Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB)
<b>Background:</b> The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, the USFDA gave expedited approval to bedaquiline (BDQ) as a new treatment for drug-resistant TB in adults when no other viable options are avai...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/12/10/1510 |
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| author | Rao Nargis Jahan Zafar Khan Md. Sayeed Akhtar Mohd Danish Ansari Pavitra Solanki Farhan J. Ahmad Mohd Aqil Yasmin Sultana |
| author_facet | Rao Nargis Jahan Zafar Khan Md. Sayeed Akhtar Mohd Danish Ansari Pavitra Solanki Farhan J. Ahmad Mohd Aqil Yasmin Sultana |
| author_sort | Rao Nargis Jahan |
| collection | DOAJ |
| description | <b>Background:</b> The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, the USFDA gave expedited approval to bedaquiline (BDQ) as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis, but due to poor solubility, the desired therapeutic action is not achieved. <b>Objective:</b> To develop a QbD-based self-nanoemulsifying drug delivery system of bedaquiline using various oils, surfactants, and co-surfactants. <b>Methods:</b> The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach, which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant, and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and S<sub>mix</sub>. To optimize the formulation, a Box–Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. <b>Results:</b> Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88 ± 2.1 nm with a zeta potential of 21.16 mV. In vitro studies showed enhanced drug release with a high degree of stability at 25 ± 2 °C, 60 ± 5% and 40 ± 2 °C, 75 ± 5%. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells, indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. <b>Conclusion:</b> Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings. |
| first_indexed | 2024-03-10T21:29:31Z |
| format | Article |
| id | doaj.art-902c3d04910b4b3487f46cd06d3ec872 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T21:29:31Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-902c3d04910b4b3487f46cd06d3ec8722023-11-19T15:26:30ZengMDPI AGAntibiotics2079-63822023-10-011210151010.3390/antibiotics12101510Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB)Rao Nargis Jahan0Zafar Khan1Md. Sayeed Akhtar2Mohd Danish Ansari3Pavitra Solanki4Farhan J. Ahmad5Mohd Aqil6Yasmin Sultana7Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaDepartment of Clinical Pharmacy, College of Pharmacy, King Khalid University, Al-Fara, Abha 62223, Saudi ArabiaDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaDepartment of Pharmaceutics, Delhi Pharmaceutical Sciences and Research University, New Delhi 110017, IndiaDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaDepartment of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India<b>Background:</b> The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, the USFDA gave expedited approval to bedaquiline (BDQ) as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis, but due to poor solubility, the desired therapeutic action is not achieved. <b>Objective:</b> To develop a QbD-based self-nanoemulsifying drug delivery system of bedaquiline using various oils, surfactants, and co-surfactants. <b>Methods:</b> The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach, which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant, and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and S<sub>mix</sub>. To optimize the formulation, a Box–Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. <b>Results:</b> Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88 ± 2.1 nm with a zeta potential of 21.16 mV. In vitro studies showed enhanced drug release with a high degree of stability at 25 ± 2 °C, 60 ± 5% and 40 ± 2 °C, 75 ± 5%. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells, indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. <b>Conclusion:</b> Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.https://www.mdpi.com/2079-6382/12/10/1510bedaquilineoral bioavailabilitysolubilityquality by design (QbD)pseudo-ternaryself-nanoemulsifying drug delivery systems (SNEDDS) |
| spellingShingle | Rao Nargis Jahan Zafar Khan Md. Sayeed Akhtar Mohd Danish Ansari Pavitra Solanki Farhan J. Ahmad Mohd Aqil Yasmin Sultana Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB) Antibiotics bedaquiline oral bioavailability solubility quality by design (QbD) pseudo-ternary self-nanoemulsifying drug delivery systems (SNEDDS) |
| title | Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB) |
| title_full | Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB) |
| title_fullStr | Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB) |
| title_full_unstemmed | Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB) |
| title_short | Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB) |
| title_sort | development of bedaquiline loaded snedds using quality by design qbd approach to improve biopharmaceutical attributes for the management of multidrug resistant tuberculosis mdr tb |
| topic | bedaquiline oral bioavailability solubility quality by design (QbD) pseudo-ternary self-nanoemulsifying drug delivery systems (SNEDDS) |
| url | https://www.mdpi.com/2079-6382/12/10/1510 |
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