Flavonoid-based pH-responsive hydrogels as carrier of unstable drugs in oxidative conditions.

Flavonoid-based pH-responsive hydrogels as carrier of unstable drugs in oxidative conditions.

Pharmaceutical development and technology (2013-12-03)

Umile Gianfranco Spizzirri, Giuseppe Cirillo, Manuela Curcio, Nevio Picci, Francesca Iemma

ABSTRACT

In this study, pH-responsive hydrogels, synthesized by the coupling reaction of polyacrylic acid and catechin, are proposed as carriers of oxidable drugs toward the GI tract. The presence of polyphenolic moieties in the network gives the polymers properties suitable for the release of unstable drugs in oxidative conditions. The characterization of the hydrogels is obtained by means of morphological and physico-chemical analyses, antioxidant assays and evaluation of the swelling behavior in media simulating the gastric (pH 1.0) and the intestinal (pH 7.4) tracts. The hydrogels are tested as pH-responsive carriers in in vitro release studies of folic acid and thiamine, two model drugs easily degraded by oxidative conditions simulated by UV irradiation and t-butyl hydroperoxide treatment, respectively. Results show that catechin-based carriers are able to control the release of drugs at different pH values, giving a remarkable improvement in the stability of the therapeutics.

MATERIALS

Product Number

Brand

Product Description

PHR1372

Supelco

Methanol, Pharmaceutical Secondary Standard; Certified Reference Material

M1775

Sigma-Aldrich

Methanol, Absolute - Acetone free

S2127

Sigma-Aldrich

Sodium carbonate, ReagentPlus^®, ≥99.5%

07102

Sigma-Aldrich

Hydrochloric acid, meets analytical specification of Ph. Eur., BP, NF, fuming, 36.5-38%

07104

Sigma-Aldrich

Hydrochloric acid, puriss., 24.5-26.0%

791768

Sigma-Aldrich

Sodium carbonate, anhydrous, free-flowing, Redi-Dri^™, ACS reagent, ≥99.5%

900503

Sigma-Aldrich

Sodium carbonate, anhydrous, powder or granules, free-flowing, Redi-Dri^™, ACS reagent, ≥99.5%

179337

Sigma-Aldrich

Methanol, ACS reagent, ≥99.8%

900505

Sigma-Aldrich

Sodium carbonate, anhydrous, free-flowing, Redi-Dri^™, ReagentPlus^®, ≥99.5%

900504

Sigma-Aldrich

Sodium carbonate, anhydrous, free-flowing, Redi-Dri^™, ACS reagent (primary standard), 99.95-100.05% dry basis

676780

Sigma-Aldrich

Methanol, ACS reagent, ≥99.8%

13418

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Sodium carbonate, puriss., meets analytical specification of Ph. Eur., BP, NF, FCC, E500, anhydrous, 99.5-100.5% (calc. to the dried substance)

676845

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Diethyl ether, ACS reagent, ≥98.0%, contains ≤2% ethanol and ≤10ppm BHT as inhibitor

33120

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N,N-Dimethylformamide, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.8% (GC)

494488

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N,N-Dimethylformamide, biotech. grade, ≥99.9%

320390

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Methanol, ACS reagent, ≥99.8%

346144

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Diethyl ether, reagent grade, ≥98%, contains ≤2% ethanol and ≤10ppm BHT as inhibitor

345547

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Hydrogen chloride solution, 4.0 M in dioxane

455180

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Hydrogen chloride solution, 2.0 M in diethyl ether

24229

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Methanol, puriss., meets analytical specification of Ph Eur, ≥99.7% (GC)

346136

Sigma-Aldrich

Diethyl ether, ACS reagent, anhydrous, ≥99.0%, contains BHT as inhibitor

24004

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Diethyl ether, puriss., contains ~5 mg/L 2,6-di-tert.-butyl-4-methylphenol as stabilizer, meets analytical specification of Ph. Eur., BP, ≥99.5% (GC)

673811

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Diethyl ether, anhydrous, ACS reagent, ≥99.0%, contains BHT as inhibitor

494437

Sigma-Aldrich

Methanol, BioReagent, ≥99.93%

32203

Sigma-Aldrich

Diethyl ether, contains BHT as inhibitor, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)

294837

Sigma-Aldrich

Hydrogen chloride solution, 1.0 M in diethyl ether