Cyclodextrin-Efavirenz Complexes Investigated by Solid State and Solubility Studies

Abstract

This short paper investigates the solubilizing ability of various cyclodextrins with efavirenz as well as the formation of solid inclusion complexes of efavirenz with β-CD and γ-CD. (1) Background: Efavirenz is a non-nucleoside reverse transcriptase inhibitor used as first-line treatment for adult and pediatric human immunodeficiency virus type 1 infection (HIV-1). Belonging to class II of Biopharmaceutical Classification System (BCS), efavirenz is poorly water-soluble. Inclusion into cyclodextrins is a possible strategy for increasing its solubility. (2) Methods: Solubility modulation was investigated by the phase solubility method; inclusion of efavirenz with β- and γ-cyclodextrins was attempted by co-dissolution with co-precipitation; the precipitates were studied by DSC, FT-IR, powder X-ray diffraction and optical microscopy. (3) Results: Solid state analysis of the precipitates shows evidence of separate recrystallization of β-cyclodextrin and efavirenz, whereas in the case of γ-cyclodextrin, a single new phase was observed. (4) Conclusion: Results show that the cavity of β-cyclodextrin is too narrow to accommodate efavirenz and only γ-cyclodextrin, the largest of native cyclodextrins, is able to form a true inclusion complex with this bulky guest.

Inclusion Compound of Efavirenz and γ-Cyclodextrin: Solid State Studies and Effect on Solubility

“…Our results were, therefore, in good agreement with the findings of Sathigari et al [19]. In the batch of efavirenz and γ-CD, a new, low-crystalline phase was formed, indicating the formation of an inclusion complex [20]. The preliminary findings on the formation of γ-CD•EFC prompted further investigation on this host-guest system, which is herein presented.…”

“…Regarding HPβCD, the literature shows contradictory data, one study depicting it as a good solubiliser, with 60 mM increasing EFV solubility to roughly 1 mM [19], whereas our previous report, in which the isotherm data were collected under the same conditions as those of the present study, revealed it to perform worse than γ-CD, since a concentration of 125 mM of HPβCD was required to solubilise ca. 0.5 mM of EFV [20]. Our study also evaluated HPγCD, which had an isotherm similar to that of HPβCD up to 150 mM and performed slightly worse at higher concentrations [20].…”

“…The study, conducted by Sathigari et al, further showed that the freeze-dried adducts with RAMEB and HPβCD increased efavirenz solubility in water (at 180 min) from 5.64 ± 1.149% (pure drug) to 54.25 ± 1.031% and 43.13 ± 0.331%, respectively. In a preliminary approach to the inclusion of efavirenz into native cyclodextrins, we investigated the possibility of using β-CD and γ-CD as hosts for efavirenz [20]. Efavirenz and each cyclodextrin were co-dissolved in a water/alcohol solution and the mixture was co-precipitated by cooling; in the batch of efavirenz with β-CD, the precipitate consisted of crystals of the two separate components [20], which confirmed that β-CD does not have adequate cavity size for efavirenz.…”

“…In a preliminary approach to the inclusion of efavirenz into native cyclodextrins, we investigated the possibility of using β-CD and γ-CD as hosts for efavirenz [20]. Efavirenz and each cyclodextrin were co-dissolved in a water/alcohol solution and the mixture was co-precipitated by cooling; in the batch of efavirenz with β-CD, the precipitate consisted of crystals of the two separate components [20], which confirmed that β-CD does not have adequate cavity size for efavirenz. Our results were, therefore, in good agreement with the findings of Sathigari et al [19].…”

Cyclodextrins in the antiviral therapy

“…Due to its structural properties, this molecule appears to be less appropriate for strong interaction with most CDs. The use of βCD nanosuspension [132], γCD [133], HPβCD [133,134] and -γCD [133], or RAMEB [135] could improve its physicochemical (≈10-80-fold solubility enhancements) and pharmacokinetic properties (≈3-fold dissolution rate). Those compositions required a third component to achieve the desired effects.…”