Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug Delivery
Poor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low perme...
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MDPI AG
2023-03-01
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| Series: | Gels |
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| Online Access: | https://www.mdpi.com/2310-2861/9/3/213 |
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| author | Ahmed S. Alnaim Hiral Shah Anroop B. Nair Vivek Mewada Smit Patel Shery Jacob Bandar Aldhubiab Mohamed A. Morsy Rashed M. Almuqbil Pottathil Shinu Jigar Shah |
| author_facet | Ahmed S. Alnaim Hiral Shah Anroop B. Nair Vivek Mewada Smit Patel Shery Jacob Bandar Aldhubiab Mohamed A. Morsy Rashed M. Almuqbil Pottathil Shinu Jigar Shah |
| author_sort | Ahmed S. Alnaim |
| collection | DOAJ |
| description | Poor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low permeable compounds into and across the skin. This research work was to design, develop and optimize levosulpiride-loaded niosomal gel and to evaluate its prospects for transdermal delivery. The Box-Behnken design was used to optimize niosomes by analyzing the impact of three factors (cholesterol; X<sub>1</sub>, Span 40; X<sub>2</sub>, and sonication time; X<sub>3</sub>) on the responses (particle size, Y<sub>1</sub>, and entrapment efficiency, Y<sub>2</sub>). Optimized formulation (NC) was incorporated into gel and evaluated for pharmaceutical properties, drug release study, ex vivo permeation, and in vivo absorption. The design experiment data suggest that all three independent variables influence both response variables significantly (<i>p</i> < 0.01). Pharmaceutical characteristics of NC vesicles showed the absence of drug excipient interaction, nanosize (~102.2 nm), narrow distribution (~0.218), adequate zeta potential (−49.9 mV), and spherical shape, which are suitable for transdermal therapy. The levosulpiride release rates varied significantly (<i>p</i> < 0.01) between niosomal gel formulation and control. Greater flux (<i>p</i> < 0.01) was observed with levosulpiride-loaded niosomal gel than with control gel formulation. Indeed, the drug plasma profile of niosomal gel was significantly higher (<i>p</i> < 0.005), with ~3 folds higher C<sub>max</sub> and greater bioavailability (~500% higher; <i>p</i> < 0.0001) than its counterpart. Overall, these findings imply that the use of an optimized niosomal gel formulation can increase the therapeutic efficacy of levosulpiride and may represent a promising alternative to conventional therapy. |
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| issn | 2310-2861 |
| language | English |
| last_indexed | 2024-03-11T06:29:46Z |
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| spelling | doaj.art-2064718266394123a749bad877302cb22023-11-17T11:14:51ZengMDPI AGGels2310-28612023-03-019321310.3390/gels9030213Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug DeliveryAhmed S. Alnaim0Hiral Shah1Anroop B. Nair2Vivek Mewada3Smit Patel4Shery Jacob5Bandar Aldhubiab6Mohamed A. Morsy7Rashed M. Almuqbil8Pottathil Shinu9Jigar Shah10Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutics, Arihant School of Pharmacy & BRI, Adalaj, Gandhinagar 382421, IndiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad 382481, IndiaDepartment of Pharmaceutics, Arihant School of Pharmacy & BRI, Adalaj, Gandhinagar 382421, IndiaDepartment of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman 4184, United Arab EmiratesDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutics, Institute of Pharmacy, Nirma University, Ahmedabad 382481, IndiaPoor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low permeable compounds into and across the skin. This research work was to design, develop and optimize levosulpiride-loaded niosomal gel and to evaluate its prospects for transdermal delivery. The Box-Behnken design was used to optimize niosomes by analyzing the impact of three factors (cholesterol; X<sub>1</sub>, Span 40; X<sub>2</sub>, and sonication time; X<sub>3</sub>) on the responses (particle size, Y<sub>1</sub>, and entrapment efficiency, Y<sub>2</sub>). Optimized formulation (NC) was incorporated into gel and evaluated for pharmaceutical properties, drug release study, ex vivo permeation, and in vivo absorption. The design experiment data suggest that all three independent variables influence both response variables significantly (<i>p</i> < 0.01). Pharmaceutical characteristics of NC vesicles showed the absence of drug excipient interaction, nanosize (~102.2 nm), narrow distribution (~0.218), adequate zeta potential (−49.9 mV), and spherical shape, which are suitable for transdermal therapy. The levosulpiride release rates varied significantly (<i>p</i> < 0.01) between niosomal gel formulation and control. Greater flux (<i>p</i> < 0.01) was observed with levosulpiride-loaded niosomal gel than with control gel formulation. Indeed, the drug plasma profile of niosomal gel was significantly higher (<i>p</i> < 0.005), with ~3 folds higher C<sub>max</sub> and greater bioavailability (~500% higher; <i>p</i> < 0.0001) than its counterpart. Overall, these findings imply that the use of an optimized niosomal gel formulation can increase the therapeutic efficacy of levosulpiride and may represent a promising alternative to conventional therapy.https://www.mdpi.com/2310-2861/9/3/213levosulpirideniosomesBox-Behnken designevaluationtransdermalpharmacokinetics |
| spellingShingle | Ahmed S. Alnaim Hiral Shah Anroop B. Nair Vivek Mewada Smit Patel Shery Jacob Bandar Aldhubiab Mohamed A. Morsy Rashed M. Almuqbil Pottathil Shinu Jigar Shah Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug Delivery Gels levosulpiride niosomes Box-Behnken design evaluation transdermal pharmacokinetics |
| title | Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug Delivery |
| title_full | Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug Delivery |
| title_fullStr | Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug Delivery |
| title_full_unstemmed | Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug Delivery |
| title_short | Qbd-Based Approach to Optimize Niosomal Gel of Levosulpiride for Transdermal Drug Delivery |
| title_sort | qbd based approach to optimize niosomal gel of levosulpiride for transdermal drug delivery |
| topic | levosulpiride niosomes Box-Behnken design evaluation transdermal pharmacokinetics |
| url | https://www.mdpi.com/2310-2861/9/3/213 |
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