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. 2023 Apr 12;28(8):3405.
doi: 10.3390/molecules28083405.

Synthesis and Characterization of Carvedilol-Etched Halloysite Nanotubes Composites with Enhanced Drug Solubility and Dissolution Rate

Lauretta Maggi  1 , Claudia Urru  2 , Valeria Friuli  1 , Chiara Ferrara  3 , Debora Maria Conti  2 , Giovanna Bruni  2 , Doretta Capsoni  2
Affiliations

Synthesis and Characterization of Carvedilol-Etched Halloysite Nanotubes Composites with Enhanced Drug Solubility and Dissolution Rate

Lauretta Maggi et al. Molecules. .

Abstract

Carvedilol is a poorly water-soluble drug employed to treat chronic heart failure. In this study, we synthesize new carvedilol-etched halloysite nanotubes (HNTs) composites to enhance solubility and dissolution rate. The simple and feasible impregnation method is used for carvedilol loading (30-37% weight). Both the etched HNTs (acidic HCl and H2SO4 and alkaline NaOH treatments) and the carvedilol-loaded samples are characterized by various techniques (XRPD, FT-IR, solid-state NMR, SEM, TEM, DSC, and specific surface area). The etching and loading processes do not induce structural changes. The drug and carrier particles are in intimate contact and their morphology is preserved, as demonstrated by TEM images. The 27Al and 13C solid-state NMR and FT-IR findings show that carvedilol interactions involve the external siloxane surface, especially the aliphatic carbons, the functional groups, and, by inductive effect, the adjacent aromatic carbons. All the carvedilol-halloysite composites display enhanced dissolution rate, wettability, and solubility, as compared to carvedilol. The best performances are obtained for the carvedilol-halloysite system based on HNTs etched with HCl 8M, which exhibits the highest value of specific surface area (91 m2 g-1). The composites make the drug dissolution independent of the environmental conditions of the gastrointestinal tract and its absorption less variable, more predictable, and independent from the pH of the medium.

Keywords: carvedilol; dissolution tests; drug–nanoclay composites; halloysite nanotubes; solid-state NMR.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Molecular structure of carvedilol.
Figure 1
Figure 1
XRPD pattern of H (a), H_HCl_8M (b), H_H2SO4_0.5M (c), and H_NaOH_0.5M (d).
Figure 2
Figure 2
XRPD pattern of H (a), CH, (b) CH_HCl_8M (c), CH_H2SO4_0.5M (d) CH_NaOH_0.5M (e), and C (f).
Figure 3
Figure 3
FT-IR spectra of H (a), H_HCl_8M (b), H_H2SO4_0.5M (c), and H_NaOH_0.5M (d) in 4000–2000 cm−1 (I) and 2000–600 cm−1 (II) wavenumber ranges.
Figure 4
Figure 4
FT-IR spectra of CH_NaOH_0.5M (a), CH_H2SO4_0.5M (b), CH_HCl_8M (c), CH (d), H (e), and C (f) in 4000–2000 cm−1 (I) and 2000–600 cm−1 (II) wavenumber ranges.
Figure 5
Figure 5
The 13C NMR spectra of CH_H2SO4_0.5M (a), CH_HCl_8M (b), CH (c), and C (d) with attribution for the C sample in the 200-0 ppm range (I) and zoom in the 155-130 ppm range (II) and in the 75–30 ppm range (III) to highlight the regions presenting the more significant changes. The symbol * marks a spinning sideband.
Figure 6
Figure 6
SEM images at 10 kX magnification of H (a), H_H2SO4_0.5M (b), H_HCl_8M (c), and H_NaOH_0.5M (d).
Figure 7
Figure 7
SEM images at 3 kX magnification of C (a), CH (b), CH_HCl_8M (c), CH_H2SO4_0.5M (d), and CH_NaOH_0.5M (e).
Figure 8
Figure 8
TEM images at 100 kX magnification of H (a), H_HCl_8M (b), H_H2SO4_0.5M (c), and H_NaOH_0.5M (d).
Figure 9
Figure 9
TEM images at 100 kX magnification of C (a), CH (b), CH_HCl_8M (c), CH_H2SO4_0.5M (d), and CH_NaOH_0.5M (e).
Figure 10
Figure 10
DSC thermograms of H (a), CH (b), CH_HCl_8M (c), CH_H2SO4_0.5M (d), CH_NaOH_0.5M (e), and C (f).
Figure 11
Figure 11
Dissolution profiles of C, CH, CH_HCl_8M, CH_H2SO4_0.5M, and CH_NaOH_0.5M at pH 1.45 (a) according to USP monograph, in which the drug is more soluble; at pH 4.5 (b), simulating gastric fed conditions; pH 6.8 (c), simulating intestinal environment and deionized water (d).
Figure 12
Figure 12
Contact angle (deg) measured on C alone and CH, CH_HCl_8M, and CH_H2SO4_0.5M using different wetting fluids at pH 1.45 (a) (USP monograph), in which the drug is more soluble; at pH 4.5 (b), simulating gastric fed conditions; pH 6.8 (c), simulating intestinal environment and deionized water (d).
See this image and copyright information in PMC

References

    1. Good D.J., Rodríguez-Hornedo N. Solubility Advantage of Pharmaceutical Cocrystals. Cryst. Growth Des. 2009;9:2252–2264. doi: 10.1021/cg801039j. - DOI
    1. Thayer J.F., Yamamoto S.S., Brosschot J.F. The Relationship of Autonomic Imbalance, Heart Rate Variability and Cardiovascular Disease Risk Factors. Int. J. Cardiol. 2010;141:122–131. doi: 10.1016/j.ijcard.2009.09.543. - DOI - PubMed
    1. Kumar S., Singh P. Various Techniques for Solubility Enhancement: An Overview. Pharma Innov. 2016;5:23–28.
    1. Braga D., Grepioni F., Maini L., Polito M. Crystal Polymorphism and Multiple Crystal Forms. In: Hosseini M.W., editor. Molecular Networks. Springer; Berlin/Heidelberg, Germany: 2009. pp. 87–95. Structure and Bonding.
    1. Lu J., Li Z., Jiang X. Polymorphism of Pharmaceutical Molecules: Perspectives on Nucleation. Front. Chem. Sci. Eng. 2010;4:37–44. doi: 10.1007/s11705-009-0294-2. - DOI

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