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Preparation and characterization of pH-sensitive methyl methacrylate-g-starch/hydroxypropylated starch hydrogels: in vitro and in vivo study on release of esomeprazole magnesium

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Abstract

In the present study, novel hydrogels were prepared through graft copolymerization of methyl methacrylate onto starch and hydroxypropylated starch for intestinal drug delivery. The successful grafting has been confirmed by FTIR, NMR spectroscopy, and elemental analysis. Morphological examination of copolymeric hydrogels by scanning electron microscopy (SEM) confirms the macroporous nature of the copolymers. The high decomposition temperature was observed in thermograms indicating the thermal stability of the hydrogels. To attain a hydrogel with maximum percent graft yield, the impact of reaction variables like concentration of ceric ammonium nitrate as initiator and methyl methacrylate as monomer were consistently optimized. X-ray powder diffraction and differential scanning calorimetric analysis supported the successful entrapment of the drug moiety (esomeprazole magnesium; proton pump inhibitor) within the hydrogel network. Drug encapsulation efficiency of optimized hydrogels was found to be >78 %. Furthermore, swelling capacity of copolymeric hydrogels exhibited a pH-responsive behavior which makes the synthesized hydrogels potential candidates for controlled delivery of medicinal agents. In vitro drug release was found to be sustained up to 14 h with 80–90 % drug release in pH 6.8 solution; however, the cumulative release was 40–45 % in pH 1.2. The gastrointestinal transit behavior of optimized hydrogel was determined by gamma scintigraphy, using 99mTc as marker. The amount of radioactive tracer released from the labeled hydrogel was minimal when the hydrogel was in the stomach, whereas it increased as hydrogel reached in intestine. Well-correlated results of in vitro and in vivo analysis proved their controlled release behavior with preferential delivery into alkaline pH environment.

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Acknowledgments

The authors are thankful to their parental institutes for providing the necessary facilities to accomplish the present research work. The authors are grateful to the Director, Spect Radiology Lab, Pune, and the nuclear medicine staff for their cooperation and for providing all the necessary facilities to conduct the gamma scintigraphy study.

Conflict of interest

The authors declared no conflict of interest.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Siksha O Anusandhan University, Bhubaneswar, 751030, India

    Pankaj Kumar & Bharat Bhushan Subudhi

  2. Sahyadri College of Pharmacy, Sangola, Solapur, MS, 413307, India

    Ashok Laxmanrao Ganure

  3. Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi, 221005, India

    Shubhanjali Shukla

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  1. Pankaj Kumar
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  2. Ashok Laxmanrao Ganure
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  3. Bharat Bhushan Subudhi
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  4. Shubhanjali Shukla
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Correspondence to Pankaj Kumar.

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Kumar, P., Ganure, A.L., Subudhi, B.B. et al. Preparation and characterization of pH-sensitive methyl methacrylate-g-starch/hydroxypropylated starch hydrogels: in vitro and in vivo study on release of esomeprazole magnesium. Drug Deliv. and Transl. Res. 5, 243–256 (2015). https://doi.org/10.1007/s13346-015-0221-7

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  • DOI: https://doi.org/10.1007/s13346-015-0221-7

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