Study of Formulation and Process Variables for Optimization of Piroxicam Nanosuspension Using 3<sup>2</sup> Factorial Design to Improve Solubility and In Vitro Bioavailability
Piroxicam is a Biopharmaceutical Classification System (BCS) Class II drug having poor aqueous solubility and a short half-life. The rationale behind the present research was to develop a Piroxicam nanosuspension to enhance the solubility and thereby the in vitro bioavailability of the drug. Piroxic...
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MDPI AG
2023-01-01
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author | Yahya Alhamhoom Sandip M. Honmane Umme Hani Riyaz Ali M. Osmani Geetha Kandasamy Rajalakshimi Vasudevan Sharanya Paramshetti Ravindra R. Dudhal Namrata K. Kengar Manoj S. Charde |
author_facet | Yahya Alhamhoom Sandip M. Honmane Umme Hani Riyaz Ali M. Osmani Geetha Kandasamy Rajalakshimi Vasudevan Sharanya Paramshetti Ravindra R. Dudhal Namrata K. Kengar Manoj S. Charde |
author_sort | Yahya Alhamhoom |
collection | DOAJ |
description | Piroxicam is a Biopharmaceutical Classification System (BCS) Class II drug having poor aqueous solubility and a short half-life. The rationale behind the present research was to develop a Piroxicam nanosuspension to enhance the solubility and thereby the in vitro bioavailability of the drug. Piroxicam nanosuspension (PRX NS) was prepared by an anti-solvent precipitation technique and optimized using a full-factorial design. Herein, the nanosuspension was prepared using polymer polyvinylpyrrolidone (PVP) K30<sup>®</sup> and Poloxamer 188<sup>®</sup> as a stabilizer to improve the solubility and in vitro bioavailability of the drug. Nine formulations were prepared based on 3<sup>2</sup> full-factorial experimental designs to study the effect of the formulation variables such as concentration of poloxamer 188 (%) (X<sub>1</sub>) and stirring speed (rpm) (X<sub>2</sub>) as a process variable on the response of particle size (nm) and solubility (µg/mL). The prepared NS was characterized by phase solubility, Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), transmission electron microscopy (TEM), particle size, zeta potential, entrapment efficiency, and percent drug release. DSC and XRPD analysis of freeze-dried NS formulation showed conversion of PRX into a less crystalline form. NS formulations showed a reduction in the size from 443 nm to 228 nm with −22.5 to −30.5 mV zeta potential and % drug entrapment of 89.76 ± 0.76. TEM analysis confirmed the size reduction at the nano level. The solubility was increased from 44 μg/mL to 87 μg/mL by altering the independent variables. The solubility of PRX NS in water was augmented by 14- to 15-fold (87.28 μg/mL) than pure PRX (6.6 μg/mL). The optimized formulation (NS9) at drug-to-stabilizer concentration exhibited a greater drug release of approximately 96.07% after 120 min as compared to the other NS formulations and pure PRX (36.78%). Thus, all these results revealed that the prepared NS formulations have improved the solubility and in vitro dissolution compared to the pure drug. Furthermore, an increase in the drug release was observed from the NS than that of the pure PRX. All these outcomes signified that the prepared PRX NS showed an increase in solubility and in vitro dissolution behavior; which subsequently would aid in attainment of enhanced bioavailability. |
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spelling | doaj.art-71ec3c356d47486e94bd97a74b35455f2023-11-16T17:46:10ZengMDPI AGPolymers2073-43602023-01-0115348310.3390/polym15030483Study of Formulation and Process Variables for Optimization of Piroxicam Nanosuspension Using 3<sup>2</sup> Factorial Design to Improve Solubility and In Vitro BioavailabilityYahya Alhamhoom0Sandip M. Honmane1Umme Hani2Riyaz Ali M. Osmani3Geetha Kandasamy4Rajalakshimi Vasudevan5Sharanya Paramshetti6Ravindra R. Dudhal7Namrata K. Kengar8Manoj S. Charde9Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi ArabiaDepartment of Pharmaceutics, Annasaheb Dange College of B. Pharmacy, Ashta, Shivaji University, Kolhapur 416301, Maharashtra, IndiaDepartment of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi ArabiaDepartment of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSS AHER), Mysuru 570015, Karnataka, IndiaDepartment of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha 62529, Saudi ArabiaDepartment of Pharmacology, College of Pharmacy, King Khalid University, Abha 62529, Saudi ArabiaDepartment of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSS AHER), Mysuru 570015, Karnataka, IndiaDepartment of Pharmaceutics, Annasaheb Dange College of