The effect of Ibuprofen–DEAE-Dextran nanoconjugates (surfactant solubilization) on the thermal properties and in vitro drug release kinetics of ibuprofen
Adeola T. Kola-Mustapha1 and Amos O. Abioye2.
Faculty of Pharmaceutical Sciences, University of Ilorin, Ilorin, Nigeria1; Leicester School of Pharmacy, De Montfort University, Leicester, UK2. *Corresponding author: Adeola T. Kola-Mustapha,Email: email@example.com, +2348033475485
Background: It has become increasingly desirable to overcome the low aqueous solubility of drug candidates and develop more novel and innovative formulation approaches to increase the dissolution rate of the poorly soluble drugs; due to significant difficulties presented by Active Pharmaceutical Ingredients (APIs) in drug product design and development. This work focused on the effect of stable amorphous ibuprofen-DEAE-Dextran nanoconjugates formulated in earlier studies via surfactant solubilization technique (organic solvent free process) on its physicochemical and drug release characteristics.
Methods: The nanoparticles were characterised via the Fourier Transform Infra-red (FTIR), Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), drug release profile and kinetics.
Results: The FTIR spectroscopic analysis revealed electrostatic, hydrophobic and hydrogen bonding interaction between solubilized ibuprofen and the cationic polymer (DEAE-Dextran) to form a new product (an amide). The DSC of the nanoconjugates exhibited broad and diffuse melting peaks which confirmed that the Ibuprofen-DEAE-Dextran nanoconjugates exist in amorphous state. Isothermal stability was suggested due to the disappearance of thermal decomposition peak of ibuprofen at 237.51 °C also disappeared in all the nanoconjugates. The TGA thermograms of the nanoconjugates exhibited two steps of weight loss profile due to the loss of free water and decomposition of the nanoconjugates. Marked enhancement of drug release was achieved by the nanoconjugates. The major mechanism of drug release from the nanoconjugates was by anomalous diffusion. Conclusions: This study therefore demonstrates the improved drug release profile of amorphous Ibuprofen-DEAE-Dextran nanoconjugates with potential application in the delivery of poorly soluble drug.
Key Words: Ibuprofen, surfactant solubilization, DEAE-Dextran, nanoconjugate and poorly soluble drug
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- Abioye AO, Kola-Mustapha AT and Ruparelia K (2014) Impact of in situ granulation and temperature quenching on crystal habit and micromeritic properties of ibuprofen-cationic dextran conjugate crystanules. International Journal of Pharmaceutics 462: 83-102.
- Abioye AO, Kola-Mustapha AT, Chi GT and Ilya S (2014) Quantification of in situ granulation-induced changes in pre-compression, solubility, dose distribution and intrinsic in vitro release characteristics of ibuprofen-cationic dextran conjugate crystanules, International Journal of Pharmaceutics 471: 453-477.
- Persson BH, Caram-Lelham NA, Sundelof LO (2000) Dextran Sulfate-Amphiphile Interaction: Effect of polyelectrolyte Charge Density and Amphiphile Hydrophobicity. Langmuir 16(2): 313-317.
- Cheow WS and Hadinoto K (2012) Self-Assembled Amorphous Drug-Polyelectrolyte Nanoparticle Complex with Enhanced Dissolution Rate and Saturation Solubility. J Coll Int Sci,. 367: 518-526.
- Barreiro-Iglesias R, Temchenko ML. Hatton TA, Concheiro A and Alvarez-Lorenzo, C., (2004) Solubilization and Stabilization of Camptothecin in Micellar Solutions of Pluronic-g-poly(acrylic acid) Copolymers. J Cont Rel 97(3): 537-549.
- Adams MLL and Kwon GSA (2003) Amphiphilic Block Copolymers for Drug J Pharm Sci,. 92:1343-1355.
