Dexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation
Naseem Ullah,1 Shahzeb Khan,1 Shaimaa Ahmed,2 Thirumala Govender,2 Hani S Faidah,3 Marcel de Matas,4 Muhammad Shahid,5 Muhammad Usman Minhas,6 Muhammad Sohail,7 Muhammad Khurram8 1Department of Pharmacy, University of Malakand, Chakdara, Pakistan; 2Discipline of Pharmaceutical Sciences, School of H...
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2018
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dexibuprofen nanocrystals dissolution antinociceptive activity molecular modeling stability Medicine (General) R5-920 |
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dexibuprofen nanocrystals dissolution antinociceptive activity molecular modeling stability Medicine (General) R5-920 Ullah N Khan S Ahmed S Govender T Faidah HS de Matas M Shahid M Minhas MU Sohail M Khurram M Dexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation |
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Naseem Ullah,1 Shahzeb Khan,1 Shaimaa Ahmed,2 Thirumala Govender,2 Hani S Faidah,3 Marcel de Matas,4 Muhammad Shahid,5 Muhammad Usman Minhas,6 Muhammad Sohail,7 Muhammad Khurram8 1Department of Pharmacy, University of Malakand, Chakdara, Pakistan; 2Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; 3Department of Microbiology, Faculty of Medicine, Umm Al Qura University, Makkah, Kingdom of Saudi Arabia; 4SEDA Pharmaceutical Development Services, The BioHub at Alderley Park, Cheshire, UK; 5Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Pakistan; 6Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Punjab, Pakistan; 7Department of Pharmacy, COMSATS, Abbottabad, Pakistan; 8Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Pakistan Background: The aim of this study was to prepare and evaluate the impact of polymers on fabricating stable dexibuprofen (Dexi) nanocrystals with enhanced therapeutic potential, using a low energy, anti-solvent precipitation method coupled with molecular modelling approach. Methods: Dexi nanocrystals were prepared using antisolvent precipitation with syringe pump. Crystallinity of the processed Dexi particles was confirmed using differential scanning calorimetry and powdered X-ray diffraction and transmission electron microscopy. Dissolution of Dexi nanocrystals was compared with raw Dexi and marketed tablets. Molecular modelling study was coupled with experimental studies to rationalise the appropriate polymers for stable Dexi nanocrystals. Antinociceptive study was carried out using balb mice. Results: Combinations of hydroxypropyl methylcellulose (HPMC)–polyvinyl pyrrolidone (PVP) and HPMC–Eudragit (EUD) were shown to be very effective in producing stable Dexi nanocrystals with particle sizes of 85.0±2.5 nm and 90±3.0 nm, and polydispersity of 0.179±0.01, 0.182±0.02, respectively. The stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C–8°C and 25°C were more stable than those at 40°C. The maximum recovery of Dexi nanocrystals was observed from the formulations using the combination of HPMC–PVP and HPMC–EUD, which equated to 98% and 94% of the nominal active drug content respectively. The saturation solubility of the Dexi nanocrystals was substantially increased to 270.0±3.5 µg/mL compared to the raw Dexi in water (51.0±2.0 µg/mL) and stabilizer solution (92.0±3.0 µg/mL). Enhanced dissolution rate (P<0.05) was observed for the Dexi nanocrystals compared to the unprocessed drug substance and marketed tablets. Dexi nanocrystals produced the analgesic effect at much lower doses (5 mg/kg) than that of control standard, diclofenac sodium (20 mg/kg) and Dexi counterparts (40 mg/kg). Conclusion: HPMC-PVP and HPMC-EUD were found the best polymer combination to stabilise Dexi nanocrystals. The Dexi nanocrystals exhibited significant dissolution, solubility and analgesic effect compared to the raw Dexi and the control standard diclofenac sodium. Keywords: dexibuprofen, nanocrystals, dissolution, antinociceptive activity, molecular modeling, stability |
| format |
article |
| author |
Ullah N Khan S Ahmed S Govender T Faidah HS de Matas M Shahid M Minhas MU Sohail M Khurram M |
| author_facet |
Ullah N Khan S Ahmed S Govender T Faidah HS de Matas M Shahid M Minhas MU Sohail M Khurram M |
| author_sort |
Ullah N |
| title |
Dexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation |
