Formulation and Bioequivalence Evaluation of a Miniaturized Fexofenadine Hydrochloride Tablet
<b>Background:</b> Fexofenadine hydrochloride (FEX) is widely used to treat allergic rhinitis. However, poor solubility, high cohesiveness, and risk of polymorphic transformation present significant formulation challenges. Conventional FEX tablet formulations are large and may pose swall...
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2025-06-01
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| author | Woo-Yul Song Chang-Soo Han Won-Sang Yu Jae-Won Jang Gyoung-Won Kim Yoo-Shin Jeon Young-Jin Kim So-Jeong Jeong Ji-Hyun Kang Dong-Wook Kim Yun-Sang Park Chun-Woong Park |
| author_facet | Woo-Yul Song Chang-Soo Han Won-Sang Yu Jae-Won Jang Gyoung-Won Kim Yoo-Shin Jeon Young-Jin Kim So-Jeong Jeong Ji-Hyun Kang Dong-Wook Kim Yun-Sang Park Chun-Woong Park |
| author_sort | Woo-Yul Song |
| collection | DOAJ |
| description | <b>Background:</b> Fexofenadine hydrochloride (FEX) is widely used to treat allergic rhinitis. However, poor solubility, high cohesiveness, and risk of polymorphic transformation present significant formulation challenges. Conventional FEX tablet formulations are large and may pose swallowing difficulties for patients with dysphagia. Therefore, a miniaturized FEX tablet that maintained bioequivalence with the marketed product was developed. <b>Methods:</b> An organic solvent-based binder and porous carrier enhanced solubility, flowability, and process efficiency. The formulation was optimized using a design of experiments approach to assess the effects of tablet size and porous carrier incorporation on dissolution and residual solvent content. Scale-up feasibility was evaluated using Froude number-based process optimization, and stability studies were conducted under accelerated conditions (40 °C and 75% relative humidity) to ensure long-term formulation robustness. <b>Results:</b> The miniaturized tablet exhibited dissolution at pH 4.0 and pH 6.8 equivalent to that of the reference product, whereas a faster dissolution rate was observed at pH 1.2. No significant changes were observed in the dissolution rate, crystalline structure, or impurity levels over six months. An in vivo bioequivalence study demonstrated that the test formulation met the bioequivalence criteria, with 90% confidence intervals for the area under the curve and the C<sub>max</sub> falling within the regulatory acceptance range. <b>Conclusions:</b> A miniaturized and commercially viable fexofenadine hydrochloride tablet was developed (44% weight reduction and 50% volume reduction compared to the marketed product). The organic solvent-based binder and porous carrier system improved manufacturing efficiency, stability, and solubility, thereby ensuring compliance with regulatory standards. These findings provide valuable insights into size reduction, solubility enhancement, and large-scale production strategies for the development of future pharmaceutical formulations. |
| format | Article |
| id | doaj-art-89cb47d779ae4b64b312bf32e6384324 |
| institution | OA Journals |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj-art-89cb47d779ae4b64b312bf32e63843242025-08-20T02:21:49ZengMDPI AGPharmaceutics1999-49232025-06-0117675610.3390/pharmaceutics17060756Formulation and Bioequivalence Evaluation of a Miniaturized Fexofenadine Hydrochloride TabletWoo-Yul Song0Chang-Soo Han1Won-Sang Yu2Jae-Won Jang3Gyoung-Won Kim4Yoo-Shin Jeon5Young-Jin Kim6So-Jeong Jeong7Ji-Hyun Kang8Dong-Wook Kim9Yun-Sang Park10Chun-Woong Park11Department of Pharmacy, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Pharmacy, Chungbuk National University, Cheongju 28644, Republic of KoreaYuyu Pharma, Inc., Seoul 04598, Republic of KoreaYuyu Pharma, Inc., Seoul 04598, Republic of KoreaYuyu Pharma, Inc., Seoul 04598, Republic of KoreaYuyu Pharma, Inc., Seoul 04598, Republic of KoreaDepartment of Pharmacy, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Pharmacy, Chungbuk National University, Cheongju 28644, Republic of KoreaDepartment of Pharmacy, Jeonbuk National University, Jeonju 54896, Republic of KoreaDepartment of Pharmacy, Wonkwang University, Iksan-si 54670, Republic of KoreaP2KBio, Cheongju 28160, Republic of KoreaDepartment of Pharmacy, Chungbuk National University, Cheongju 28644, Republic of Korea<b>Background:</b> Fexofenadine hydrochloride (FEX) is widely used to treat allergic rhinitis. However, poor solubility, high cohesiveness, and risk of polymorphic transformation present significant formulation challenges. Conventional FEX tablet formulations are large and may pose swallowing difficulties for patients with dysphagia. Therefore, a miniaturized FEX tablet that maintained bioequivalence with the marketed product was developed. <b>Methods:</b> An organic solvent-based binder and porous carrier enhanced solubility, flowability, and process efficiency. The formulation was optimized using a design of experiments approach to assess the effects of tablet size and porous carrier incorporation on dissolution and residual solvent content. Scale-up feasibility was evaluated using Froude number-based process optimization, and stability studies were conducted under accelerated conditions (40 °C and 75% relative humidity) to ensure long-term formulation robustness. <b>Results:</b> The miniaturized tablet exhibited dissolution at pH 4.0 and pH 6.8 equivalent to that of the reference product, whereas a faster dissolution rate was observed at pH 1.2. No significant changes were observed in the dissolution rate, crystalline structure, or impurity levels over six months. An in vivo bioequivalence study demonstrated that the test formulation met the bioequivalence criteria, with 90% confidence intervals for the area under the curve and the C<sub>max</sub> falling within the regulatory acceptance range. <b>Conclusions:</b> A miniaturized and commercially viable fexofenadine hydrochloride tablet was developed (44% weight reduction and 50% volume reduction compared to the marketed product). The organic solvent-based binder and porous carrier system improved manufacturing efficiency, stability, and solubility, thereby ensuring compliance with regulatory standards. These findings provide valuable insights into size reduction, solubility enhancement, and large-scale production strategies for the development of future pharmaceutical formulations.https://www.mdpi.com/1999-4923/17/6/756miniaturizedorganic solventporous carrierscale-upbioequivalence |
| spellingShingle | Woo-Yul Song Chang-Soo Han Won-Sang Yu Jae-Won Jang Gyoung-Won Kim Yoo-Shin Jeon Young-Jin Kim So-Jeong Jeong Ji-Hyun Kang Dong-Wook Kim Yun-Sang Park Chun-Woong Park Formulation and Bioequivalence Evaluation of a Miniaturized Fexofenadine Hydrochloride Tablet Pharmaceutics miniaturized organic solvent porous carrier scale-up bioequivalence |
| title | Formulation and Bioequivalence Evaluation of a Miniaturized Fexofenadine Hydrochloride Tablet |
| title_full | Formulation and Bioequivalence Evaluation of a Miniaturized Fexofenadine Hydrochloride Tablet |
| title_fullStr | Formulation and Bioequivalence Evaluation of a Miniaturized Fexofenadine Hydrochloride Tablet |
| title_full_unstemmed | Formulation and Bioequivalence Evaluation of a Miniaturized Fexofenadine Hydrochloride Tablet |
| title_short | Formulation and Bioequivalence Evaluation of a Miniaturized Fexofenadine Hydrochloride Tablet |
| title_sort | formulation and bioequivalence evaluation of a miniaturized fexofenadine hydrochloride tablet |
| topic | miniaturized organic solvent porous carrier scale-up bioequivalence |
| url | https://www.mdpi.com/1999-4923/17/6/756 |
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