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Background <p>Posaconazole (POS) drug is widely used as an antifungal effective against Candida infections falls under the Biopharmaceutics Classification System (BCS) Class II. Because of its very low water solubility and hydrophobic properties, solubility is the rate limiting step which affects the absorption rate, to overcome these problems the current research concentrates on development of Solid Self Nanoemulsifying Drug Delivery System (S-SNEDDS) for the oral administration of POS to improve the solubility and hence bioavailability. Increase of bioavailability might result in potential toxicity as a large amount of drug is absorbed. The aim of this study is to evaluate the potential toxicity by using <i>albino wistar rats</i>.</p> Method <p>The choice of formulation components, Capmul MCM C8 as an oil, Tween 20 as a surfactant, and Acrysol K140 as a co-surfactant depended on their ability to solubilize POS and their capacity to form emulsions. The optimized Liquid Self Nanoemulsifying Drug Delivery System (L-SNEDDS) was then converted into a solid state by employing Neusilin® US2 as a porous carrier, improving the product's stability and handling ease. The optimized S-SNEDDS formulation was evaluated for the potential toxicity by using <i>albino wistar rats</i>. Acute, sub-acute and chronic toxicity parameters measured comparatively for S-SNEDDS with the pure drug like physical parameters, histopathology and liver function assay.</p> Results <p>In the existing study none of the rats showed observable signs of acute and sub-acute toxicity for developed formulation of POS S-SNEDDS. The various enzymes level for pure POS drug powder treated rats were observed as SGPT 48.5 U/L, SGOT 54.1 U/L, ALP 197 U/L, LDH 145.4 U/L, total bilirubin 0.181&#xa0;mg/dL and direct bilirubin 0.152&#xa0;mg/dL. While optimized POS loaded S-SNEDDS formulation treated rats were shown SGPT 47.3 U/L, SGOT 49.7 U/L, ALP 201 U/L, LDH 132 U/L, total bilirubin 0.15&#xa0;mg/dL and direct bilirubin 0.127&#xa0;mg/dL. Here minor elevation of liver enzyme levels and hepatocellular damage at little extent had been reported in pure POS drug powder treated rats than POS S-SNEDDS treated group.</p> Conclusion <p>According to the data, POS S-SNEDDS formulation had not shown any harmful effects in acute, sub-acute and chronic toxicity studies on rats. As well as it depicted normal liver function assay result which indicated POS S-SNEDDS formulation is safer in preclinical study.</p>

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Toxicity Studies of Solid Self Nanoemulsifying Drug Delivery System (S-SNEDDS) Containing Posaconazole in Wistar Rats

  • 期刊论文

  • 发表日期：

    2025年6月11日

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  • Hardikkumar K. Patel,
  • Naitikkumar D. Trivedi,
  • Vaishali T. Thakkar,
  • Alpesh D. Patel,
  • Upama N. Trivedi,
  • Devesh U. Kapoor

摘要

Background

Posaconazole (POS) drug is widely used as an antifungal effective against Candida infections falls under the Biopharmaceutics Classification System (BCS) Class II. Because of its very low water solubility and hydrophobic properties, solubility is the rate limiting step which affects the absorption rate, to overcome these problems the current research concentrates on development of Solid Self Nanoemulsifying Drug Delivery System (S-SNEDDS) for the oral administration of POS to improve the solubility and hence bioavailability. Increase of bioavailability might result in potential toxicity as a large amount of drug is absorbed. The aim of this study is to evaluate the potential toxicity by using albino wistar rats.

Method

The choice of formulation components, Capmul MCM C8 as an oil, Tween 20 as a surfactant, and Acrysol K140 as a co-surfactant depended on their ability to solubilize POS and their capacity to form emulsions. The optimized Liquid Self Nanoemulsifying Drug Delivery System (L-SNEDDS) was then converted into a solid state by employing Neusilin® US2 as a porous carrier, improving the product's stability and handling ease. The optimized S-SNEDDS formulation was evaluated for the potential toxicity by using albino wistar rats. Acute, sub-acute and chronic toxicity parameters measured comparatively for S-SNEDDS with the pure drug like physical parameters, histopathology and liver function assay.

Results

In the existing study none of the rats showed observable signs of acute and sub-acute toxicity for developed formulation of POS S-SNEDDS. The various enzymes level for pure POS drug powder treated rats were observed as SGPT 48.5 U/L, SGOT 54.1 U/L, ALP 197 U/L, LDH 145.4 U/L, total bilirubin 0.181 mg/dL and direct bilirubin 0.152 mg/dL. While optimized POS loaded S-SNEDDS formulation treated rats were shown SGPT 47.3 U/L, SGOT 49.7 U/L, ALP 201 U/L, LDH 132 U/L, total bilirubin 0.15 mg/dL and direct bilirubin 0.127 mg/dL. Here minor elevation of liver enzyme levels and hepatocellular damage at little extent had been reported in pure POS drug powder treated rats than POS S-SNEDDS treated group.

Conclusion

According to the data, POS S-SNEDDS formulation had not shown any harmful effects in acute, sub-acute and chronic toxicity studies on rats. As well as it depicted normal liver function assay result which indicated POS S-SNEDDS formulation is safer in preclinical study.