Md Ali Mujtaba, Md Abdur Rashid, Yahya Alhamhoom, Purushottam Gangane, Mohini Janardan Jagtap, Mohammad J Akbar, Sandeep Ashokrao Wathore, Mohammed Kaleem, Gamal Osman Elhassan, Mohammad Khalid
{"title":"实验设计辅助依非韦伦固体分散吸附剂的配方优化及对其溶出和流动性能的影响。","authors":"Md Ali Mujtaba, Md Abdur Rashid, Yahya Alhamhoom, Purushottam Gangane, Mohini Janardan Jagtap, Mohammad J Akbar, Sandeep Ashokrao Wathore, Mohammed Kaleem, Gamal Osman Elhassan, Mohammad Khalid","doi":"10.2147/DDDT.S517021","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Efavirenz (EFZ) is an anti-HIV drug that has been administered as first-line treatment, which exhibits low solubility and poor oral bioavailability. Therefore, the current study aimed to develop a solid dispersion adsorbate (SDA) to enhance the dissolution rate and flow properties of EFZ for solid oral dosage forms.</p><p><strong>Methods: </strong>The SDA of EFZ was prepared using the fusion method with PEG-6000 and poloxamer-188 as carriers, along with avicel PH-102 and aerosil-200 as adsorbents. 3<sup>2</sup> full factorial approach was employed to formulate the SDA and evaluate the effects of two independent factors X<sub>1</sub>: the ratio of PEG-6000 to EFZ in the solid dispersion, and X<sub>2</sub>: the ratio of aerosil-200 to the solid dispersion. The dependent factors analyzed were Y<sub>1</sub>: the time required for 85% of the drug release, and Y<sub>2</sub>: angle of repose.</p><p><strong>Results: </strong>The optimized formulation (F9) was selected through numerical optimization, demonstrating the desired drug release and excellent flow properties of the pre-compressed SDA. Fourier transform infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) of SDA showed the transformation of crystalline to amorphous form of EFZ, which is responsible for improving drug dissolution. The direct compression method was used to prepare SDA-EFZ tablets (equivalent to 25 mg EFZ) along with plain EFZ. The dissolution efficiency increased from 50.68% for plain EFZ tablets to 96.18% for EFZ-SDA tablets. Furthermore, the cumulative percentage drug release (%CDR) from SDA tablets was nearly double that of plain EFZ tablets. Stability testing indicated no significant changes in drug content and %CDR of the SDA tablets.</p><p><strong>Conclusion: </strong>The findings of this study suggest that the SDA method is an effective approach for enhancing the dissolution and flow characteristics of EFZ and may serve as an alternative strategy for preparing solid dosage forms in commercial applications.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3715-3734"},"PeriodicalIF":4.7000,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067463/pdf/","citationCount":"0","resultStr":"{\"title\":\"Design of Experiments Assisted Formulation Optimization and Evaluation of Efavirenz Solid Dispersion Adsorbate for Improvement in Dissolution and Flow Properties.\",\"authors\":\"Md Ali Mujtaba, Md Abdur Rashid, Yahya Alhamhoom, Purushottam Gangane, Mohini Janardan Jagtap, Mohammad J Akbar, Sandeep Ashokrao Wathore, Mohammed Kaleem, Gamal Osman Elhassan, Mohammad Khalid\",\"doi\":\"10.2147/DDDT.S517021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Efavirenz (EFZ) is an anti-HIV drug that has been administered as first-line treatment, which exhibits low solubility and poor oral bioavailability. Therefore, the current study aimed to develop a solid dispersion adsorbate (SDA) to enhance the dissolution rate and flow properties of EFZ for solid oral dosage forms.</p><p><strong>Methods: </strong>The SDA of EFZ was prepared using the fusion method with PEG-6000 and poloxamer-188 as carriers, along with avicel PH-102 and aerosil-200 as adsorbents. 3<sup>2</sup> full factorial approach was employed to formulate the SDA and evaluate the effects of two independent factors X<sub>1</sub>: the ratio of PEG-6000 to EFZ in the solid dispersion, and X<sub>2</sub>: the ratio of aerosil-200 to the solid dispersion. The dependent factors analyzed were Y<sub>1</sub>: the time required for 85% of the drug release, and Y<sub>2</sub>: angle of repose.