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  • Title: A novel controlled drug delivery system based on pH-responsive hydrogels included in soft gelatin capsules.
    Author: Frutos G, Prior-Cabanillas A, París R, Quijada-Garrido I.
    Journal: Acta Biomater; 2010 Dec; 6(12):4650-6. PubMed ID: 20643229.
    Abstract:
    pH-sensitive hydrogels based on methacrylic acid (MAA) and poly(ethylene glycol) macromonomer (PEGMEMA) entrapping diltiazem hydrochloride (DIL·HCl) were synthesized inside soft gelatin capsules for use as a new dosage form for oral drug administration. Different monomer compositions were used to evaluate their swelling and release behavior in two media: at low pH, simulating the acid pH of the stomach, and at pH 7, simulating the higher pH environment of the intestine. Both the swelling process and DIL·HCl release strongly depended on pH and monomer composition. Hydrogels with intermediate compositions showed diminished DIL·HCl release at pH 1.2. This fact was related to the formation of an impermeable outer skin, observed by magnetic resonance imaging (MRI). At pH 7 similar shaped release profiles were found for the four hydrogel compositions under investigation. At this neutral pH slow protonation of the carboxylate groups of MAA led to a swelling front and a dry core, also observed by MRI. As a consequence of this anomalous swelling, release curves exhibited a long period of zero order kinetics. This shows that the system could be a suitable candidate to develop a zero order release dosage form for oral administration of DIL·HCl. The swelling and dissolution processes were analyzed by different mathematical approaches.
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