B. Pharmacy, Ashta, Shivaji University, Kolhapur 416301, Maharashtra, IndiaDepartment of Pharmaceutics, Annasaheb Dange College of B. Pharmacy, Ashta, Shivaji University, Kolhapur 416301, Maharashtra, IndiaDepartment of Pharmaceutical Chemistry, Government College of Pharmacy, Karad, Shivaji University, Kolhapur 415124, Maharashtra, IndiaPiroxicam is a Biopharmaceutical Classification System (BCS) Class II drug having poor aqueous solubility and a short half-life. The rationale behind the present research was to develop a Piroxicam nanosuspension to enhance the solubility and thereby the in vitro bioavailability of the drug. Piroxicam nanosuspension (PRX NS) was prepared by an anti-solvent precipitation technique and optimized using a full-factorial design. Herein, the nanosuspension was prepared using polymer polyvinylpyrrolidone (PVP) K30<sup>®</sup> and Poloxamer 188<sup>®</sup> as a stabilizer to improve the solubility and in vitro bioavailability of the drug. Nine formulations were prepared based on 3<sup>2</sup> full-factorial experimental designs to study the effect of the formulation variables such as concentration of poloxamer 188 (%) (X<sub>1</sub>) and stirring speed (rpm) (X<sub>2</sub>) as a process variable on the response of particle size (nm) and solubility (µg/mL). The prepared NS was characterized by phase solubility, Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), transmission electron microscopy (TEM), particle size, zeta potential, entrapment efficiency, and percent drug release. DSC and XRPD analysis of freeze-dried NS formulation showed conversion of PRX into a less crystalline form. NS formulations showed a reduction in the size from 443 nm to 228 nm with −22.5 to −30.5 mV zeta potential and % drug entrapment of 89.76 ± 0.76. TEM analysis confirmed the size reduction at the nano level. The solubility was increased from 44 μg/mL to 87 μg/mL by altering the independent variables. The solubility of PRX NS in water was augmented by 14- to 15-fold (87.28 μg/mL) than pure PRX (6.6 μg/mL). The optimized formulation (NS9) at drug-to-stabilizer concentration exhibited a greater drug release of approximately 96.07% after 120 min as compared to the other NS formulations and pure PRX (36.78%). Thus, all these results revealed that the prepared NS formulations have improved the solubility and in vitro dissolution compared to the pure drug. Furthermore, an increase in the drug release was observed from the NS than that of the pure PRX. All these outcomes signified that the prepared PRX NS showed an increase in solubility and in vitro dissolution behavior; which subsequently would aid in attainment of enhanced bioavailability.https://www.mdpi.com/2073-4360/15/3/483polymersnanosuspensionsolubilitybioavailabilityanti-solvent precipitationin vitro drug dissolution |
spellingShingle | Yahya Alhamhoom Sandip M. Honmane Umme Hani Riyaz Ali M. Osmani Geetha Kandasamy Rajalakshimi Vasudevan Sharanya Paramshetti Ravindra R. Dudhal Namrata K. Kengar Manoj S. Charde Study of Formulation and Process Variables for Optimization of Piroxicam Nanosuspension Using 3<sup>2</sup> Factorial Design to Improve Solubility and In Vitro Bioavailability Polymers polymers nanosuspension solubility bioavailability anti-solvent precipitation in vitro drug dissolution |
title | Study of Formulation and Process Variables for Optimization of Piroxicam Nanosuspension Using 3<sup>2</sup> Factorial Design to Improve Solubility and In Vitro Bioavailability |
title_full | Study of Formulation and Process Variables for Optimization of Piroxicam Nanosuspension Using 3<sup>2</sup> Factorial Design to Improve Solubility and In Vitro Bioavailability |
title_fullStr | Study of Formulation and Process Variables for Optimization of Piroxicam Nanosuspension Using 3<sup>2</sup> Factorial Design to Improve Solubility and In Vitro Bioavailability |
title_full_unstemmed | Study of Formulation and Process Variables for Optimization of Piroxicam Nanosuspension Using 3<sup>2</sup> Factorial Design to Improve Solubility and In Vitro Bioavailability |
title_short | Study of Formulation and Process Variables for Optimization of Piroxicam Nanosuspension Using 3<sup>2</sup> Factorial Design to Improve Solubility and In Vitro Bioavailability |
title_sort | study of formulation and process variables for optimization of piroxicam nanosuspension using 3 sup 2 sup factorial design to improve solubility and in vitro bioavailability |
topic | polymers nanosuspension solubility bioavailability anti-solvent precipitation in vitro drug dissolution |
url | https://www.mdpi.com/2073-4360/15/3/483 |
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