Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation
Mucoadhesive nanosized crystalline aggregates (NCs) can be delivered by the gastrointestinal, nasal, or pulmonary route to improve retention at particular sites. Itopride hydrochloride (ITH) was selected as a drug candidate due to its absorption from the upper gastrointestinal tract. For drug locali...
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MDPI AG
2023-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/7/925 |
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| author | Moutaz Y. Badr Pratap Basim Khaled M. Hosny Waleed Y. Rizg N. Raghavendra Naveen Mallesh Kurakula Fayez Alsulaimani Awaji Y. Safhi Fahad Y. Sabei Mohammed Alissa Abdulmohsin J. Alamoudi |
| author_facet | Moutaz Y. Badr Pratap Basim Khaled M. Hosny Waleed Y. Rizg N. Raghavendra Naveen Mallesh Kurakula Fayez Alsulaimani Awaji Y. Safhi Fahad Y. Sabei Mohammed Alissa Abdulmohsin J. Alamoudi |
| author_sort | Moutaz Y. Badr |
| collection | DOAJ |
| description | Mucoadhesive nanosized crystalline aggregates (NCs) can be delivered by the gastrointestinal, nasal, or pulmonary route to improve retention at particular sites. Itopride hydrochloride (ITH) was selected as a drug candidate due to its absorption from the upper gastrointestinal tract. For drug localization and target-specific actions, mucoadhesive polymers are essential. The current work aimed to use second-generation mucoadhesive polymers (i.e., thiolated polymers) to enhance mucoadhesive characteristics. An ITH-NC formulation was enhanced using response surface methodology. Concentrations of Tween 80 and Polyvinyl pyrrolidone (PVP K-30) were selected as independent variables that could optimize the formulation to obtain the desired entrapment efficacy and particle size/diameter. It was found that a formulation prepared using Tween 80 at a concentration of 2.55% and PVP K-30 at 2% could accomplish the goals for which an optimized formulation was needed. Either xanthan gum (XG) or thiolated xanthan gum (TXG) was added to the optimized formulation to determine how they affected the mucoadhesive properties of the formulation. Studies demonstrated that there was an initial burst release of ITH from the ITH/NC/XG and ITH/NC/TXG in the early hours and then a steady release for 24 h. As anticipated, the TXG formulation had a better mucin interaction, and this was needed to ensure that the drug was distributed to tissues that produce mucus. Finally, at the measured concentrations, the ITH/NC showed minimal cytotoxicity against lung cells, indicating that it may have potential for additional in vivo research. The enhanced bioavailability and mean residence time of the designed mucoadhesive NC formulations were confirmed by pharmacokinetic studies. |
| first_indexed | 2024-03-11T00:45:04Z |
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| id | doaj.art-993c6220638a49aab9ecec0d9d03499c |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T00:45:04Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj.art-993c6220638a49aab9ecec0d9d03499c2023-11-18T20:51:53ZengMDPI AGPharmaceuticals1424-82472023-06-0116792510.3390/ph16070925Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo InvestigationMoutaz Y. Badr0Pratap Basim1Khaled M. Hosny2Waleed Y. Rizg3N. Raghavendra Naveen4Mallesh Kurakula5Fayez Alsulaimani6Awaji Y. Safhi7Fahad Y. Sabei8Mohammed Alissa9Abdulmohsin J. Alamoudi10Department of Pharmaceutics, College of Pharmacy, Umm Al-Qura University, Makkah 24381, Saudi ArabiaThermoFisher Scientific, Cincinnati, OH 45237, USADepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B.G Nagara, Karnataka 571448, IndiaCURE Pharmaceutical, Oxnard, CA 93033, USADepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi ArabiaMucoadhesive nanosized crystalline aggregates (NCs) can be delivered by the gastrointestinal, nasal, or pulmonary route to improve retention at particular sites. Itopride hydrochloride (ITH) was selected as a drug candidate due to its absorption from the upper gastrointestinal tract. For drug localization and target-specific actions, mucoadhesive polymers are essential. The current work aimed to use second-generation mucoadhesive polymers (i.e., thiolated polymers) to enhance mucoadhesive characteristics. An ITH-NC formulation was enhanced using response surface methodology. Concentrations of Tween 80 and Polyvinyl pyrrolidone (PVP K-30) were selected as independent variables that could optimize the formulation to obtain the desired entrapment efficacy and particle size/diameter. It was found that a formulation prepared using Tween 80 at a concentration of 2.55% and PVP K-30 at 2% could accomplish the goals for which an optimized formulation was needed. Either xanthan gum (XG) or thiolated xanthan gum (TXG) was added to the optimized formulation to determine how they affected the mucoadhesive properties of the formulation. Studies demonstrated that there was an initial burst release of ITH from the ITH/NC/XG and ITH/NC/TXG in the early hours and then a steady release for 24 h. As anticipated, the TXG formulation had a better mucin interaction, and this was needed to ensure that the drug was distributed to tissues that produce mucus. Finally, at the measured concentrations, the ITH/NC showed minimal cytotoxicity against lung cells, indicating that it may have potential for additional in vivo research. The enhanced bioavailability and mean residence time of the designed mucoadhesive NC formulations were confirmed by pharmacokinetic studies.https://www.mdpi.com/1424-8247/16/7/925optimizationsustainability of natural resourcesnanosizedcrystalline aggregatesmucoadhesivethiolated |
| spellingShingle | Moutaz Y. Badr Pratap Basim Khaled M. Hosny Waleed Y. Rizg N. Raghavendra Naveen Mallesh Kurakula Fayez Alsulaimani Awaji Y. Safhi Fahad Y. Sabei Mohammed Alissa Abdulmohsin J. Alamoudi Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation Pharmaceuticals optimization sustainability of natural resources nanosized crystalline aggregates mucoadhesive thiolated |
| title | Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation |
| title_full | Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation |
| title_fullStr | Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation |
| title_full_unstemmed | Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation |
| title_short | Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation |
| title_sort | design and evaluation of s protected thiolated based itopride hydrochloride polymeric nanocrystals for functional dyspepsia qbd driven optimization in situ in vitro and in vivo investigation |
| topic | optimization sustainability of natural resources nanosized crystalline aggregates mucoadhesive thiolated |
| url | https://www.mdpi.com/1424-8247/16/7/925 |
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