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Bioavailability Enhancement of Poorly Aqueous Soluble Atorvastatin Calcium by Solid Dispersion Technique Using a Modified Natural Polymer as a Hydrophilic Carrier

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Abstract

Purpose

The goal of this study was to improve the solubility and bioavailability of poorly water-soluble atorvastatin calcium (ATC) by solid dispersion technique using natural polymer as a hydrophilic carrier. ATC is an anti-hyperlipidemic agent with low bioavailability due to its inability to dissolve in water. As a result, an effort has been undertaken to improve ATC’s oral bioavailability by making it more water-soluble using the solid dispersion approach.

Methods

Solid dispersions (SD) were prepared by using modified Samanea saman seed gum (MSSSG) as a natural hydrophilic carrier. Amongst various available methods, solvent evaporation method was selected to prepare solid dispersions. The chemical interaction between ATC and modified hydrophilic carrier was evaluated by FTIR spectroscopy.

Results

The result of the solubility study of ATC from solid dispersion found greater solubility of ATC compared to pure drug. The outcomes of an in vitro drug release study show higher cumulative drug release at 120 min, that is 96.95% of ATC from prepared solid dispersions in comparison to pure ATC, which was only 65.36%. The prepared solid dispersions were evaluated by DSC, XRD, and SEM studies. DSC and XRD study findings revealed that the crystalline drug was converted into an amorphous state. Pharmacokinetic study in rats showed approximately 1.68- and 2.3-fold increments in Cmax and AUC respectively in case of solid dispersion as compared to plain ATC.

Conclusion

In conclusion, MSSSG could be a promising carrier to improve the solubility, dissolution rate, and bioavailability of poorly water-soluble ATC.

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Abbreviations

ATC:

Atorvastatin calcium

SD:

Solid dispersions

MSSSG:

Modified Samanea saman seed gum

NCE:

New chemical entities

API:

Active pharmaceutical ingredient

GI:

Gastrointestinal

BCS:

Bio-pharmaceutical classification system

FTIR:

Fourier transform infrared spectroscopy

DSC:

Differential scanning calorimetry

XRD:

X-ray diffraction

SEM:

Scanning electron microscopy

PM:

Physical mixture

UV:

Ultra violet

HPLC:

High-pressure liquid chromatography

Cmax :

Maximum plasma concentration

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Acknowledgements

The authors are really thankful to Zydus Cadila Healthcare Private Limited, Ahmadabad, India, for providing a gift sample of atorvastatin calcium. The authors are also grateful to Marathwada Mitra Mandal’s College of Pharmacy, Pune, for providing facilities and continuous guidance throughout the research.

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Authors and Affiliations

  1. Department of Pharmaceutics, Marathwada Mitra Mandal’s College of Pharmacy, Thergaon (Kalewadi), Pune, 411033, Maharashtra, India

    Avinash R. Tekade, Sneha U. Mathapati, Mukesh P. Ratnaparkhi & Gajanan M. Kulkarni

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  1. Avinash R. Tekade
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  2. Sneha U. Mathapati
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  3. Mukesh P. Ratnaparkhi
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Contributions

ART and SUM conceptualized and designed the research. Data acquisition was carried out by SUM and GMK. Experimental work was performed by the SUM and GMK. The animal study was carried out by ART, SUM, and GMK. All authors have contributed to the data interpretation. SUM and MPR were involved in the analysis of data by using statistics. The final draft manuscript was prepared by ART and MPR. All authors were equally involved in the critical revision of the manuscript.

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Correspondence to Avinash R. Tekade.

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The animal study protocol was approved by the IAEC (IAEC Protocol Number MMCOP/IAEC/07/2021 Dated December 30, 2021).

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Tekade, A.R., Mathapati, S.U., Ratnaparkhi, M.P. et al. Bioavailability Enhancement of Poorly Aqueous Soluble Atorvastatin Calcium by Solid Dispersion Technique Using a Modified Natural Polymer as a Hydrophilic Carrier. J Pharm Innov 18, 2182–2195 (2023). https://doi.org/10.1007/s12247-023-09783-w

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