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Controlled Electrostatic Self-Assembly of Ibuprofen-Cationic Dextran Nanoconjugates Prepared by low Energy Green Process – a Novel Delivery Tool for Poorly Soluble Drugs

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Abstract

Purpose

The direct effect of electrostatic interaction between ibuprofen and cationic dextran on the system-specific physicochemical parameters and intrinsic dissolution characteristics of ibuprofen was evaluated in order to develop drug-polymer nanoconjugate as a delivery strategy for poorly soluble drugs.

Methods

Amorphous ibuprofen-DEAE dextran (Ddex) nanoconjugate was prepared using a low energy, controlled amphiphile-polyelectrolyte electrostatic self-assembly technique optimized by ibuprofen critical solubility and Ddex charge screening. Physicochemical characteristics of the nanoconjugates were evaluated using FTIR, DSC, TGA, NMR and SEM relative to pure ibuprofen. The in vitro release profiles and mechanism of ibuprofen release were determined using mathematical models including zero and first order kinetics; Higuchi; Hixson-Crowell and Korsmeyer-Peppas.

Results

Electrostatic interaction between ibuprofen and Ddex was confirmed with FT-IR, 1H NMR and 13C NMR spectroscopy. The broad and diffused DSC peaks of the nanoconjugate as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. Low concentrations of Ddex up to 1.0 × 10−6 g/dm3 enhanced dissolution of ibuprofen to a maximum of 81.32% beyond which retardation occurred steadily. Multiple release mechanisms including diffusion; discrete drug dissolution; anomalous transport and super case II transport were noted.

Conclusions

Controlled assembly of ibuprofen and Ddex produced a novel formulation with potential extended drug release dictated by Ddex concentration.

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Abbreviations

ANOVA:

Analysis of variance

CAPESA:

Controlled amphiphile-polyelectrolyte electrostatic assembly

CE:

Conjugation efficiency

Ddex:

Diethyaminoethyl Dextran

DE:

Dissolution efficiency

DSC:

Differential scanning calorimetry

FT-IF:

Fourier Transform Infra-Red spectroscopy

Ibu:

Ibuprofen

MANOVA:

Multivariate analysis of variance

MDR:

Mean dissolution rate

MDT:

Mean dissolution time

NMR:

Nuclear Magnetic Resonance

SEM:

Scanning Electron Microscopy

TGA:

Thermal Gravimetric Analysis

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Acknowledgements

The authors are thankful to Dr. Ketan Ruparelia and Mrs Rachel Armitage for technical and scientific assistance on NMR and SEM respectively.

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Authors and Affiliations

  1. Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK

    Amos Olusegun Abioye & Adeola Kola-Mustapha

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  1. Amos Olusegun Abioye
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  2. Adeola Kola-Mustapha
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Correspondence to Amos Olusegun Abioye.

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Abioye, A.O., Kola-Mustapha, A. Controlled Electrostatic Self-Assembly of Ibuprofen-Cationic Dextran Nanoconjugates Prepared by low Energy Green Process – a Novel Delivery Tool for Poorly Soluble Drugs. Pharm Res 32, 2110–2131 (2015). https://doi.org/10.1007/s11095-014-1603-0

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  • DOI: https://doi.org/10.1007/s11095-014-1603-0

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