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A Novel Approach in Distinguishing Between Role of Hydrodynamics and Mechanical Stresses Similar to Contraction Forces of GI Tract on Drug Release from Modified Release Dosage Forms

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Abstract

The objective of this study was to determine the influence of mechanical stresses simulating gastrointestinal contraction forces of 2.0 N (stomach) and 1.2 N (intestine) on the gel properties and drug release characteristics from sustained release swelling and eroding hydrophilic matrices during dissolution studies. Two batches of tetracycline-sustained release tablets containing hydroxypropyl methyl cellulose (HPMC) were manufactured and subjected to USP apparatus II (pH 2.2 buffer) dissolution studies. Hydrated tablets were periodically removed, placed in a petri dish, and multiple times (six cycle) compressed with a flat-ended probe (diameter 1.3 cm) on a texture analyzer at preprogrammed force of either 2.0 or 1.2 N to determine force-distance profiles and changes in drug release rate. The calculated similarity factor values showed dissimilar dissolution profiles using standard dissolution profile as a reference. The similarity factor (f 2) values were especially lower than 50 at 2.0 N and, when profiles between the two batches compressed at 1.2 and 2.0 N, were compared with each other. The changes in dissolution pattern and release rate were significantly different after 4 h of dissolution. At 8 h, tablets were fully hydrated and no force could be detected by the probe, indicating a very soft gel matrix. It appears that the contraction forces in the stomach and intestine are capable of altering drug release from modified release hydrophilic matrices during transit in the human GI tract. Accounting for these forces during dissolution can enhance predictions of in vivo drug release, achieve better in vitro and in vivo correlation, introduce improvement in dissolution methods, and better understand the critical quality attributes (CQAs) and factors in quality by design (QbD) during the product development process.

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ACKNOWLEDGMENTS

The authors would like to acknowledge Ms. Zheng Lu for assisting in texture analysis work.

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Authors and Affiliations

  1. Metrics, Inc., 1240 Sugg Parkway, Greenville, North Carolina, 27834, USA

    Majde Takieddin

  2. School of Pharmacy, Temple University, 3307 North Broad Street, Philadelphia, Pennsylvania, 19140, USA

    Reza Fassihi

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  1. Majde Takieddin
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  2. Reza Fassihi
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Correspondence to Reza Fassihi.

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Dedication

This work is dedicated to Professor M.R. Hojat, Department of Psychiatry and Human Behavior, and the Director of Jefferson Longitudinal Study, on the occasion of his 66th birthday. He is one of the pioneers in the development of the scales that measure aspects of professionalism in medicine including collaborations between physician, nurse, and pharmacist.

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Takieddin, M., Fassihi, R. A Novel Approach in Distinguishing Between Role of Hydrodynamics and Mechanical Stresses Similar to Contraction Forces of GI Tract on Drug Release from Modified Release Dosage Forms. AAPS PharmSciTech 16, 278–283 (2015). https://doi.org/10.1208/s12249-014-0225-5

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