteristic broadband in the region of 2900–3600 cm −1 , corresponding to the starching vibration of naphthalene hydroxyl groups ( Figure 6 a). The stretching vibration of the double bond in naphthalene aromatic rings was ascribed to the other peaks in 1632 to 1572 cm −1 .…”

“…The results showing the decreased intensity of the endothermic melting point peak of FZ and shifted to the lower temperature around 137.9 °C and 137.0 °C, respectively, were revealed through thermograms of the physical and kneaded powder products of the drug host. This result could be due to the lowering of FZ The DSC thermogram of sulfonatocalix [4]naphthalene showed two major endothermic events at 108.0 • C and 750.0 • C, attributed to its dehydration and fusion or decomposition [29]; respectively. The results showing the decreased intensity of the endothermic melting point peak of FZ and shifted to the lower temperature around 137.9 • C and 137.0 • C, respectively, were revealed through thermograms of the physical and kneaded powder products of the drug host.…”

“…This limitation is overcome by developing various techniques to improve the physicochemical properties of those types of drugs such as solid dispersions [44], The sulfonatocalix [4]naphthalene macrocycle has unique properties, such as higher water solubility and large cavity size compared with CD's and p-sulfonatocalix[n]arene macrocycles (Figure 1, compound 2) [25][26][27][28]. We have earlier reported the complexation study of sulfonatocalix [4]naphthalene with meloxicam, which showed an improvement in water solubility and enhancement of the dissolution performance of the drug [29].…”