A Novel Rheological Method to Assess Drug-Polymer Interactions Regarding Miscibility and Crystallization of Drug in Amorphous Solid Dispersions for Oral Drug Delivery
Solid dispersions provide a key technology to formulate poorly water-soluble drugs, and a main task of early development is appropriate selection of polymer. This study investigates the use of a novel rheology-based approach to evaluate miscibility and interactions of drugs with polymers regarding a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/11/12/625 |
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| author | Georgia Tsakiridou Christos Reppas Martin Kuentz Lida Kalantzi |
| author_facet | Georgia Tsakiridou Christos Reppas Martin Kuentz Lida Kalantzi |
| author_sort | Georgia Tsakiridou |
| collection | DOAJ |
| description | Solid dispersions provide a key technology to formulate poorly water-soluble drugs, and a main task of early development is appropriate selection of polymer. This study investigates the use of a novel rheology-based approach to evaluate miscibility and interactions of drugs with polymers regarding amorphous solid drug dispersions for oral administration. Tacrolimus was used as model drug and hydroxypropyl cellulose, ethylcellulose, Soluplus<sup>®</sup>, polyethyleneglycol 6000, Poloxamer-188 (Koliphor-188), and Eudragit<sup>®</sup> S100 were used as excipients. Solvent-based evaporation methods were used to prepare binary solid dispersions of drug and polymer. Data of the dilute solution viscosimetry were compared with in silico calculations of the Hansen solubility parameter (HSP), as well as phase separation/crystallization data obtained from X-ray diffraction and differential scanning calorimetry. HSP calculations in some cases led to false positive predictions of tacrolimus miscibility with the tested polymers. The novel rheology-based method provided valuable insights into drug-polymer interactions and likely miscibility with polymer. It is a rather fast, inexpensive, and robust analytical approach, which could be used complementary to in silico-based evaluation of polymers in early formulation development, especially in cases of rather large active pharmaceutical ingredients. |
| first_indexed | 2024-04-11T18:00:43Z |
| format | Article |
| id | doaj.art-331d9b69f0644e25be0cfca314efa8a0 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T18:00:43Z |
| publishDate | 2019-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-331d9b69f0644e25be0cfca314efa8a02022-12-22T04:10:29ZengMDPI AGPharmaceutics1999-49232019-11-01111262510.3390/pharmaceutics11120625pharmaceutics11120625A Novel Rheological Method to Assess Drug-Polymer Interactions Regarding Miscibility and Crystallization of Drug in Amorphous Solid Dispersions for Oral Drug DeliveryGeorgia Tsakiridou0Christos Reppas1Martin Kuentz2Lida Kalantzi3Department of Scientific Affairs, Pharmathen S/A, 15125 Marousi, GreeceDepartment of Pharmaceutical Sciences, National and Kapodistrian University of Athens, 15784 Zografou, GreeceInstitute of Pharmaceutical Technology, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, SwitzerlandDepartment of Scientific Affairs, Pharmathen S/A, 15125 Marousi, GreeceSolid dispersions provide a key technology to formulate poorly water-soluble drugs, and a main task of early development is appropriate selection of polymer. This study investigates the use of a novel rheology-based approach to evaluate miscibility and interactions of drugs with polymers regarding amorphous solid drug dispersions for oral administration. Tacrolimus was used as model drug and hydroxypropyl cellulose, ethylcellulose, Soluplus<sup>®</sup>, polyethyleneglycol 6000, Poloxamer-188 (Koliphor-188), and Eudragit<sup>®</sup> S100 were used as excipients. Solvent-based evaporation methods were used to prepare binary solid dispersions of drug and polymer. Data of the dilute solution viscosimetry were compared with in silico calculations of the Hansen solubility parameter (HSP), as well as phase separation/crystallization data obtained from X-ray diffraction and differential scanning calorimetry. HSP calculations in some cases led to false positive predictions of tacrolimus miscibility with the tested polymers. The novel rheology-based method provided valuable insights into drug-polymer interactions and likely miscibility with polymer. It is a rather fast, inexpensive, and robust analytical approach, which could be used complementary to in silico-based evaluation of polymers in early formulation development, especially in cases of rather large active pharmaceutical ingredients.https://www.mdpi.com/1999-4923/11/12/625amorphous solid dispersionspolymer-api miscibilityrheologyhansen solubility parameters |
| spellingShingle | Georgia Tsakiridou Christos Reppas Martin Kuentz Lida Kalantzi A Novel Rheological Method to Assess Drug-Polymer Interactions Regarding Miscibility and Crystallization of Drug in Amorphous Solid Dispersions for Oral Drug Delivery Pharmaceutics amorphous solid dispersions polymer-api miscibility rheology hansen solubility parameters |
| title | A Novel Rheological Method to Assess Drug-Polymer Interactions Regarding Miscibility and Crystallization of Drug in Amorphous Solid Dispersions for Oral Drug Delivery |
| title_full | A Novel Rheological Method to Assess Drug-Polymer Interactions Regarding Miscibility and Crystallization of Drug in Amorphous Solid Dispersions for Oral Drug Delivery |
| title_fullStr | A Novel Rheological Method to Assess Drug-Polymer Interactions Regarding Miscibility and Crystallization of Drug in Amorphous Solid Dispersions for Oral Drug Delivery |
| title_full_unstemmed | A Novel Rheological Method to Assess Drug-Polymer Interactions Regarding Miscibility and Crystallization of Drug in Amorphous Solid Dispersions for Oral Drug Delivery |
| title_short | A Novel Rheological Method to Assess Drug-Polymer Interactions Regarding Miscibility and Crystallization of Drug in Amorphous Solid Dispersions for Oral Drug Delivery |
| title_sort | novel rheological method to assess drug polymer interactions regarding miscibility and crystallization of drug in amorphous solid dispersions for oral drug delivery |
| topic | amorphous solid dispersions polymer-api miscibility rheology hansen solubility parameters |
| url | https://www.mdpi.com/1999-4923/11/12/625 |
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