Computational Amendment of Parenteral In Situ Forming Particulates’ Characteristics: Design of Experiment and PBPK Physiological Modeling
| dc.contributor.author | El Hoffy ,Nada M. | |
| dc.contributor.author | Yacoub , Ahmed S | |
| dc.contributor.author | Ghoneim , Amira M. | |
| dc.contributor.author | Ibrahim , Magdy | |
| dc.contributor.author | Amma, Hussein | |
| dc.contributor.author | Eissa, Nermin | |
| dc.date.accessioned | 2024-02-05T04:48:01Z | |
| dc.date.available | 2024-02-05T04:48:01Z | |
| dc.date.issued | 2023-10 | |
| dc.description | Numerous drug candidates who suffer from poor oral bioavailability or minimal half-life now have a higher therapeutic potential, thanks to the development of innovative drug discovery tools, including genetic engineering, combinatorial chemistry, and high-throughput screening [1]. Additionally, these improvements in drug discovery have focused a lot of emphasis on the invention of creative methods to deliver them effectively and efficiently. Long-acting injectable systems are one innovator of such strategies [2]. These systems can sustain therapeutic drug levels for extended periods, offering benefits such as improved bioavailability, consistent plasma concentration, and targeted drug delivery. Furthermore, they are adaptable for various routes of administration, including subcutaneous, intramuscular, and intra-articular, with drug release rates controlled by the formulation’s characteristics [3,4,5]. Both the vehicle and drug characteristics, as well as how the drug interacts with both the tissue and the vehicle, control the drug absorption kinetics and, thus, its duration of action. | |
| dc.description.abstract | Abstract: Lipid and/or polymer-based drug conjugates can potentially minimize side effects by increasing drug accumulation at target sites and thus augment patient compliance. Formulation factors can present a potent influence on the characteristics of the obtained systems. The selection of an appropriate solvent with satisfactory rheological properties, miscibility, and biocompatibility is essential to optimize drug release. This work presents a computational study of the effect of the basic formulation factors on the characteristics of the obtained in situ-forming particulates (IFPs) encapsulating a model drug using a 21 .31 full factorial experimental design. The emulsion method was employed for the preparation of lipid and/or polymer-based IFPs. The IFP release profiles and parameters were computed. Additionally, a desirability study was carried out to choose the optimum formulation for further morphological examination, rheological study, and PBPK physiological modeling. Results revealed that the type of particulate forming agent (lipid/polymer) and the incorporation of structure additives like Brij 52 and Eudragit RL can effectively augment the release profile as well as the burst of the drug. The optimized formulation exhibited a pseudoplastic rheological behavior and yielded uniformly spherical-shaped dense particulates with a PS of 573.92 ± 23.5 nm upon injection. Physiological modeling simulation revealed the pioneer pharmacokinetic properties of the optimized formulation compared to the observed data. These results assure the importance of controlling the formulation factors during drug development, the potentiality of the optimized IFPs for the intramuscular delivery of piroxicam, and the reliability of PBPK physiological modeling in predicting the biological performance of new formulations with effective cost management. Keywords: in situ forming nanoparticles; parenteral; targeted drug delivery; design of experiment; PDLG; cholesterol; PBPK; lipid; polymer | |
| dc.identifier.citation | El Hoffy, N. M., Yacoub, A. S., Ghoneim, A. M., Ibrahim, M., Ammar, H. O., & Eissa, N. (2023). Computational Amendment of Parenteral In Situ Forming Particulates’ Characteristics: Design of Experiment and PBPK Physiological Modeling. Pharmaceutics, 15(10), 2513. | |
| dc.identifier.doi | https://doi.org/10.3390/pharmaceutics15102513 | |
| dc.identifier.uri | https://dspace.adu.ac.ae/handle/1/801 | |
| dc.language.iso | en | |
| dc.publisher | MDPI | |
| dc.title | Computational Amendment of Parenteral In Situ Forming Particulates’ Characteristics: Design of Experiment and PBPK Physiological Modeling | |
| dc.type | Article |