Indomethacin polymeric nanosuspensions prepared by microfujidization

doi:10.1016/0168-3659(90)90103-Z

Journal of Controlled Release

Volume 12, Issue 3, May 1990, Pages 223-233

https://doi.org/10.1016/0168-3659(90)90103-Z Get rights and content

Abstract

Polymeric nanosuspensions containing indomethacin were prepared by a microfluidization-solvent evaporation method. The nanosuspensions were evaluated with respect to total drug content, drug content in the polymer and aqueous phase, particle size, drug crystallization in the aqueous phase, in vitro drug release, and stability to flocculation in 0.1 N HCl and pH 7.4 phosphate buffer. Nanosuspensions with a total drug content of 35 mg indomethacin/ml nanosuspension could be prepared without drug crystallization. More than 98% of the drug were found within the polymer phase. Unwanted drug crystallization in the aqueous phase depended on the drug loading, the drug-polymer compatibility, the organic solvent, and the type and amount of surfactant used. Indomethacin was released rapidly from ethyl cellulose nanoparticles within 15 minutes. Nanoparticles intended to provide drug release over longer periods of time were obtained by using mixtures of ethyl cellulose and poly (methyl methacrylate). In pH 7.4 buffer, anionic, nonionic and macromolecular stabilizers protected the nanosuspensions against flocculation while nonionic surf octants were good stabilizers in 0.1 N HCl.

References (29)

A.B. Larson et al.
Attainment of highly uniform solid drug dispersions employing molecular scale drug entrapment in polymeric latices
J. Pharm. Sci.
(1976)
J. Kreuter
Poly (alkyl acrylate) nanoparticles
H.J. Krause et al.
Polylactic acid nanoparticles, a colloidal drug delivery system for lipophilic drugs
Int. J. Pharm.
(1985)
R. Gurny et al.
Ocular therapy with nanoparticulate systems for controlled drug delivery
J. Controlled Release
(1985)
E. Mayhew et al.
Characterization of liposomes prepared using a microemulsifier
Biochim. Biophys. Acta
(1984)
C. Washington et al.
The production of parenteral feeding emulsions by microfluidizer
Int. J. Pharm.
(1988)
R. Bodmeier et al.
Solvent selection in the preparation of poly (dl-lactide) microspheres prepared by the solvent evaporation method
Int. J. Pharm.
(1988)
R. Bodmeier et al.
Preparation and characterization of microspheres containing the anti-inflammatory agents, indomethacin, ibuprofen, and ketoprofen
J. Controlled Release
(1989)
J.W. McGinity
Aqueous Polymeric Coatings for Pharmaceutical Applications
(1989)
R. Bodmeier et al.
Evaluation of drugcontaining polymer films prepared from aqueous latexes
Pharm. Res.
(1989)

P. Couvreur et al.

Design of biodegradable polyalkylcyanoacrylate nanoparticles as a drug carrier

R. Gurny et al.

Development of biodegradable and injectable latices for controlled release of potent drugs

Drug Dev. Ind. Pharm.

(1981)

L. Illum et al.

Drug targeting using monoclonal antibody-coated nanoparticles

S. Büyükyaylaci et al.

Polymeric dispersions as a new topical drug delivery system

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Indomethacin polymeric nanosuspensions prepared by microfujidization

Abstract

J. Pharm. Sci.

Int. J. Pharm.

J. Controlled Release

Biochim. Biophys. Acta

Int. J. Pharm.

Int. J. Pharm.

J. Controlled Release

Aqueous Polymeric Coatings for Pharmaceutical Applications

Evaluation of drugcontaining polymer films prepared from aqueous latexes

Pharm. Res.

Design of biodegradable polyalkylcyanoacrylate nanoparticles as a drug carrier

Development of biodegradable and injectable latices for controlled release of potent drugs

Drug Dev. Ind. Pharm.

Drug targeting using monoclonal antibody-coated nanoparticles

Polymeric dispersions as a new topical drug delivery system