| title_short |
Dexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation |
| title_full |
Dexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation |
| title_fullStr |
Dexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation |
| title_full_unstemmed |
Dexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation |
| title_sort |
dexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation |
| publisher |
Dove Medical Press |
| publishDate |
2018 |
| url |
https://doaj.org/article/d14c232dfa4841e7a88712fc7447f5a9 |
| work_keys_str_mv |
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oai:doaj.org-article:d14c232dfa4841e7a88712fc7447f5a92021-12-02T00:31:38ZDexibuprofen nanocrystals with improved therapeutic performance: fabrication, characterization, in silico modeling, and in vivo evaluation1178-2013https://doaj.org/article/d14c232dfa4841e7a88712fc7447f5a92018-03-01T00:00:00Zhttps://www.dovepress.com/dexibuprofen-nanocrystals-with-improved-therapeutic-performance-fabric-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Naseem Ullah,1 Shahzeb Khan,1 Shaimaa Ahmed,2 Thirumala Govender,2 Hani S Faidah,3 Marcel de Matas,4 Muhammad Shahid,5 Muhammad Usman Minhas,6 Muhammad Sohail,7 Muhammad Khurram8 1Department of Pharmacy, University of Malakand, Chakdara, Pakistan; 2Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; 3Department of Microbiology, Faculty of Medicine, Umm Al Qura University, Makkah, Kingdom of Saudi Arabia; 4SEDA Pharmaceutical Development Services, The BioHub at Alderley Park, Cheshire, UK; 5Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Pakistan; 6Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Punjab, Pakistan; 7Department of Pharmacy, COMSATS, Abbottabad, Pakistan; 8Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Pakistan Background: The aim of this study was to prepare and evaluate the impact of polymers on fabricating stable dexibuprofen (Dexi) nanocrystals with enhanced therapeutic potential, using a low energy, anti-solvent precipitation method coupled with molecular modelling approach. Methods: Dexi nanocrystals were prepared using antisolvent precipitation with syringe pump. Crystallinity of the processed Dexi particles was confirmed using differential scanning calorimetry and powdered X-ray diffraction and transmission electron microscopy. Dissolution of Dexi nanocrystals was compared with raw Dexi and marketed tablets. Molecular modelling study was coupled with experimental studies to rationalise the appropriate polymers for stable Dexi nanocrystals. Antinociceptive study was carried out using balb mice. Results: Combinations of hydroxypropyl methylcellulose (HPMC)–polyvinyl pyrrolidone (PVP) and HPMC–Eudragit (EUD) were shown to be very effective in producing stable Dexi nanocrystals with particle sizes of 85.0±2.5 nm and 90±3.0 nm, and polydispersity of 0.179±0.01, 0.182±0.02, respectively. The stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C–8°C and 25°C were more stable than those at 40°C. The maximum recovery of Dexi nanocrystals was observed from the formulations using the combination of HPMC–PVP and HPMC–EUD, which equated to 98% and 94% of the nominal active drug content respectively. The saturation solubility of the Dexi nanocrystals was substantially increased to 270.0±3.5 µg/mL compared to the raw Dexi in water (51.0±2.0 µg/mL) and stabilizer solution (92.0±3.0 µg/mL). Enhanced dissolution rate (P<0.05) was observed for the Dexi nanocrystals compared to the unprocessed drug substance and marketed tablets. Dexi nanocrystals produced the analgesic effect at much lower doses (5 mg/kg) than that of control standard, diclofenac sodium (20 mg/kg) and Dexi counterparts (40 mg/kg). Conclusion: HPMC-PVP and HPMC-EUD were found the best polymer combination to stabilise Dexi nanocrystals. The Dexi nanocrystals exhibited significant dissolution, solubility and analgesic effect compared to the raw Dexi and the control standard diclofenac sodium. Keywords: dexibuprofen, nanocrystals, dissolution, antinociceptive activity, molecular modeling, stabilityUllah NKhan SAhmed SGovender TFaidah HSde Matas MShahid MMinhas MUSohail MKhurram MDove Medical Pressarticledexibuprofennanocrystalsdissolutionantinociceptive activitymolecular modelingstabilityMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 1677-1692 (2018) |