Table 4.
Effects of some pharmaceutical excipients on the cyclodextrin solubilization.
| Excipients | Examples | Effect on Complexation Enhancement | Some Brief Observations | References |
|---|---|---|---|---|
| Acids, bases, inorganic/organic salts | hydrochloride, citrate, aspartate, mesylate, maleate, tartrate, phosphate, acetate | Increase intrinsic solubility of drugs (S0) and/or the apparent stability constant (K1:1) resulting in increased CE | Salt formation of ziprasidone mesylate enhance the CE of drug up to 100 and 240 times in aqueous HPβCD and SBEβCD solutions when compared with the free base of drug | [71] |
| Ternary complex of terfenadine/βCD/inorganic acid (phosphate, citrate) induce the synergistic effect of CD solubilization | [72] | |||
| The addition of sodium acetate into the complexing medium containing βCD could increase hydrocortisone solubility up to 220% | [73] | |||
| Enhance S0 but in most cases decrease K1:1 | K1:1 of fluasterone/HPβCD complex decreases with increasing ethanol concentration but the drug solubility increased at high ethanol concentration (>40% v/v) | [74] | ||
| Cosolvents | ethanol, propylene glycol (PG) | Ternary complex of diazepam/PG/βCD increased the diazepam solubility than that of the mixture of PG and water | [75] | |
| Hamper complexation by the competitive effect | At higher concentrations of PG, the methyltestosterone solubility in presence of HPβCD decreased possibly due to the complex dissociation | [76] | ||
| Water-soluble polymers | HPMC, Na CMC, PVA, PVP | Formation of ternary complex (drug/CD/polymer) that can increase K1:1 | Polymers and CDs can form water-soluble complexes with poorly water-soluble drugs, for example, acetazolamide, carbamazepine hydrocortisone, naproxen, pregnenolone, tropicamide, etc. have been reviewedSynergistic solubilization effect is possible through micellar-like solubilization or stabilization of self-assembled CD and/or CD complex aggregates | [20,77,78,79] |
| Metal ions | Mg2+ | Enhance CE by increasing S0 via formation of drug/CD/metal ion complexes | Synergistic solubilization of quinolone was obtained when the addition of Mg2+ to the drug/HPβCD complexes | [80] |
Hydroxypropyl methylcellulose (HPMC); sodium carboxymethylcellulose (Na CMC); polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP).