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Cyclodextrins (CDs) are cyclic oligosaccharides of natural origin that were discovered more than 100 years ago. The peculiar cone-like conformation of the sugar ring, expressing a lipophilic cavity and a hydrophilic external surface, allows these substances to spontaneously complex poorly soluble compounds in an aqueous environment. For more than 50 years, these substances have found applicability in the pharmaceutical and food industries as solubilizing agents for poorly soluble chemical entities. Nowadays, several research groups all over the world are investigating their potential as active pharmaceutical ingredients (APIs) for the treatment of several illnesses (e.g., hypercholesterolemia, cancer, Niemann-Pick Type C disease). The aim of this review is to briefly retrace cyclodextrins’ legacy as complexing agents and describe the current and future prospects of this class of chemical entities in pharmaceutics as new APIs.

Many biologically active compounds feature low solubility in aqueous media and, thus, poor bioavailability. The formation of the host-guest complex by using calixarene-based macrocycles (i.e., resorcinol-derived cyclic oligomers) with a good solubility profile can improve solubilization of hydrophobic drugs. Herein, we explore the ability of resorc[4]arenes to self-assemble in polar solutions, to form supramolecular aggregates, and to promote water-solubility of an isoflavone endowed with anti-cancer activity, namely Glabrescione B (GlaB). Accordingly, we synthesized several architectures featuring a different pattern of substitution on the upper rim including functional groups able to undergo acid dissociation (i.e., carboxyl and hydroxyl groups). The aggregation phenomenon of the amphiphilic resorc[4]arenes has been investigated in a THF/water solution by UV–visible spectroscopy, at different pH values. Based on their ionization properties, we demonstrated that the supramolecular assembly of resorc[4]arene-based systems can be modulated at given pH values, and thus promoting the solubility of GlaB.

It is known that males and females respond differently to medicines and that differences in drug behaviour are due to inter-individual variability and sex specificity. In this work, we have examined the influence of pharmaceutical excipients on drug bioavailability in males and females. Using a rat model, we report that a portfolio of polyoxyethylated solubilising excipients (polyethylene glycol 2000, Cremophor RH 40, Poloxamer 188 and Tween 80) increase ranitidine bioavailability in males but not in females. The in vivo sex and excipient effects were reflected in vitro in intestinal permeability experiments using an Ussing chamber system. The mechanism of such an effect on drug bioavailability is suggested to be due to the interaction between the excipients and the efflux membrane transporter P-glycoprotein (P-gp), whose expression in terms of gene and protein levels were inhibited by the solubilising agents in male but not in female rats. In contrast, the non-polyoxyethylated excipient, Span 20, significantly increased ranitidine bioavailability in both males and females in a non-sex-dependent manner. These findings have significant implications for the use of polyoxyethylated solubilising excipients in drug formulation in light of their sex-specific modulation on the bioavailability of drugs that are P-gp substrates. As such, pharmaceutical research is required to retract from a ‘one size fits all’ approach and to, instead, evaluate the potential impact of the interplay between excipients and sex on drug effect to ensure effective pharmacotherapy.

In this study, we designed and prepared two new β-cyclodextrins ( 1 and 2 ) bearing ethylene glycol chains to develop highly water-soluble cyclodextrins. They had excellent water solubility and could successfully dissolve 17-β-estradiol in water, which was considered a poorly soluble drug model. Additionally, the nuclear magnetic resonance structural analysis of a mixed sample of 17-β-estradiol and 1 in D 2 O–H 2 O suggested two different types of inclusion complexes with different 17-β-estradiol molecule orientations inside the cavity of 1 . Graphical abstract

Context: (-)-α-Bisabolol (BISA) is a sesquiterpene alcohol widely used as scent in cosmetic preparations, perfumes, shampoos, toilet soaps and other toiletries with potential for use in the pharmaceutical area.Objective: To evaluate the corneal antinociceptive efficacy of BISA and to analyze the best solubilizing agent.Materials and methods: Acute corneal nociception was induced by the local application of hypertonic saline (5 M NaCl; 20 μL) to the corneal surface of Swiss mice (n = 8/group) 60 min after topical treatment with solutions or ointment containing BISA (50–200 mg/mL). The number of eye wipes performed with the ipsilateral forepaw was counted for a period of 30 s. Control groups (vehicles) were included.Results: BISA (50, 100 or 200 mg/mL) solubilized with Tween 80 did not reduce the number of eye wipes. Animals treated with the ointment (BISA 50, 100 or 200 mg/mL; p < 0.001), as well the solution containing propylene glycol (BISA 100 mg/mL; p < 0.05), showed significant reduction in the number of nociceptive behaviours. Solutions containing propylene glycol and isopropyl myristate had no effects.Discussion and conclusion: BISA possess corneal antinociceptive activity. Although the ointment presented antinociceptive effect, it is concluded that BISA when associated with propylene glycol has better potential for corneal nociceptive pain since it is more comfortable to use, leading to greater acceptance by patients.

The delivery of therapeutics preferentially to target tissue remains a considerable barrier to achieving effective clinical outcomes; this ultimately requires a molecule to display both optimal hydrophilic and lipophilic properties. cyclodextrins (CDs) are successfully applied as drug solubilizing agents and they are now routinely employed for this purpose in a range of pharmaceutical formulations. The literature boasts a range of methods for the formation of drug‐CD complexes. The solvents and processing parameters used may vary, but the commonly used techniques can be broadly divided into spray drying, freeze drying, slurry method, kneading, solid phase complexation, co‐precipitation, and neutralization. A variety of techniques have been employed to confirm the formation and utility of CD complexes, namely thermo‐analytical methods, differential scanning calorimetry (DSC) or differential thermal analysis (DTA), scanning electron microscopy (SEM), and transmission electron microscopy (TEM).

This chapter emphasizes on improving the pharmacological activity, i.e. potency, of peptide drugs. It concentrates the discussion on enhancing the pharmacokinetic properties of peptide drugs with an emphasis on membrane permeability. “Lipinski’s Rule of Five” described the physicochemical features for a drug’s pharmacokinetics in the human body, including its absorption, distribution, metabolism and excretion (ADME). The chapter discusses the solubilizing agents that are applicable to all routes of administration, namely parenteral, topical and enteral. Most peptide and protein drugs are restricted to the parenteral route because they are susceptible to enzymatic degradation during absorption or cannot be efficiently absorbed into the systemic circulation, due to their large molecular sizes 15 and charge issue. Most type 1 diabetes mellitus patients have to subcutaneously inject insulin multiple times each day while changing their sites of administration, i.e. site rotation, to keep the skin healthy.