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Quality by Design Adapted Chemically Engineered Lipid Architectonics for HIV Therapeutics and Intervention: Contriving of Formulation, Appraising the In vitro Parameters and In vivo Solubilization Potential

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Abstract

The present research encompasses a quality by design approach for fabricating lipid architectonics (LA) of an antiretroviral drug (Elvitegravir: EVR) to overcome inherent challenges of EVR to curtail its bioavailability issues. Comparative development strategy employing Box–Behnken design was undertaken between high-pressure homogenization technique and melt emulsification followed by probe sonication method, wherein the later was selected for engineering the EVR-LA. Particle size, entrapment efficiency and drug loading for EVR-LA were 84.6 ± 2.3 nm, 90.7 ± 1.8% and 8.9 ± 0.7% respectively. In vitro release studies established the supremacy of EVR-LA when compared with drug suspension (EVR-DS) by having a cumulative drug release of 96.89 ± 2.5% in pH 1.2, 89.84 ± 2.4% in pH 6.8 and 86.64 ± 2.5% in pH 7.4. Gut permeation studies revealed 19-fold increment in permeation by EVR-LA attributable to intrinsic permeation enhancing and efflux protein inhibitory activity of the lipids and surfactants incorporated. The result was validated by confocal study which exhibited enhanced permeation by EVR-LA. Dissolution study, conducted in fasted state simulated intestinal fluid (FaSSIF) and fed state simulated intestinal fluid (FeSSIF) media to ascertain the effect of food, demonstrated boosted absorption from FeSSIF media. Stability study was conducted in SGF pH 1.2, FaSSIF and FeSSIF media. The lipolysis study, conducted to determine in vivo fate of EVR, revealed 27-fold increment in solubilization potential from EVR-LA (72.43 ± 2.6%). Thus, EVR-LA exhibited remarkable in vitro results by improving gut permeation and solubilization fate along with enhanced lymphatic uptake, thereby leading to prospective in vivo fate.

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Abbreviations

HIV:

human immunodeficiency virus

ART:

antiretroviral therapy

LA:

lipid architectonics

EVR:

Elvitegravir

QbD:

quality by design

HPH:

high-pressure homogenization

BBD:

Box–Behnken design

EE:

entrapment efficiency

DL:

drug loading

TEM:

transmission electron microscopy

DSC:

differential scanning colorimetry

FTIR:

Fourier transform infrared spectroscopy

DS:

drug suspension

FaSSIF:

fasted state simulated intestinal fluid

FeSSIF:

fed state simulated intestinal fluid

SGF:

simulated gastric fluid

MCT:

medium chain triglycerides

LCT:

long-chain triglycerides

T cmc :

surface excess concentration

A cmc :

occupied area per surfactant molecule

S mix :

mixture of optimized surfactant and co-surfactant

EVR-LA:

Elvitegravir lipid architectonic

EVR-DS:

Elvitegravir drug suspension

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Acknowledgements

The authors are thankful to DST-FIST for departmental support and All India Institute of Medical Science (AIIMS) New Delhi, India, for providing technical assistance for TEM analysis.

Funding

Jamia Hamdard Silver Jubilee Research Fellowship 2017 (AS/Fellow/JH-5/2018) provided financial assistance to the first author from April 2018 to March 2019 and Indian Council of Medical Research, New Delhi (HIV/Fellowship/5/6/2018-ECD-II), for providing financial assistance to the first author from April 2019 onwards.

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Authors and Affiliations

  1. Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India

    Bushra Nabi, Saleha Rehman, Sanjula Baboota & Javed Ali

  2. Division of ECD, Indian Council of Medical Research, New Delhi, India

    Sumit Aggarwal

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  1. Bushra Nabi
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  2. Saleha Rehman
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Corresponding author

Correspondence to Javed Ali.

Ethics declarations

The study was conducted according to the Institutional Animal Ethics Committee (173/CPCSEA, 28 January 2000; Approval no. 1458), Jamia Hamdard and all guidelines were adhered to.

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The authors declare that they have no conflict of interest.

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2019 AAPS PharmSci 360, USA, and IPA Convention 2019 PharmaRIA.

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Nabi, B., Rehman, S., Aggarwal, S. et al. Quality by Design Adapted Chemically Engineered Lipid Architectonics for HIV Therapeutics and Intervention: Contriving of Formulation, Appraising the In vitro Parameters and In vivo Solubilization Potential. AAPS PharmSciTech 21, 261 (2020). https://doi.org/10.1208/s12249-020-01795-w

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