Preparation of Hot-Melt-Extruded Solid Dispersion Based on Pre-Formulation Strategies and Its Enhanced Therapeutic Efficacy
In this study, an amorphous solid dispersion containing the poorly water-soluble drug, bisacodyl, was prepared by hot-melt extrusion to enhance its therapeutic efficacy. First, the miscibility and interaction between the drug and polymer were investigated as pre-formulation strategies using various...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/12/2704 |
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| author | Seon-Kwang Lee Eun-Sol Ha Heejun Park Kyu-Tae Kang Ji-Su Jeong Jeong-Soo Kim In-hwan Baek Min-Soo Kim |
| author_facet | Seon-Kwang Lee Eun-Sol Ha Heejun Park Kyu-Tae Kang Ji-Su Jeong Jeong-Soo Kim In-hwan Baek Min-Soo Kim |
| author_sort | Seon-Kwang Lee |
| collection | DOAJ |
| description | In this study, an amorphous solid dispersion containing the poorly water-soluble drug, bisacodyl, was prepared by hot-melt extrusion to enhance its therapeutic efficacy. First, the miscibility and interaction between the drug and polymer were investigated as pre-formulation strategies using various analytical approaches to obtain information for selecting a suitable polymer. Based on the calculation of the Hansen solubility parameter and the identification of the single glass transition temperature (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>T</mi><mi>g</mi></msub></mrow></semantics></math></inline-formula>), the miscibility between bisacodyl and all the investigated polymers was confirmed. Additionally, the drug–polymer molecular interaction was identified based on the comprehensive results of dynamic vapor sorption (DVS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and a comparison of the predicted and experimental values of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>T</mi><mi>g</mi></msub></mrow></semantics></math></inline-formula>. In particular, the hydroxypropyl methylcellulose (HPMC)-based solid dispersions, which exhibited large deviation between the calculated and experimental values of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>T</mi><mi>g</mi></msub></mrow></semantics></math></inline-formula> and superior physical stability after DVS experiments, were selected as the most appropriate solubilized bisacodyl formulations due to the excellent inhibitory effects on precipitation based on the results of the non-sink dissolution test. Furthermore, it was shown that the enteric-coated tablets containing HPMC–bisacodyl at a 1:4 ratio (<i>w</i>/<i>w</i>) had significantly improved in vivo therapeutic laxative efficacy compared to preparations containing un-solubilized raw bisacodyl in constipation-induced rabbits. Therefore, it was concluded that the pre-formulation strategy, using several analyses and approaches, was successfully applied in this study to investigate the miscibility and interaction of drug–polymer systems, hence resulting in the manufacture of favorable solid dispersions with favorable in vitro and in vivo performances using hot-melt extrusion processes. |
| first_indexed | 2024-03-08T20:27:17Z |
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| id | doaj.art-b43364c40a8e453d9a89c6247158fc7c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-08T20:27:17Z |
| publishDate | 2023-11-01 |
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| spelling | doaj.art-b43364c40a8e453d9a89c6247158fc7c2023-12-22T14:32:03ZengMDPI AGPharmaceutics1999-49232023-11-011512270410.3390/pharmaceutics15122704Preparation of Hot-Melt-Extruded Solid Dispersion Based on Pre-Formulation Strategies and Its Enhanced Therapeutic EfficacySeon-Kwang Lee0Eun-Sol Ha1Heejun Park2Kyu-Tae Kang3Ji-Su Jeong4Jeong-Soo Kim5In-hwan Baek6Min-Soo Kim7College of Pharmacy, Pusan National University, 63 Busandaehak-ro, Geumjeong-gu, Busan 46241, Republic of KoreaCollege of Pharmacy, Pusan National University, 63 Busandaehak-ro, Geumjeong-gu, Busan 46241, Republic of KoreaCollege of Pharmacy, Duksung Women’s University, 33, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of KoreaCollege of Pharmacy, Duksung Women’s University, 33, Samyangro 144-gil, Dobong-gu, Seoul 01369, Republic