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

Tayel A Al Hujran,Hesham M Tawfeek,Samer Al-Gharabli,Rula R Haddadin,Manal N Al Soub,Mousa K Magharbeh

doi:10.3390/pharmaceutics13070994

Tayel A Al Hujran, Hesham M Tawfeek + Show 4 more

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https://doi.org/10.3390/pharmaceutics13070994

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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.

Highlights

The supramolecular chemistry showed a broad interest during the last few decades in different aspects of applications such as electrochemical sensors, catalysis, drug delivery systems, biotherapy, and self-healing [1,2,3,4]
Phase solubility diagram of ME at 25 ± 0.5 ◦ C in the presence of increasing concentrations of sulfonatocalix[4]naphthalene was obtained by plotting equilibrium concentrations of the drug against sulfonatocalix[4]naphthalene concentrations as shown in Figure 1, according to the method reported by Higuchi and Connors [43]
The constructed phase solubility curves could be classified as AL type, which suggested the formation of the 1:1 water-soluble ME-sulfonatocalix[4]naphthalene inclusion complex

Summary

Introduction

The supramolecular chemistry showed a broad interest during the last few decades in different aspects of applications such as electrochemical sensors, catalysis, drug delivery systems, biotherapy, and self-healing [1,2,3,4]. New macrocycles were synthesized such as crown ethers [5], calix[n]arenes [6], etc., which have the ability to host different types of molecules for numerous applications [6]. Calix[n]arenes are cyclic oligomers that have different sizes depending on the number of the repeated phenolic unit, ranging from 4 to 8 units [7,8,9,10]. This type of macrocyclic has a well-defined deep hydrophobic cavity surrounded by a hydrophobic upper rim and hydrophilic lower rim.

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