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Background <p>Silodosin (SLD) has poor oral bioavailability due to poor dissolution and P-gp-mediated efflux, requiring a formulation strategy to improve release and absorption. The current work was directed at the statistical creation and optimization of sprinkle pellets (SP) with the addition of SLD and PIP as bioenhancers, using systematic design methods and detailed physicochemical characterisation to achieve better performance and stability.</p> Methods <p>A confirmed UV spectrophotometric absorbance correction system was created to estimate both SLD and PIP at the same time and showed good linearity (R<sup>2</sup> = 0.999 and 0.991, respectively), accuracy (99.7-101.8%), and precision (&lt; 2%RSD). A Plackett-Burman design (PBD) was used to screen seven critical attributes, after which optimization was performed using the Central Composite design (CCD). Impeller speed (75–150&#xa0;rpm), extruder sieve size (0.8–1.2&#xa0;mm), and time of spheronization (120–360&#xa0;s) were used as independent factors, and the responses were particle size (Y1), aspect ratio (Y2), and release of the drug after 30&#xa0;min (Y3). DSC, FTIR, SEM, in vitro dissolution, ex vivo absorption, and stability of the optimized pellets were performed.</p> Results <p>PBD found extruder sieve size to be the most significant influence on particle size (F = 2180.51), aspect ratio, spheronization time (F = 694.23), and speed of impeller to release drug (F = 96.01). The models developed using the CCD were highly predictive, with the following R2 values: 0.9888 (Y1), 0.9716 (Y2), and 0.9985 (Y3). The optimized batch had a particle size of approximately 634&#xa0;μm, an aspect ratio of 1.03 ± 0.007, friability of 0.16%, and drug release &gt; 90% in 100&#xa0;min. The drug content of the two APIs was greater than 95%. DSC reflected a lower degree of crystallinity, FTIR reflected the stability of the chemical, and SEM reflected homogeneous microporous morphology. Ex vivo experiments showed much greater absorption in the presence of PIP than in SLD alone (58.02 ± 2.12% release at 60&#xa0;min). In stability testing (more than six months), there was a low degree of difference (less than 5) between the drug content and drug release.</p> Conclusion <p>The statistically improved SP formulation exhibited excellent sphericity, mechanical strength, dissolution rate, improved absorption, and stability. SLD showed higher absorption with PIP compared to SLD alone. The combined analytical validation and design-based optimization strategy was used to ensure a strong, reproducible, and pharmaceutically acceptable pellet formulation that could enhance the oral delivery of SLD to geriatric patient.</p>

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QbD-Assisted Optimization of Geriatric-Friendly Co-Formulated Sprinkle Pellets of Silodosin and Piperine

  • 期刊论文

  • 发表日期：

    2026年5月20日

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  • Hardik Rana,
  • Jeet Sankaliya,
  • Varsha Gadhvi,
  • Vaishali Thakkar,
  • Tejal Gandhi

摘要

Background

Silodosin (SLD) has poor oral bioavailability due to poor dissolution and P-gp-mediated efflux, requiring a formulation strategy to improve release and absorption. The current work was directed at the statistical creation and optimization of sprinkle pellets (SP) with the addition of SLD and PIP as bioenhancers, using systematic design methods and detailed physicochemical characterisation to achieve better performance and stability.

Methods

A confirmed UV spectrophotometric absorbance correction system was created to estimate both SLD and PIP at the same time and showed good linearity (R2 = 0.999 and 0.991, respectively), accuracy (99.7-101.8%), and precision (< 2%RSD). A Plackett-Burman design (PBD) was used to screen seven critical attributes, after which optimization was performed using the Central Composite design (CCD). Impeller speed (75–150 rpm), extruder sieve size (0.8–1.2 mm), and time of spheronization (120–360 s) were used as independent factors, and the responses were particle size (Y1), aspect ratio (Y2), and release of the drug after 30 min (Y3). DSC, FTIR, SEM, in vitro dissolution, ex vivo absorption, and stability of the optimized pellets were performed.

Results

PBD found extruder sieve size to be the most significant influence on particle size (F = 2180.51), aspect ratio, spheronization time (F = 694.23), and speed of impeller to release drug (F = 96.01). The models developed using the CCD were highly predictive, with the following R2 values: 0.9888 (Y1), 0.9716 (Y2), and 0.9985 (Y3). The optimized batch had a particle size of approximately 634 μm, an aspect ratio of 1.03 ± 0.007, friability of 0.16%, and drug release > 90% in 100 min. The drug content of the two APIs was greater than 95%. DSC reflected a lower degree of crystallinity, FTIR reflected the stability of the chemical, and SEM reflected homogeneous microporous morphology. Ex vivo experiments showed much greater absorption in the presence of PIP than in SLD alone (58.02 ± 2.12% release at 60 min). In stability testing (more than six months), there was a low degree of difference (less than 5) between the drug content and drug release.

Conclusion

The statistically improved SP formulation exhibited excellent sphericity, mechanical strength, dissolution rate, improved absorption, and stability. SLD showed higher absorption with PIP compared to SLD alone. The combined analytical validation and design-based optimization strategy was used to ensure a strong, reproducible, and pharmaceutically acceptable pellet formulation that could enhance the oral delivery of SLD to geriatric patient.