</p><p><strong>Results: </strong>The optimized formulation (F9) was selected through numerical optimization, demonstrating the desired drug release and excellent flow properties of the pre-compressed SDA. Fourier transform infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) of SDA showed the transformation of crystalline to amorphous form of EFZ, which is responsible for improving drug dissolution. The direct compression method was used to prepare SDA-EFZ tablets (equivalent to 25 mg EFZ) along with plain EFZ. The dissolution efficiency increased from 50.68% for plain EFZ tablets to 96.18% for EFZ-SDA tablets. Furthermore, the cumulative percentage drug release (%CDR) from SDA tablets was nearly double that of plain EFZ tablets. Stability testing indicated no significant changes in drug content and %CDR of the SDA tablets.</p><p><strong>Conclusion: </strong>The findings of this study suggest that the SDA method is an effective approach for enhancing the dissolution and flow characteristics of EFZ and may serve as an alternative strategy for preparing solid dosage forms in commercial applications.</p>\",\"PeriodicalId\":11290,\"journal\":{\"name\":\"Drug Design, Development and Therapy\",\"volume\":\"19 \",\"pages\":\"3715-3734\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-05-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067463/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Design, Development and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/DDDT.S517021\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Design, Development and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/DDDT.S517021","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Design of Experiments Assisted Formulation Optimization and Evaluation of Efavirenz Solid Dispersion Adsorbate for Improvement in Dissolution and Flow Properties.
Background: Efavirenz (EFZ) is an anti-HIV drug that has been administered as first-line treatment, which exhibits low solubility and poor oral bioavailability. Therefore, the current study aimed to develop a solid dispersion adsorbate (SDA) to enhance the dissolution rate and flow properties of EFZ for solid oral dosage forms.
Methods: The SDA of EFZ was prepared using the fusion method with PEG-6000 and poloxamer-188 as carriers, along with avicel PH-102 and aerosil-200 as adsorbents. 32 full factorial approach was employed to formulate the SDA and evaluate the effects of two independent factors X1: the ratio of PEG-6000 to EFZ in the solid dispersion, and X2: the ratio of aerosil-200 to the solid dispersion. The dependent factors analyzed were Y1: the time required for 85% of the drug release, and Y2: angle of repose.
Results: The optimized formulation (F9) was selected through numerical optimization, demonstrating the desired drug release and excellent flow properties of the pre-compressed SDA. Fourier transform infrared (FTIR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) of SDA showed the transformation of crystalline to amorphous form of EFZ, which is responsible for improving drug dissolution. The direct compression method was used to prepare SDA-EFZ tablets (equivalent to 25 mg EFZ) along with plain EFZ. The dissolution efficiency increased from 50.68% for plain EFZ tablets to 96.18% for EFZ-SDA tablets. Furthermore, the cumulative percentage drug release (%CDR) from SDA tablets was nearly double that of plain EFZ tablets. Stability testing indicated no significant changes in drug content and %CDR of the SDA tablets.
Conclusion: The findings of this study suggest that the SDA method is an effective approach for enhancing the dissolution and flow characteristics of EFZ and may serve as an alternative strategy for preparing solid dosage forms in commercial applications.
期刊介绍：
Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications.
The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas.
Specific topics covered by the journal include:
Drug target identification and validation
Phenotypic screening and target deconvolution
Biochemical analyses of drug targets and their pathways
New methods or relevant applications in molecular/drug design and computer-aided drug discovery*
Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes)
Structural or molecular biological studies elucidating molecular recognition processes
Fragment-based drug discovery
Pharmaceutical/red biotechnology
Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products**
Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development
Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing)
Preclinical development studies
Translational animal models
Mechanisms of action and signalling pathways
Toxicology
Gene therapy, cell therapy and immunotherapy
Personalized medicine and pharmacogenomics
Clinical drug evaluation
Patient safety and sustained use of medicines.
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