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. 2013 Oct;3(4):194-202.
doi: 10.4103/2230-973X.121292.

Zinc cross-linked hydroxamated alginates for pulsed drug release

Neha S Raut  1 , Prasad R Deshmukh  1 , Milind J Umekar  1 , Nandkishor R Kotagale  1
Affiliations

Zinc cross-linked hydroxamated alginates for pulsed drug release

Neha S Raut et al. Int J Pharm Investig. 2013 Oct.

Abstract

Introduction: Alginates can be tailored chemically to improve solubility, physicochemical, and biological properties and its complexation with metal ion is useful for controlling the drug release.

Materials and methods: Synthesized N,O-dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were subsequently complexed with zinc to form beads. Hydroxamation of sodium alginate was confirmed by Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC).

Results: The synthesized polymeric material exhibited reduced aqueous, HCl and NaOH solubility. The hydroxamated derivatives demonstrated pulsed release where change in pH of the dissolution medium stimulated the atenolol release.

Conclusion: Atenolol loaded Zn cross-linked polymeric beads demonstrated the sustained the plasma drug levels with increased half-life. Although the synthesized derivatives greatly altered the aqueous solubility of sodium alginate, no significant differences in in vitro and in vivo atenolol release behavior amongst the N,O-dimethyl, N-methyl, or N-Benzyl hydroxylamine derivatives of sodium alginate were observed.

Keywords: Atenolol; hydroxylamine derivatives; metal-polymer cross-linked beads; pulsatile release; sodium alginate.

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Conflict of interest statement

Conflict of Interest: None declared

Figures

Figure 1
Figure 1
Fourier transform infrared spectroscopy (FTIR) spectra of synthesized hydroxylamine derivatives. A = Sodium alginate, B = N,Odimethyl hydroxamated alginate, C = N-methyl hydroxamated alginate, D = O-benzyl hydroxamated alginate
Figure 2
Figure 2
Differential scanning calorimetry (DSC) thermograms of synthesized hydroxylamine derivatives. A = Sodium alginate, B = N,Odimethyl hydroxamated alginate, C = N-methyl hydroxamated alginate, D = O-benzyl hydroxamated alginate
Figure 3
Figure 3
Scanning electron microscopy (SEM) photographs of atenolol loaded zinc cross-linked beads prepared from: (a) Sodium alginate, (b) N,O-dimethyl hydroxamated alginate (50%), (c) N,O-dimethyl hydroxamated alginate (100%), (d) N-methyl hydroxamated alginate (50%), (e) N-methyl hydroxamated alginate (100%), (f) O-benzyl hydroxamated alginate (50%), (g) O-benzyl hydroxamated alginate (100%)
Figure 4
Figure 4
FTIR spectra of atenolol loaded zinc cross-linked beads prepared from: (a) Sodium alginate. (b) N,O-dimethyl hydroxamated alginate. (c) N-methyl hydroxamated alginate. (d) O-benzyl hydroxamated alginate
Figure 5
Figure 5
In vitro atenolol release zinc cross-linked beads prepared from (a) Sodium alginate; (b) N,O-dimethyl hydroxamated alginate (50%); (c) N,O-dimethyl hydroxamated alginate (100%); (d) N-methyl hydroxamated alginate (50%), (e) N-methyl hydroxamated alginate (100%), (f) O-benzyl hydroxamated alginate (50%), and (g) O-benzyl hydroxamated alginate (100%)
Figure 6
Figure 6
In vivo plasma atenolol concentrations following single oral administration of atenolol loaded zinc cross-linked sodium alginate and its N,O-dimethyl, N-methyl, or N-benzyl hydroxylamine derivatives
See this image and copyright information in PMC

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