Physicochemical Characterization of Efavirenz–Cyclodextrin Inclusion Complexes

Abstract

Abstract. Efavirenz (EFV) is an oral antihuman immunodeficiency virus type 1 drug with extremely poor aqueous solubility. Thus, its gastrointestinal absorption is limited by the dissolution rate of the drug. The objective of this study was to characterize the inclusion complexes of EFV with β-cyclodextrin (β-CD), hydroxypropyl β-CD (HPβCD), and randomly methylated β-CD (RMβCD) to improve the solubility and dissolution of EFV. The inclusion complexation of EFV with cyclodextrins in the liquid state was characterized by phase solubility studies. The solid-state characterization of various EFV and CD systems was performed by X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy analyses. Dissolution studies were carried out in distilled water using US Pharmacopeia dissolution rate testing equipment. Phase solubility studies provided an A L -type solubility diagram for β-CD and A P -type solubility diagram for HPβCD and RMβCD. The phase solubility data enabled calculating stability constants (K s ) for EFV-βCD, EFV-HPβCD, and EFV-RMβCD systems which were 288, 469, and 1,073 M −1 , respectively. The physical and kneaded mixtures of EFV with CDs generally provided higher dissolution of EFV as expected. The dissolution of EFV was substantially higher with HPβCD and RMβCD inclusion complexes prepared by the freeze drying method. Thus, complexation with HPβCD and RMβCD could possibly improve the dissolution rate-limited absorption of EFV.

SN-38-Cyclodextrin Complexation and Its Influence on the Solubility, Stability, and In Vitro Anticancer Activity Against Ovarian Cancer

“…Some of the intense peaks were at diffraction angles (2θ) of ∼10°, 13°, 24°, and 26°w ith approximate intensities of 968, 612, 887, and 895, respectively. As reported earlier, SBEβCD (33) and RMβCD (15) showed amorphous diffraction patterns. Diffractograms of SN-38-SBEβCD and SN-38-RMβCD complexes were very similar to their corresponding cyclodextrin diffractograms with no sharp peaks of SN-38 suggesting the formation of stable inclusion complexes, whereas their physical mixtures showed some characteristic peaks of SN-38 suggesting the presence of free drug.…”

“…(13). Cyclodextrins have been extensively used to enhance the solubility, mask bitterness, improve stability, improve bioavailability, and decrease tissue irritation upon administration of a variety of poorly soluble drugs (13)(14)(15). Cyclodextrins have been shown to increase the cytotoxicity of several antineoplastic drugs like camptothecin (16,17), curcumin (18), doxorubicin, docetaxel (19), paclitaxel (20), etc.…”

Thermally Triggered Mucoadhesive In Situ Gel of Loratadine: β-Cyclodextrin Complex for Nasal Delivery

“…The thermogram of β-CD (Fig. 4b) revealed a broad endothermic peak at 112.69°C (ΔH0253.62 J/g) which indicates dehydration process and another peak at 265.43°C (ΔH060.40 J/g) corelatable to decomposition of β-CD (14,15). The physical mixture of LOR and β-CD was an additive thermogram ( Fig.…”

Characterization and In Vitro Evaluation of the Complexes of Posaconazole with β- and 2,6-di-O-methyl-β-cyclodextrin

“…The cyclodextrin (CD) inclusion complex is highly efficient in enhancing water solubility and dissolution of hydrophobic drugs (12)(13)(14). CDs, which are macrocyclic oligosaccharides derived from starch, are composed of glucose units linked by α-1,4-glycosidic bonds in a cyclic manner (15).…”