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Design and Evaluation of Hydrophilic Matrix System for pH-Independent Sustained Release of Weakly Acidic Poorly Soluble Drug

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Abstract

The aim of this research was to design and evaluate a hydrophilic matrix system for sustained release of glipizide, a weakly acidic poor soluble drug. A combination of inclusion complexation and microenvironmental pH modification techniques was utilized to improve the dissolution and pH-independent release of glipizide. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as the complexation agent while sodium citrate and magnesium oxide (MgO) were used as model pH modifiers. The hydrophilic matrix tablets were prepared by powder direct compression and evaluated by in vitro dissolution study respectively in pH 6.8 and pH 1.2 dissolution media. The formulations containing MgO exhibited increased cumulative drug release from less than 40% in the reference formulation to 90% within 24 h in acidic media (pH 1.2). The release profile in acidic media was similar to the alkaline media (pH 6.8) with a similarity factor (f2) of 55.0, suggesting the weakening of the effect of pH on the dissolution efficiency of glipizide. The release profile fitted well into the Higuchi model and the dominant mechanism of drug release was Fickian diffusion while case II transport/polymer relaxation occurred. In conclusion, combining inclusion complexation agents and pH modifiers had improved the dissolution of glipizide as well as achieved the pH-independent release profile.

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Funding

This research was supported by Funds of Shenzhen Science and Technology Innovation Commission (Program No. JCYJ20160428091243299).

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Authors and Affiliations

  1. Guangdong Key Laboratory of Pharmaceutical New Dosage Form, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, China

    Huang Jinheng, Lin Huaqing, Peng Bingxin, Huang Qianfeng & Shuai Fangzhou

  2. Shenzhen Shiyan People’s Hospital, Shenzhen, China

    Xie Yanxian

Authors
  1. Huang Jinheng
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  2. Lin Huaqing
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  3. Peng Bingxin
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  4. Huang Qianfeng
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Correspondence to Lin Huaqing.

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Huang, J., Lin, H., Peng, B. et al. Design and Evaluation of Hydrophilic Matrix System for pH-Independent Sustained Release of Weakly Acidic Poorly Soluble Drug. AAPS PharmSciTech 19, 2144–2154 (2018). https://doi.org/10.1208/s12249-018-1008-1

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  • DOI: https://doi.org/10.1208/s12249-018-1008-1

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