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

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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.

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Abbreviations

CAR:

Carvedilol

HPβCD:

Hydroxypropyl-β-Cyclodextrin

PLX:

Poloxamer 188

PVP:

Polyvinyl pyrrolidone K-30

KD:

CAR-HPβCD inclusion complex

PLX1:

CAR-PLX solid dispersion in the weight ratio 1:1

PLX2:

CAR-PLX solid dispersion in the weight ratio 1:3

PLX3:

CAR-PLX solid dispersion in the weight ratio 1:5

PVP1:

CAR-PVP solid dispersion in the weight ratio 1:1

PVP2:

CAR-PVP solid dispersion in the weight ratio 1:3

PVP3:

CAR-PVP solid dispersion in the weight ratio 1:5

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Authors and Affiliations

  1. Department of Pharmaceutics, China Pharmaceutical University, #639 Longmian Avenue, Jiangning District, Nanjing, 211198, People’s Republic of China

    Abdelmoumin Zoghbi, Tianjiao Geng & Bo Wang

  2. Department of Pharmacy, Ferhat Abbas University, 19000, Setif, Algeria

    Abdelmoumin Zoghbi

Authors
  1. Abdelmoumin Zoghbi
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  2. Tianjiao Geng
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  3. Bo Wang
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Correspondence to Bo Wang.

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Zoghbi, A., Geng, T. & Wang, B. Dual Activity of Hydroxypropyl-β-Cyclodextrin and Water-Soluble Carriers on the Solubility of Carvedilol. AAPS PharmSciTech 18, 2927–2935 (2017). https://doi.org/10.1208/s12249-017-0769-2

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