Zinc cross-linked hydroxamated alginates for pulsed drug release

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.

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

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

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

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

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

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