Enhancing Pharmacokinetics and Pharmacodynamics of Rosuvastatin Calcium through the Development and Optimization of Fast-Dissolving Films
Rosuvastatin (RSV) is a widely used cholesterol-lowering medication, but its limited bioavailability due to its susceptibility to stomach pH and extensive first-pass metabolism poses a significant challenge. A fast-dissolving film (FDF) formulation of RSV was developed, characterized, and compared t...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/11/2640 |
| _version_ | 1797458035269959680 |
|---|---|
| author | Ibrahim Ashraf Pierre A. Hanna Shadeed Gad Fathy I. Abd-Allah Khalid M. El-Say |
| author_facet | Ibrahim Ashraf Pierre A. Hanna Shadeed Gad Fathy I. Abd-Allah Khalid M. El-Say |
| author_sort | Ibrahim Ashraf |
| collection | DOAJ |
| description | Rosuvastatin (RSV) is a widely used cholesterol-lowering medication, but its limited bioavailability due to its susceptibility to stomach pH and extensive first-pass metabolism poses a significant challenge. A fast-dissolving film (FDF) formulation of RSV was developed, characterized, and compared to the conventional marketed tablet to address this issue. The formulation process involved optimizing the thickness, disintegration time, and folding durability. All formulations were assessed for in vitro disintegration, thickness, folding endurance, in vitro dissolution, weight, and content uniformity. The study’s results revealed that the optimized RSV-FDF displayed a significantly faster time to maximum plasma concentration (t<sub>max</sub>) of 2 h, compared to 4 h for the marketed tablet. The maximum plasma concentration (C<sub>max</sub>) for the RSV-FDF (1.540 µg/mL ± 0.044) was notably higher than that of the marketed tablet (0.940 µg/mL ± 0.017). Additionally, the pharmacodynamic assessment in male Wistar rats demonstrated that the optimized RSV-FDF exhibited an improved lipid profile, including reduced levels of low-density lipoproteins (LDLs), elevated high-density lipoproteins (HDLs), decreased triglycerides (TGs), and lower very-low-density lipoproteins (VLDLs) compared to the conventional tablet. These findings underscore the potential of RSV-FDFs as a promising alternative to enhance the bioavailability and therapeutic efficacy of rosuvastatin in treating dyslipidemia. The faster onset of action and improved lipid-lowering effects make RSV-FDFs an attractive option for patients requiring efficient cholesterol management. |
| first_indexed | 2024-03-09T16:31:18Z |
| format | Article |
| id | doaj.art-4b5be52034934b2499cc18085d08c30c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T16:31:18Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-4b5be52034934b2499cc18085d08c30c2023-11-24T15:01:13ZengMDPI AGPharmaceutics1999-49232023-11-011511264010.3390/pharmaceutics15112640Enhancing Pharmacokinetics and Pharmacodynamics of Rosuvastatin Calcium through the Development and Optimization of Fast-Dissolving FilmsIbrahim Ashraf0Pierre A. Hanna1Shadeed Gad2Fathy I. Abd-Allah3Khalid M. El-Say4Department of Pharmaceutics, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo 11651, EgyptDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaRosuvastatin (RSV) is a widely used cholesterol-lowering medication, but its limited bioavailability due to its susceptibility to stomach pH and extensive first-pass metabolism poses a significant challenge. A fast-dissolving film (FDF) formulation of RSV was developed, characterized, and compared to the conventional marketed tablet to address this issue. The formulation process involved optimizing the thickness, disintegration time, and folding durability. All formulations were assessed for in vitro disintegration, thickness, folding endurance, in vitro dissolution, weight, and content uniformity. The study’s results revealed that the optimized RSV-FDF displayed a significantly faster time to maximum plasma concentration (t<sub>max</sub>) of 2 h, compared to 4 h for the marketed tablet. The maximum plasma concentration (C<sub>max</sub>) for the RSV-FDF (1.540 µg/mL ± 0.044) was notably higher than that of the marketed tablet (0.940 µg/mL ± 0.017). Additionally, the pharmacodynamic assessment in male Wistar rats demonstrated that the optimized RSV-FDF exhibited an improved lipid profile, including reduced levels of low-density lipoproteins (LDLs), elevated high-density lipoproteins (HDLs), decreased triglycerides (TGs), and lower very-low-density lipoproteins (VLDLs) compared to the conventional tablet. These findings underscore the potential of RSV-FDFs as a promising alternative to enhance the bioavailability and therapeutic efficacy of rosuvastatin in treating dyslipidemia. The faster onset of action and improved lipid-lowering effects make RSV-FDFs an attractive option for patients requiring efficient cholesterol management.https://www.mdpi.com/1999-4923/15/11/2640fast-dissolving filmrosuvastatinpharmacokineticshyperlipidemiadesign of experiment approach |
| spellingShingle | Ibrahim Ashraf Pierre A. Hanna Shadeed Gad Fathy I. Abd-Allah Khalid M. El-Say Enhancing Pharmacokinetics and Pharmacodynamics of Rosuvastatin Calcium through the Development and Optimization of Fast-Dissolving Films Pharmaceutics fast-dissolving film rosuvastatin pharmacokinetics hyperlipidemia design of experiment approach |
| title | Enhancing Pharmacokinetics and Pharmacodynamics of Rosuvastatin Calcium through the Development and Optimization of Fast-Dissolving Films |
| title_full | Enhancing Pharmacokinetics and Pharmacodynamics of Rosuvastatin Calcium through the Development and Optimization of Fast-Dissolving Films |
| title_fullStr | Enhancing Pharmacokinetics and Pharmacodynamics of Rosuvastatin Calcium through the Development and Optimization of Fast-Dissolving Films |
| title_full_unstemmed | Enhancing Pharmacokinetics and Pharmacodynamics of Rosuvastatin Calcium through the Development and Optimization of Fast-Dissolving Films |
| title_short | Enhancing Pharmacokinetics and Pharmacodynamics of Rosuvastatin Calcium through the Development and Optimization of Fast-Dissolving Films |
| title_sort | enhancing pharmacokinetics and pharmacodynamics of rosuvastatin calcium through the development and optimization of fast dissolving films |
| topic | fast-dissolving film rosuvastatin pharmacokinetics hyperlipidemia design of experiment approach |
| url | https://www.mdpi.com/1999-4923/15/11/2640 |
| work_keys_str_mv | AT ibrahimashraf enhancingpharmacokineticsandpharmacodynamicsofrosuvastatincalciumthroughthedevelopmentandoptimizationoffastdissolvingfilms AT pierreahanna enhancingpharmacokineticsandpharmacodynamicsofrosuvastatincalciumthroughthedevelopmentandoptimizationoffastdissolvingfilms AT shadeedgad enhancingpharmacokineticsandpharmacodynamicsofrosuvastatincalciumthroughthedevelopmentandoptimizationoffastdissolvingfilms AT fathyiabdallah enhancingpharmacokineticsandpharmacodynamicsofrosuvastatincalciumthroughthedevelopmentandoptimizationoffastdissolvingfilms AT khalidmelsay enhancingpharmacokineticsandpharmacodynamicsofrosuvastatincalciumthroughthedevelopmentandoptimizationoffastdissolvingfilms |