Phase Solubility Studies of Poorly Soluble Drug Molecules by Using O-Phosphorylated Calixarenes as Drug-Solubilizing Agents

Abstract

This study is the first report on the solubilizing effect of O-phosphorylated calix [n]arenes that form complexes with neutral molecules such as nifedipine, niclosamide, and furosemide by hostÀguest complexation. These complexation studies were carried out by using the phase solubility technique. From the obtained results, it was observed that the solubility of guest molecules such as nifedipine, niclosamide, and furosemide was significantly increased in the presence of host molecules tetrakis- 4), and octakis-O-(diethoxyphosphoryl)-p-tertbutylcalix[8]arene (5). The increase in solubility of drugs by the calixarene host 1 to 5 was most probably due to inclusion complexation between drug molecules and cavities of the calixarene skeleton similar to drugÀcyclodextrin complexes.

Soft Supramolecular Nanoparticles by Noncovalent and Host–Guest Interactions

“…Their structure is composed of a hydrophobic upper and a hydrophilic lower rim, which surround the hydrophobic hollow cavity ( Figure ). Stabilized by hydrophobic effects, ion–dipole interactions and/or hydrogen bonding, ions or small molecules, such as sugars, amino acids, peptides, hormones, drugs, and proteins, can form inclusion complexes with these supramolecular host molecules. A relatively new class of supramolecular structures are pillar[n]arenes which are structurally comparable to calix[n]arenes.…”

Encapsulation of Drug Molecules into Calix[n]arene Nanobaskets. Role of Aminocalix[n]arenes in Biopharmaceutical Field

“…Thus, enhanced guest complexation can be achieved by selection of appropriate conditions and consideration of host with appropriate cavity geometry. Recently, another research group studied three aforementioned drugs with regard to their ability to form complexes with several phosphonato CAs, substituted at lower and at upper rim . Similarly, the size of the CA's cavity was also assumed as an important factor for complex formation.…”

“…Calixarenes 116-119. at upper rim. 97,98 Similarly, the size of the CA's cavity was also assumed as an important factor for complex formation.…”

Simple Calix[n]arenes and Calix[4]resorcinarenes as Drug Solubilizing Agents

“…The aqueous solubility of both furosemide and nifedipine was increased greatly by complexation with the partially phosphorylated calix [4]arene; in the case of furosemide the phenyl residue again occupied the central cavity. Niclosamide was solubilized by complex formation with paraphosphonatocalix [4]arene and para-phosphonatocalix [6]arene with experimental data again indicating that the substituted aryl residue becomes embedded within the calixarene cavity; this is particularly interesting because the polar nitro group is also taken up by the cavity [64,65]. …”