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Combination of Phospholipid Complex and Matrix Dispersion

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Abstract

Phospholipid complexation, despite being a successful, versatile, and burgeoning strategy, stickiness of phospholipids leads to suboptimal dissolution rate of drugs. This work was undertaken to fabricate simvastatin-phospholipid complex (SIM-PLC)–loaded matrix dispersion (SIM-PLC-MD) using Soluplus® as carrier material, to augment dispersibility and dissolution of SIM-PLC without altering complexation between simvastatin (SIM) and phospholipid. SIM-PLC and SIM-PLC-MD were prepared using solvent evaporation and discontinuous solvent evaporation techniques, respectively. The successful complexation was substantiated by FTIR method. Besides, PXRD and SEM studies disclosed the absence of crystallinity of SIM in both SIM-PLC and SIM-PLC-MD. The TEM analysis monitored the self-assembly of SIM-PLC and SIM-PLC-MD into colloidal structures, which could be correlated with redispersion in GIT fluids upon oral administration. The considerable increase in hydrophilicity of SIM-PLC-MD and SIM-PLC as evident from partition coefficient experiment can further be correlated with their remarkably improved solubility profiles in the following pattern: SIM-PLC-MD˃SIM-PLC˃SIM. Correspondingly, improved dispersibility of SIM-PLC-MD in comparison to SIM-PLC can be accountable for accelerated dissolution rate by 2.53-fold and 1.5-fold in pH 1.2 and 6.8 conditions, respectively. The oral pharmacokinetic evaluation in Sprague Dawley (SD) rats revealed 3.19-fold enhancement in oral bioavailability of SIM through SIM-PLC-MD when compared with plain SIM, whereas 1.83-fold increment was observed in the case of SIM-PLC. Finally, the efficacy experimentation in SD rats revealed that SIM-PLC-MD significantly reduced triglycerides and cholesterol levels in comparison to SIM and SIM-PLC. These outcomes suggest that a matrix dispersion strategy improves oral bioavailability and hypolipidemic activity of SIM.

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Abbreviations

SIM:

simvastatin

SIM-PLC:

simvastatin-phospholipid complex

SIM-PLC-MD:

simvastatin-phospholipid complex–loaded matrix dispersion

PM:

physical mixture

FTIR:

Fourier transform infrared spectroscopy

PXRD:

powder X-ray diffractometry

SEM:

scanning electron microscopy

TEM:

transmission electron microscopy

SD rats:

Sprague Dawley rats

GIT:

gastrointestinal tract

CVDs:

cardiovascular diseases

BCS:

Biopharmaceutics Classification System

HPLC:

High-performance liquid chromatography

LOD:

limit of detection

LOQ:

limit of quantification

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Acknowledgements

The authors are thankful to Director NIPER, SAS Nagar for required infrastructure support to conduct this research. We are also thankful to Mr. Sabyasachi Roy for assistance in HPLC analysis. Shamandeep Kaur is grateful to Council of Scientific & Industrial Research (CSIR), New Delhi for providing financial assistance.

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Author notes

  1. Ravi Kumar Chakravarti and Shamandeep Kaur contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmaceutical Technology (Formulations), National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S Nagar, Punjab, 160062, India

    Ravi Kumar Chakravarti

  2. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S Nagar, Punjab, 160062, India

    Shamandeep Kaur, Sanjaya K. Samal, Mahesh C. Kashyap & Abhay T. Sangamwar

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  1. Ravi Kumar Chakravarti
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Contributions

Ravi Kumar Chakravarti: conceptualization, investigation, data curation, validation, methodology

Shamandeep Kaur: conceptualization, formal analysis, methodology, supervision, manuscript writing (original draft)

Sanjaya K. Samal: assistance in data curation

Mahesh C. Kashyap: methodology (animal experimentation)

Abhay T. Sangamwar: conceptualization, project administration, data review, methodology, formal analysis, validation, writing — review and editing

Corresponding author

Correspondence to Abhay T. Sangamwar.

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Chakravarti, R.K., Kaur, S., Samal, S.K. et al. Combination of Phospholipid Complex and Matrix Dispersion. AAPS PharmSciTech 22, 189 (2021). https://doi.org/10.1208/s12249-021-02067-x

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