Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles

Jayanth Panyam, Deborah William, Alekha K. Dash, Diandra Leslie-Pelecky, Vinod Labhasetwar

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

Biodegradable nanoparticles formulated from poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA) polymers are being extensively investigated for various drug delivery applications. In this study, we hypothesize that the solid-state solubility of hydrophobic drugs in polymers could influence their encapsulation and release from nanoparticles. Dexamethasone and flutamide were used as model hydrophobic drugs. A simple, semiquantitative method based on drug-polymer phase separation was developed to determine the solid-state drug-polymer solubility. Nanoparticles using PLGA/PLA polymers were formulated using an emulsion-solvent evaporation technique, and were characterized for size, drug loading, and in vitro release. X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were used to determine the physical state of the encapsulated drug. Results demonstrated that the solid-state drug-polymer solubility depends on the polymer composition, molecular weight, and end-functional groups (ester or carboxyl) in polymer chains. Higher solid-state drug-polymer solubility resulted in higher drug encapsulation in nanoparticles, but followed an inverse correlation with the percent cumulative drug released. The XRD and DSC analyses demonstrated that the drug encapsulated in nanoparticles was present in the form of a molecular dispersion (dissolved state) in the polymer, whereas in microparticles, the drug was present in both molecular dispersion and crystalline forms. In conclusion, the solid-state drug-polymer solubility affects the nanoparticle characteristics, and thus could be used as an important preformulation parameter.

Original languageEnglish
Pages (from-to)1804-1814
Number of pages11
JournalJournal of Pharmaceutical Sciences
Volume93
Issue number7
DOIs
StatePublished - Jul 2004

Fingerprint

Encapsulation
Nanoparticles
Solubility
Polymers
Pharmaceutical Preparations
Powder Diffraction
Differential Scanning Calorimetry
polylactic acid-polyglycolic acid copolymer
poly(lactide)
Drug Liberation
X ray powder diffraction
X-Ray Diffraction
Differential scanning calorimetry
Flutamide
Emulsions
Drug delivery
Phase separation
Functional groups
Dexamethasone
Esters

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science

Cite this

Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles. / Panyam, Jayanth; William, Deborah; Dash, Alekha K.; Leslie-Pelecky, Diandra; Labhasetwar, Vinod.

In: Journal of Pharmaceutical Sciences, Vol. 93, No. 7, 07.2004, p. 1804-1814.

Research output: Contribution to journalArticle

Panyam, Jayanth ; William, Deborah ; Dash, Alekha K. ; Leslie-Pelecky, Diandra ; Labhasetwar, Vinod. / Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles. In: Journal of Pharmaceutical Sciences. 2004 ; Vol. 93, No. 7. pp. 1804-1814.
@article{344419b976ec4198a2a51cd9a9cab29b,
title = "Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles",
abstract = "Biodegradable nanoparticles formulated from poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA) polymers are being extensively investigated for various drug delivery applications. In this study, we hypothesize that the solid-state solubility of hydrophobic drugs in polymers could influence their encapsulation and release from nanoparticles. Dexamethasone and flutamide were used as model hydrophobic drugs. A simple, semiquantitative method based on drug-polymer phase separation was developed to determine the solid-state drug-polymer solubility. Nanoparticles using PLGA/PLA polymers were formulated using an emulsion-solvent evaporation technique, and were characterized for size, drug loading, and in vitro release. X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were used to determine the physical state of the encapsulated drug. Results demonstrated that the solid-state drug-polymer solubility depends on the polymer composition, molecular weight, and end-functional groups (ester or carboxyl) in polymer chains. Higher solid-state drug-polymer solubility resulted in higher drug encapsulation in nanoparticles, but followed an inverse correlation with the percent cumulative drug released. The XRD and DSC analyses demonstrated that the drug encapsulated in nanoparticles was present in the form of a molecular dispersion (dissolved state) in the polymer, whereas in microparticles, the drug was present in both molecular dispersion and crystalline forms. In conclusion, the solid-state drug-polymer solubility affects the nanoparticle characteristics, and thus could be used as an important preformulation parameter.",
author = "Jayanth Panyam and Deborah William and Dash, {Alekha K.} and Diandra Leslie-Pelecky and Vinod Labhasetwar",
year = "2004",
month = "7",
doi = "10.1002/jps.20094",
language = "English",
volume = "93",
pages = "1804--1814",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley and Sons Inc.",
number = "7",

}

TY - JOUR

T1 - Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticles

AU - Panyam, Jayanth

AU - William, Deborah

AU - Dash, Alekha K.

AU - Leslie-Pelecky, Diandra

AU - Labhasetwar, Vinod

PY - 2004/7

Y1 - 2004/7

N2 - Biodegradable nanoparticles formulated from poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA) polymers are being extensively investigated for various drug delivery applications. In this study, we hypothesize that the solid-state solubility of hydrophobic drugs in polymers could influence their encapsulation and release from nanoparticles. Dexamethasone and flutamide were used as model hydrophobic drugs. A simple, semiquantitative method based on drug-polymer phase separation was developed to determine the solid-state drug-polymer solubility. Nanoparticles using PLGA/PLA polymers were formulated using an emulsion-solvent evaporation technique, and were characterized for size, drug loading, and in vitro release. X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were used to determine the physical state of the encapsulated drug. Results demonstrated that the solid-state drug-polymer solubility depends on the polymer composition, molecular weight, and end-functional groups (ester or carboxyl) in polymer chains. Higher solid-state drug-polymer solubility resulted in higher drug encapsulation in nanoparticles, but followed an inverse correlation with the percent cumulative drug released. The XRD and DSC analyses demonstrated that the drug encapsulated in nanoparticles was present in the form of a molecular dispersion (dissolved state) in the polymer, whereas in microparticles, the drug was present in both molecular dispersion and crystalline forms. In conclusion, the solid-state drug-polymer solubility affects the nanoparticle characteristics, and thus could be used as an important preformulation parameter.

AB - Biodegradable nanoparticles formulated from poly(D,L-lactide-co-glycolide) (PLGA) and polylactide (PLA) polymers are being extensively investigated for various drug delivery applications. In this study, we hypothesize that the solid-state solubility of hydrophobic drugs in polymers could influence their encapsulation and release from nanoparticles. Dexamethasone and flutamide were used as model hydrophobic drugs. A simple, semiquantitative method based on drug-polymer phase separation was developed to determine the solid-state drug-polymer solubility. Nanoparticles using PLGA/PLA polymers were formulated using an emulsion-solvent evaporation technique, and were characterized for size, drug loading, and in vitro release. X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were used to determine the physical state of the encapsulated drug. Results demonstrated that the solid-state drug-polymer solubility depends on the polymer composition, molecular weight, and end-functional groups (ester or carboxyl) in polymer chains. Higher solid-state drug-polymer solubility resulted in higher drug encapsulation in nanoparticles, but followed an inverse correlation with the percent cumulative drug released. The XRD and DSC analyses demonstrated that the drug encapsulated in nanoparticles was present in the form of a molecular dispersion (dissolved state) in the polymer, whereas in microparticles, the drug was present in both molecular dispersion and crystalline forms. In conclusion, the solid-state drug-polymer solubility affects the nanoparticle characteristics, and thus could be used as an important preformulation parameter.

UR - http://www.scopus.com/inward/record.url?scp=3042601972&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042601972&partnerID=8YFLogxK

U2 - 10.1002/jps.20094

DO - 10.1002/jps.20094

M3 - Article

C2 - 15176068

AN - SCOPUS:3042601972

VL - 93

SP - 1804

EP - 1814

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 7

ER -