Evaluation of Drug–Polymer and Drug–Drug Interaction in Cellulosic Multi-Drug Delivery Matrices
Multi-drug delivery systems have gained increasing interest from the pharmaceutical industry. Alongside this is the interest in amorphous solid dispersions as an approach to achieve effective oral delivery of compounds with solubility-limited bioavailability. Despite this, there is limited informati...
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2025-01-01
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| author | Abdullah Isreb Mohamed A. Alhnan Abdulrahman Mkia Khaled Al-Jammal Abdallah Yaghi Enoche Florence Oga Peter Timmins Michael Bonner Robert T. Forbes |
| author_facet | Abdullah Isreb Mohamed A. Alhnan Abdulrahman Mkia Khaled Al-Jammal Abdallah Yaghi Enoche Florence Oga Peter Timmins Michael Bonner Robert T. Forbes |
| author_sort | Abdullah Isreb |
| collection | DOAJ |
| description | Multi-drug delivery systems have gained increasing interest from the pharmaceutical industry. Alongside this is the interest in amorphous solid dispersions as an approach to achieve effective oral delivery of compounds with solubility-limited bioavailability. Despite this, there is limited information regarding predicting the behavior of two or more drugs (in amorphous forms) in a polymeric carrier and whether molecular interactions between the compounds, between each compound, and if the polymer have any effect on the physical properties of the system. This work studies the interaction between model drug combinations (two of ibuprofen, malonic acid, flurbiprofen, or naproxen) dispersed in a polymeric matrix of hypromellose acetate succinate (HPMCAS) using a solvent evaporation technique. Hildebrand and Hansen calculations were used to predict the miscibility of compounds as long as the difference in their solubility parameter values was not greater than 7 MPa<sup>1/2</sup>. It was observed that the selected APIs (malonic acid, ibuprofen, naproxen, and flurbiprofen) were miscible within the formed polymeric matrix. Adding the API caused depression in the Tg of the polymer to certain concentrations (17%, 23%, 13%) for polymeric matrices loaded with malonic acid, ibuprofen, and naproxen, respectively. Above this, large crystals started to form, and phase separation was seen. Adding two APIs to the same matrix resulted in reducing the saturation concentration of one of the APIs. A trend was observed and linked to Hildebrand and Hansen solubility parameters (HSP). |
| format | Article |
| id | doaj-art-c41d559583084a948bb3edc7c9e8fac3 |
| institution | DOAJ |
| issn | 2409-9279 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Methods and Protocols |
| spelling | doaj-art-c41d559583084a948bb3edc7c9e8fac32025-08-20T03:12:22ZengMDPI AGMethods and Protocols2409-92792025-01-0181410.3390/mps8010004Evaluation of Drug–Polymer and Drug–Drug Interaction in Cellulosic Multi-Drug Delivery MatricesAbdullah Isreb0Mohamed A. Alhnan1Abdulrahman Mkia2Khaled Al-Jammal3Abdallah Yaghi4Enoche Florence Oga5Peter Timmins6Michael Bonner7Robert T. Forbes8Department of Clinical Sciences, Liverpool John Moores University, Liverpool L3 3AF, UKCentre for Pharmaceutical Medicine Research, Institute of Pharmaceutical Science, King’s College London, London WC2R 2LS, UKDepartment of Biotechnology, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman, 19328, JordanSGS Quay Pharmaceuticals Ltd., Quay House, 28 Parkway, Deeside Industrial Park, Deeside CH5 2NS, UKInformation School, University of Sheffield, Sheffield S10 2AH, UKDepartment of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UKDepartment of Pharmacy, University of Huddersfield, Huddersfield HD1 3DH, UKDepartment of Life Sciences, University of Bradford, Bradford BD7 1DP, UKDepartment of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UKMulti-drug delivery systems have gained increasing interest from the pharmaceutical industry. Alongside this is the interest in amorphous solid dispersions as an approach to achieve effective oral delivery of compounds with solubility-limited bioavailability. Despite this, there is limited information regarding predicting the behavior of two or more drugs (in amorphous forms) in a polymeric carrier and whether molecular interactions between the compounds, between each compound, and if the polymer have any effect on the physical properties of the system. This work studies the interaction between model drug combinations (two of ibuprofen, malonic acid, flurbiprofen, or naproxen) dispersed in a polymeric matrix of hypromellose acetate succinate (HPMCAS) using a solvent evaporation technique. Hildebrand and Hansen calculations were used to predict the miscibility of compounds as long as the difference in their solubility parameter values was not greater than 7 MPa<sup>1/2</sup>. It was observed that the selected APIs (malonic acid, ibuprofen, naproxen, and flurbiprofen) were miscible within the formed polymeric matrix. Adding the API caused depression in the Tg of the polymer to certain concentrations (17%, 23%, 13%) for polymeric matrices loaded with malonic acid, ibuprofen, and naproxen, respectively. Above this, large crystals started to form, and phase separation was seen. Adding two APIs to the same matrix resulted in reducing the saturation concentration of one of the APIs. A trend was observed and linked to Hildebrand and Hansen solubility parameters (HSP).https://www.mdpi.com/2409-9279/8/1/4Hansen solubility parameterssolid dispersionmulti-drug delivery systemdrug interactionsubstitution in solid matrixdrug–polymer interaction |
| spellingShingle | Abdullah Isreb Mohamed A. Alhnan Abdulrahman Mkia Khaled Al-Jammal Abdallah Yaghi Enoche Florence Oga Peter Timmins Michael Bonner Robert T. Forbes Evaluation of Drug–Polymer and Drug–Drug Interaction in Cellulosic Multi-Drug Delivery Matrices Methods and Protocols Hansen solubility parameters solid dispersion multi-drug delivery system drug interaction substitution in solid matrix drug–polymer interaction |
| title | Evaluation of Drug–Polymer and Drug–Drug Interaction in Cellulosic Multi-Drug Delivery Matrices |
| title_full | Evaluation of Drug–Polymer and Drug–Drug Interaction in Cellulosic Multi-Drug Delivery Matrices |
| title_fullStr | Evaluation of Drug–Polymer and Drug–Drug Interaction in Cellulosic Multi-Drug Delivery Matrices |
| title_full_unstemmed | Evaluation of Drug–Polymer and Drug–Drug Interaction in Cellulosic Multi-Drug Delivery Matrices |
| title_short | Evaluation of Drug–Polymer and Drug–Drug Interaction in Cellulosic Multi-Drug Delivery Matrices |
| title_sort | evaluation of drug polymer and drug drug interaction in cellulosic multi drug delivery matrices |
| topic | Hansen solubility parameters solid dispersion multi-drug delivery system drug interaction substitution in solid matrix drug–polymer interaction |
| url | https://www.mdpi.com/2409-9279/8/1/4 |
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