Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers—A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs
The present study focused on a new formulation approach to improving the solubility of drugs with poor aqueous solubility. A hot melt extrusion (HME) process was applied to prepare drug-loaded solid self-nanoemulsifying drug delivery systems (S-SNEDDS) by co-extrusion of liquid SNEDDS (L-SNEDDS) and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/9/1135 |
| _version_ | 1797483714689630208 |
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| author | Fabian-Pascal Schmied Alexander Bernhardt Sandra Klein |
| author_facet | Fabian-Pascal Schmied Alexander Bernhardt Sandra Klein |
| author_sort | Fabian-Pascal Schmied |
| collection | DOAJ |
| description | The present study focused on a new formulation approach to improving the solubility of drugs with poor aqueous solubility. A hot melt extrusion (HME) process was applied to prepare drug-loaded solid self-nanoemulsifying drug delivery systems (S-SNEDDS) by co-extrusion of liquid SNEDDS (L-SNEDDS) and different polymeric carriers. Experiments were performed with L-SNEDDS formulations containing celecoxib, efavirenz or fenofibrate as model drugs. A major objective was to identify a polymeric carrier and process parameters that would enable the preparation of stable S-SNEDDS without impairing the release behavior and storage stability of the L-SNEDDS used and, if possible, even improving them further. In addition to commercially available (co)polymers already used in the field of HME, a particular focus was on the evaluation of different variants of a recently developed aminomethacrylate-based copolymer (ModE) that differed in M<sub>w</sub>. Immediately after preparation, the L-SNEDDS and S-SNEDDS formulations were tested for amorphicity by differential scanning calorimetry. Furthermore, solubility and dissolution tests were performed. In addition, the storage stability was investigated at 30 °C/65% RH over a period of three and six months, respectively. In all cases, amorphous formulations were obtained and, especially for the model drug celecoxib, S-SNEDDS were developed that maintained the rapid and complete drug release of the underlying L-SNEDDS even over an extended storage period. Overall, the data obtained in this study suggest that the presented S-SNEDDS approach is very promising, provided that drug-loaded L-SNEDDS are co-processed with a suitable polymeric carrier. In the case of celecoxib, the E-173 variant of the novel ModE copolymer proved to be a novel polymeric carrier with great potential for application in S-SNEDDS. The presented approach will, therefore, be pursued in future studies to establish S-SNEDDS as an alternative formulation to other amorphous systems. |
| first_indexed | 2024-03-09T22:50:59Z |
| format | Article |
| id | doaj.art-15a5043eed09450aa025a03a56dcec3d |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:50:59Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-15a5043eed09450aa025a03a56dcec3d2023-11-23T18:19:17ZengMDPI AGPharmaceuticals1424-82472022-09-01159113510.3390/ph15091135Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers—A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble DrugsFabian-Pascal Schmied0Alexander Bernhardt1Sandra Klein2Institute of Biopharmaceutics and Pharmaceutical Technology, Department of Pharmacy, University of Greifswald, Felix-Hausdorff-Straße 3, 17489 Greifswald, GermanyResearch, Development & Innovation, Evonik Operations GmbH, Kirschenallee, 64293 Darmstadt, GermanyInstitute of Biopharmaceutics and Pharmaceutical Technology, Department of Pharmacy, University of Greifswald, Felix-Hausdorff-Straße 3, 17489 Greifswald, GermanyThe present study focused on a new formulation approach to improving the solubility of drugs with poor aqueous solubility. A hot melt extrusion (HME) process was applied to prepare drug-loaded solid self-nanoemulsifying drug delivery systems (S-SNEDDS) by co-extrusion of liquid SNEDDS (L-SNEDDS) and different polymeric carriers. Experiments were performed with L-SNEDDS formulations containing celecoxib, efavirenz or fenofibrate as model drugs. A major objective was to identify a polymeric carrier and process parameters that would enable the preparation of stable S-SNEDDS without impairing the release behavior and storage stability of the L-SNEDDS used and, if possible, even improving them further. In addition to commercially available (co)polymers already used in the field of HME, a particular focus was on the evaluation of different variants of a recently developed aminomethacrylate-based copolymer (ModE) that differed in M<sub>w</sub>. Immediately after preparation, the L-SNEDDS and S-SNEDDS formulations were tested for amorphicity by differential scanning calorimetry. Furthermore, solubility and dissolution tests were performed. In addition, the storage stability was investigated at 30 °C/65% RH over a period of three and six months, respectively. In all cases, amorphous formulations were obtained and, especially for the model drug celecoxib, S-SNEDDS were developed that maintained the rapid and complete drug release of the underlying L-SNEDDS even over an extended storage period. Overall, the data obtained in this study suggest that the presented S-SNEDDS approach is very promising, provided that drug-loaded L-SNEDDS are co-processed with a suitable polymeric carrier. In the case of celecoxib, the E-173 variant of the novel ModE copolymer proved to be a novel polymeric carrier with great potential for application in S-SNEDDS. The presented approach will, therefore, be pursued in future studies to establish S-SNEDDS as an alternative formulation to other amorphous systems.https://www.mdpi.com/1424-8247/15/9/1135copolymeramorphous formulationspoorly soluble drugdrug releasehot melt extrusionnanoemulsion |
| spellingShingle | Fabian-Pascal Schmied Alexander Bernhardt Sandra Klein Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers—A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs Pharmaceuticals copolymer amorphous formulations poorly soluble drug drug release hot melt extrusion nanoemulsion |
| title | Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers—A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs |
| title_full | Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers—A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs |
| title_fullStr | Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers—A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs |
| title_full_unstemmed | Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers—A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs |
| title_short | Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers—A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs |
| title_sort | preparation of solid self nanoemulsifying drug delivery systems s snedds by co extrusion of liquid snedds and polymeric carriers a new and promising formulation approach to improve the solubility of poorly water soluble drugs |
| topic | copolymer amorphous formulations poorly soluble drug drug release hot melt extrusion nanoemulsion |
| url | https://www.mdpi.com/1424-8247/15/9/1135 |
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