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Efavirenz Dissolution Enhancement IV—Antisolvent Nanocrystallization by Sonication, Physical Stability, and Dissolution

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Abstract

Efavirenz is a fundamental drug in the HIV therapy; however, it has a low bioavailability due to low water solubility. Particle nanonization should enhance its dissolution and therefore its bioavailability. Nanocrystallization is a promising technique for preparing drug nanocrystals. A solution containing efavirenz (EFV) and methanol was added to an aqueous solution of particle stabilizers, under sonication. The adequate polymer stabilizer and its concentration and drug load were evaluated. Particle size and zeta potential of suspensions were measured. Nanosuspensions were freeze-dried and the resulting powder was characterized by some techniques, with special attention to dissolution. Particle size and zeta potential analysis showed that HMPC and PVP were the most suitable polymers. All samples prepared with these stabilizers had nanosized particles and proper zeta potential; however, sedimentation and particle growth were detected with Turbiscan™. Time-related destabilization occurred when the lowest polymer concentration of 20% was used. SEM analysis of the dried powder shows film formation for suspensions with 40% of polymer and particle aggregation in samples with less polymer. Dissolution profiles of samples were higher than EFV raw material, although the lower the polymer concentration, the higher the dissolution.

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Abbreviations

AIDS:

Acquired immunodeficiency syndrome

ATR:

Attenuated total reflectance

BCS:

Biopharmaceutics Classification System

BS:

Backscattering

EFV:

Efavirenz

HIV:

Human immunodeficiency virus

HPC:

Hydroxypropyl cellulose

HPMC:

Hydroxypropyl methylcellulose

IDR:

Intrinsic dissolution rate

IR:

Infrared

PDI:

Polydispersity index

PVP:

Polyvinylpyrrolidone

PXRD:

Powder X-ray diffraction

SEM:

Scanning electron microscopy

SLS:

Sodium lauryl sulfate

TSI:

Turbiscan stability index

ΔBS:

Backscattering variation

ζ :

Zeta potential

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Acknowledgments

The authors want to acknowledge the Laboratory of Pharmaceutical Technology (Farmanguinhos, Fiocruz), the Laboratory of X-Ray Diffraction (UFF), the Technological Characterization Sector from the Mineral Technology Center (CETEM), the Laboratory of the Chemical Engineering Department (UFRJ), the Laboratory of Polymerization Engineering (UFRJ), the Department of Natural Products (Farmanguinhos, Fiocruz), and the Platform of Analytical Methods (Farmanguinhos, Fiocruz).

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Authors and Affiliations

  1. Laboratory of Advanced Pharmaceutical Systems, Farmanguinhos, Fiocruz, Av. Comandante. Guaranys, 447 - Jacarepaguá, Rio de Janeiro, Rio de Janeiro, 22775-903, Brazil

    Gabriela Julianelly Sartori, Livia Deris Prado & Helvécio Vinícius Antunes Rocha

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  1. Gabriela Julianelly Sartori
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  2. Livia Deris Prado
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  3. Helvécio Vinícius Antunes Rocha
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Correspondence to Gabriela Julianelly Sartori.

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Sartori, G.J., Prado, L.D. & Rocha, H.V.A. Efavirenz Dissolution Enhancement IV—Antisolvent Nanocrystallization by Sonication, Physical Stability, and Dissolution. AAPS PharmSciTech 18, 3011–3020 (2017). https://doi.org/10.1208/s12249-017-0781-6

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