of KoreaCollege of Pharmacy, Pusan National University, 63 Busandaehak-ro, Geumjeong-gu, Busan 46241, Republic of KoreaDong-A ST Co., Ltd., Giheung-gu, Yongin 17073, Republic of KoreaCollege of Pharmacy, Kyungsung University, 309, Suyeong-ro, Nam-gu, Busan 48434, Republic of KoreaCollege of Pharmacy, Pusan National University, 63 Busandaehak-ro, Geumjeong-gu, Busan 46241, Republic of KoreaIn this study, an amorphous solid dispersion containing the poorly water-soluble drug, bisacodyl, was prepared by hot-melt extrusion to enhance its therapeutic efficacy. First, the miscibility and interaction between the drug and polymer were investigated as pre-formulation strategies using various analytical approaches to obtain information for selecting a suitable polymer. Based on the calculation of the Hansen solubility parameter and the identification of the single glass transition temperature (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>T</mi><mi>g</mi></msub></mrow></semantics></math></inline-formula>), the miscibility between bisacodyl and all the investigated polymers was confirmed. Additionally, the drug–polymer molecular interaction was identified based on the comprehensive results of dynamic vapor sorption (DVS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and a comparison of the predicted and experimental values of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>T</mi><mi>g</mi></msub></mrow></semantics></math></inline-formula>. In particular, the hydroxypropyl methylcellulose (HPMC)-based solid dispersions, which exhibited large deviation between the calculated and experimental values of <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><msub><mi>T</mi><mi>g</mi></msub></mrow></semantics></math></inline-formula> and superior physical stability after DVS experiments, were selected as the most appropriate solubilized bisacodyl formulations due to the excellent inhibitory effects on precipitation based on the results of the non-sink dissolution test. Furthermore, it was shown that the enteric-coated tablets containing HPMC–bisacodyl at a 1:4 ratio (<i>w</i>/<i>w</i>) had significantly improved in vivo therapeutic laxative efficacy compared to preparations containing un-solubilized raw bisacodyl in constipation-induced rabbits. Therefore, it was concluded that the pre-formulation strategy, using several analyses and approaches, was successfully applied in this study to investigate the miscibility and interaction of drug–polymer systems, hence resulting in the manufacture of favorable solid dispersions with favorable in vitro and in vivo performances using hot-melt extrusion processes.https://www.mdpi.com/1999-4923/15/12/2704hot-melt extrusionsolid dispersionmiscibilitymolecular interactionbisacodylin vivo efficacy |
| spellingShingle | Seon-Kwang Lee Eun-Sol Ha Heejun Park Kyu-Tae Kang Ji-Su Jeong Jeong-Soo Kim In-hwan Baek Min-Soo Kim Preparation of Hot-Melt-Extruded Solid Dispersion Based on Pre-Formulation Strategies and Its Enhanced Therapeutic Efficacy Pharmaceutics hot-melt extrusion solid dispersion miscibility molecular interaction bisacodyl in vivo efficacy |
| title | Preparation of Hot-Melt-Extruded Solid Dispersion Based on Pre-Formulation Strategies and Its Enhanced Therapeutic Efficacy |
| title_full | Preparation of Hot-Melt-Extruded Solid Dispersion Based on Pre-Formulation Strategies and Its Enhanced Therapeutic Efficacy |
| title_fullStr | Preparation of Hot-Melt-Extruded Solid Dispersion Based on Pre-Formulation Strategies and Its Enhanced Therapeutic Efficacy |
| title_full_unstemmed | Preparation of Hot-Melt-Extruded Solid Dispersion Based on Pre-Formulation Strategies and Its Enhanced Therapeutic Efficacy |
| title_short | Preparation of Hot-Melt-Extruded Solid Dispersion Based on Pre-Formulation Strategies and Its Enhanced Therapeutic Efficacy |
| title_sort | preparation of hot melt extruded solid dispersion based on pre formulation strategies and its enhanced therapeutic efficacy |
| topic | hot-melt extrusion solid dispersion miscibility molecular interaction bisacodyl in vivo efficacy |
| url | https://www.mdpi.com/1999-4923/15/12/2704 |
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