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Optimization of Chronomodulated Delivery System Coated with a Blend of Ethyl Cellulose and Eudragit L100 by Central Composite Design: In Vitro and In Vivo Evaluation

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Abstract

Introduction

In this study, we present the development of a chronomodulated delivery system consisting of a fast-swelling tablet core containing montelukast sodium coated with a blend of different ratios of ethyl cellulose (gastrointestinal tract (GIT)-insoluble polymer) and Eudragit L100 (enteric polymer). Montelukast sodium is a leukotriene receptor antagonist commonly prescribed for patients of asthma and allergic rhinitis. Asthma and allergic rhinitis share a common core pathophysiology and have almost similar temporal pattern in their occurrence or exacerbation of their respective symptoms, suggesting a role for chronotherapy.

Methods

The developed formulation was optimized statistically using central composite design to achieve desired release profile. The coated tablets were studied for water uptake, bursting time, and in vitro release study.

Results

The bursting time (lag time) of coated tablet was affected by the pH of buffer, molarity of ions, and concentration of different types of surfactant in dissolution media. With increasing percentage of Eudragit L100 in coating composition, the lag time decreased and release rates significantly increased—could be attributed due to increase in water uptake and polymer leaching. As expected, with increasing coating level, lag time increased and release rate decreased due to the increased diffusion pathways. In vivo study revealed comparative pharmacokinetic profiles of core tablets and pulsatile release tablets (PRTs); however, T max of 2 h for core tablets and 6 h for PRTs were observed.

Conclusion

Thus, designed PRTs were found to be suitable in treating episodic attack of asthma in early morning and associated allergic rhinitis.

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Acknowledgments

The authors are grateful to acknowledge Manipal College of Pharmaceutical Sciences, Manipal University, Manipal for providing infrastructure facility and ICMR, New Delhi, India for financial support.

Conflicts of Interest

Authors have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India

    Om Prakash Ranjan, Usha Y. Nayak & M. Sreenivasa Reddy

  2. Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India

    Swapnil J. Dengale & Prashant B. Musmade

  3. Department of Pharmaceutical Management, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104, Karnataka, India

    Nayanabhirama Udupa

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  1. Om Prakash Ranjan
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  2. Usha Y. Nayak
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  3. M. Sreenivasa Reddy
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  4. Swapnil J. Dengale
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  5. Prashant B. Musmade
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  6. Nayanabhirama Udupa
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Correspondence to M. Sreenivasa Reddy.

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Ranjan, O.P., Nayak, U.Y., Reddy, M.S. et al. Optimization of Chronomodulated Delivery System Coated with a Blend of Ethyl Cellulose and Eudragit L100 by Central Composite Design: In Vitro and In Vivo Evaluation. J Pharm Innov 9, 95–105 (2014). https://doi.org/10.1007/s12247-014-9176-3

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  • DOI: https://doi.org/10.1007/s12247-014-9176-3

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