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Bioavailability Enhancement of Poorly Water-Soluble Drugs via Nanocomposites: Formulation⁻Processing Aspects and Challenges.

作者信息

Bhakay Anagha, Rahman Mahbubur, Dave Rajesh N, Bilgili Ecevit

机构信息

Otto H. York Department of Chemical and Materials Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA.

出版信息

Pharmaceutics. 2018 Jul 8;10(3):86. doi: 10.3390/pharmaceutics10030086.


DOI:10.3390/pharmaceutics10030086
PMID:29986543
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6160929/
Abstract

Drug nanoparticles embedded in a dispersant matrix as a secondary phase, i.e., drug-laden nanocomposites, offer a versatile delivery platform for enhancing the dissolution rate and bioavailability of poorly water-soluble drugs. Drug nanoparticles are prepared by top-down, bottom-up, or combinative approaches in the form of nanosuspensions, which are subsequently dried to prepare drug-laden nanocomposites. In this comprehensive review paper, the term “nanocomposites” is used in a broad context to cover drug nanoparticle-laden intermediate products in the form of powders, cakes, and extrudates, which can be incorporated into final oral solid dosages via standard pharmaceutical unit operations, as well as drug nanoparticle-laden strip films. The objective of this paper is to review studies from 2012⁻2017 in the field of drug-laden nanocomposites. After a brief overview of the various approaches used for preparing drug nanoparticles, the review covers drying processes and dispersant formulations used for the production of drug-laden nanocomposites, as well as various characterization methods including quiescent and agitated redispersion tests. Traditional dispersants such as soluble polymers, surfactants, other water-soluble dispersants, and water-insoluble dispersants, as well as novel dispersants such as wet-milled superdisintegrants, are covered. They exhibit various functionalities such as drug nanoparticle stabilization, mitigation of aggregation, formation of nanocomposite matrix⁻film, wettability enhancement, and matrix erosion/disintegration. Major challenges such as nanoparticle aggregation and poor redispersibility that cause inferior dissolution performance of the drug-laden nanocomposites are highlighted. Literature data are analyzed in terms of usage frequency of various drying processes and dispersant classes. We provide some engineering considerations in comparing drying processes, which could account for some of the diverging trends in academia vs. industrial practice. Overall, this review provides rationale and guidance for drying process selection and robust nanocomposite formulation development, with insights into the roles of various classes of dispersants.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/dd07f4155b72/pharmaceutics-10-00086-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/de826d5c45f0/pharmaceutics-10-00086-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/b981ab0ba5e7/pharmaceutics-10-00086-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/9627294b9e59/pharmaceutics-10-00086-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/cf1515d4220f/pharmaceutics-10-00086-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/c8ac19d2ca96/pharmaceutics-10-00086-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/07719d92147d/pharmaceutics-10-00086-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/57babb772599/pharmaceutics-10-00086-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/021f971d9a15/pharmaceutics-10-00086-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/bbcc59fb2723/pharmaceutics-10-00086-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/ec82cd9697f3/pharmaceutics-10-00086-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/dd07f4155b72/pharmaceutics-10-00086-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/de826d5c45f0/pharmaceutics-10-00086-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/b981ab0ba5e7/pharmaceutics-10-00086-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/9627294b9e59/pharmaceutics-10-00086-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/cf1515d4220f/pharmaceutics-10-00086-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/c8ac19d2ca96/pharmaceutics-10-00086-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/07719d92147d/pharmaceutics-10-00086-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/57babb772599/pharmaceutics-10-00086-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/021f971d9a15/pharmaceutics-10-00086-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/bbcc59fb2723/pharmaceutics-10-00086-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/ec82cd9697f3/pharmaceutics-10-00086-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c527/6160929/dd07f4155b72/pharmaceutics-10-00086-g011.jpg

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[1]
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本文引用的文献

[1]
Multi-faceted Characterization of Wet-milled Griseofulvin Nanosuspensions for Elucidation of Aggregation State and Stabilization Mechanisms.

AAPS PharmSciTech. 2018-3-30

[2]
Pharmaceutical nanocrystals: production by wet milling and applications.

Drug Discov Today. 2018-1-8

[3]
Drug nanocrystals - Versatile option for formulation of poorly soluble materials.

Int J Pharm. 2017-12-17

[4]
Recent strategies in spray drying for the enhanced bioavailability of poorly water-soluble drugs.

J Control Release. 2017-11-5

[5]
Aceclofenac nanocrystals with enhanced in vitro, in vivo performance: formulation optimization, characterization, analgesic and acute toxicity studies.

Drug Des Devel Ther. 2017-8-23

[6]
Comparative study on stabilizing ability of food protein, non-ionic surfactant and anionic surfactant on BCS type II drug carvedilol loaded nanosuspension: Physicochemical and pharmacokinetic investigation.

Eur J Pharm Sci. 2017-8-12

[7]
Quiescent and Agitated Redispersion as a Tool for Evaluating Dispersant Effectiveness in Dissolution Enhancement of Drug-Laden Nanocomposites.

AAPS PharmSciTech. 2017-8-2

[8]
A comparative assessment of nanocomposites vs. amorphous solid dispersions prepared via nanoextrusion for drug dissolution enhancement.

Eur J Pharm Biopharm. 2017-6-3

[9]
10-Hydroxycamptothecin (HCPT) nanosuspensions stabilized by mPEG-HCPT conjugate: high stabilizing efficiency and improved antitumor efficacy.

Int J Nanomedicine. 2017-5-12

[10]
Efavirenz Dissolution Enhancement IV-Antisolvent Nanocrystallization by Sonication, Physical Stability, and Dissolution.

AAPS PharmSciTech. 2017-11

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