Dual Activity of Hydroxypropyl-β-Cyclodextrin and Water-Soluble Carriers on the Solubility of Carvedilol

Abstract

Carvedilol (CAR) is a non-selective α and β blocker categorized as class II drug with low water solubility. Several recent studies have investigated ways to overcome this problem. The aim of the present study was to combine two of these methods: the inclusion complex using hydroxypropyl-β-cyclodextrin (HPβCD) with solid dispersion using two carriers: Poloxamer 188 (PLX) and Polyvinylpyrrolidone K-30 (PVP) to enhance the solubility, bioavailability, and the stability of CAR. Kneading method was used to prepare CAR-HPβCD inclusion complex (KD). The action of different carriers separately and in combination on Carvedilol solubility was investigated in three series. CAR-carrier and KD-carrier solid dispersions were prepared by solvent evaporation method. In vitro dissolution test was conducted in three different media: double-distilled water (DDW), simulative gastric fluid (SGF), and PBS pH 6.8 (PBS). The interactions between CAR, HPβCD, and different carriers were explored by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffractometry (XRD), and differential scanning colorimetry (DSC). The results showed higher solubility of CAR in KD-PVP solid dispersions up to 70, 25, and 22 fold compared to pure CAR in DDW, SGF, and PBS, respectively. DSC and XRD analyses indicated an improved degree of transformation of CAR in KD-PVP solid dispersion from crystalline to amorphous state. This study provides a new successful combination of two polymers with the dual action of HPβCD and PLX/PVP on water solubility and bioavailability of CAR.

Solid dispersion systems engineered from hydroxypropyl‐β‐cyclodextrin and water‐soluble polymers for enhanced oral bioavailability of nimodipine

“…The chemical reactions that ensued between the inclusion complex and PVP culminated in a decrease in the mass of the compounds. These results are consistent with an earlier report 53 . The various SD PVP solid dispersions had lower peak intensities due to the interactions among the major compounds (ie, NMD, KD, and PVP).…”

“…In the case of PBS, a 19‐fold increase was observed. Several experimental studies have shown similar trends 53 . The relative increase in the dissolution of the ternary systems could be due to its amorphous nature, which has been confirmed by the XRD, DSC, and FTIR study 57 .…”

Amorphous solid dispersions of carvedilol along with pH‐modifiers improved pharmacokinetic properties under hypochlorhydoria

“…This hypothesis is also supported by the difference between the dissolution behavior of CAR‐ASD/CA50 and PM of CAR‐ASD + CA. In the previous reports, solid dispersion systems for CAR have been reported with use of cyclodextrins, porous silica and polyvinylpyrrolidone as carrier materials of solid dispersion (Sharma et al, ; Yuvaraja & Khanam, ; Zoghbi, Geng, & Wang, ). Cyclodextrins has been widely used for the solubility enhancement due to its high solubilization potency; however, it could have the toxic potential to induce tissue irritation and cytotoxicity in gastrointestinal tract after oral administration (Irie & U. K., ).…”

Enhancing the oral bioavailability of baicalein via Solutol® HS15 and Poloxamer 188 mixed micelles system

“…It can self‐assemble into micelles in an aqueous solution because of its amphiphilic nature, where the hydrophobic chain can reserve the drug and the hydrophilic chain acts as a bridge connecting the drug and the aqueous medium. The micelles formed had advantages of high drug loading and excellent physical stability …”

“…The micelles formed had advantages of high drug loading and excellent physical stability. [17,18] In our design, BAI-loaded HS15/F68 mixed micelles (BAI-M) were prepared by thin-film dispersion method ( Figure 2), and the formulation was optimized with the central composite design (CCD) response surface method. The morphology, particle size and zeta potential of the optimized preparation were characterized by transmission electron microscopy (TEM) and dynamic light scattering.…”