- Jones M-C and Leroux J-C (1999) Polymeric Micelles-A New Generation of Colloidal Drug Carriers. Eur J Pharm Biopharm 48(2): 101-111.
- Abioye AO and Kola-Mustapha (2015) 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 (6): 2110-2131.
- Abioye AO, Armitage R and Kola-Mustapha AT, (2015) Thermodynamic Changes Induced by Intermolecular Interaction Between Ibuprofen and Chitosan: Effect on Crystal Habit, Solubility and In Vitro Release Kinetics of Ibuprofen, Pharm Res DOI 10.1007/s11095-015-1793-0. Available online 24th September, 2015.
- Kola-Mustapha AT and Abioye AO (2015) Formulation and Physical Characterization of Ibuprofen-DEAE-Dextran Nanoconjugates via Surfactant Solubilization West African Journal of Pharmacy 26 (2):1-10
- S. Pharmacopeia (2009) USP Pharmacist’s Pharmacopeia, United States Pharmacopeial Convention Rockville: S3/22-40
- Hadjiioannou TP, Cristian GD, Kouparris MA, and Macheras PE (1993) Quantitative Calculations in Pharmaceutical Practise and Research., New York: VCH Publishers Inc.
- Bourne DWA (2002) Pharmacokinetics, in Modern Pharmaceutics, G.S. Banker and C.T. Rhodes, Editors., Marcel Dekker Inc New York: 94-144.
- Higuchi T (1963) Mechanism of Sustained-Action Medication. Theoretical Analysis of Rate of Release of Solid Drugs Dispersed in Solid Matrices. J Pharm Sci 52(12): 1145-1149.
- Korsemeyer RW, Gurny R, Doelker E, Buri P, and Peppas PA (1983) Mechanism of Solute Release from Porous Hydrophilic Polymers. Int J Pharm 15(1): 25-35.
- Thakkar VTS, Soni PA, Parmar TG, Gohel MC and Ghandi TR (2009) Goodness-of-fit Model-Dependent Approach for Release Kinetics of Levofloxacin Hemihydrates Floating Tablet. Dissolution Technol 1: 35-39.
- Moore JW (1996) Mathematical Comparison of Dissolution Profiles. Drug Dev Ind Pharm 12: 969-992.
- Pillay J and Fassihi R (1998) Evaluation and Comparison of Dissolution Data Derived from Different Modified Release Dosage Forms: an Alternative Method. J Control Release 1998: 45-55.
- Harwood LM and Claridge TDW (1999) Introduction to Organic Spectroscopy. New York: Oxford University Press Inc.
- Coates J (2000) Interpretation of Infrared Spectra, A Practical Approach, in Encyclopedia of Analytical Chemistry, R.A. Meyers, Editor., John Wiley and Sons Ltd Chichester, UK: 10815-10837.
- Demirbile C and Dinc CO (2012) Synthesis of Diethylaminoethyl Dextran Hydrogel and its Heavy Metal Ion Adsorption Characteristics. Carbohydr Polym 90(2):1159-1167
- Matkovic SR, Valle GM, and Briand LE (2005) Quantitative Analysis of Ibuprofen in Pharmaceutical formulations through FTIR Spectroscopy. Lat Am Appl Res 35(3): 189-195.
- Nokhodchi AA, Jelvehgari OM (2010) Physico-Mechanical and Dissolution Behaviours of Ibuprofen Crystals Crystallized in the Presence of Various Additives. DARU 18(2): 74-83.
- British Pharmacopoeia Commission, British Pharmacopoeia 2012. Vol. 1. 2011, Norwich, Great Britain: Stationery Office Books.
- Kumar DPS, Subrata DC, Soumen CR (2012) Formulation and Evaluation of Solid Lipid Nanoparticles of A Poorly Water Soluble Model Drug, Ibuprofen. Int Res J Pharm 3(12): p. 132-137.
- Cardenas G and Miranda SP (2004) FTIR and TGA Studies of Chitosan Composite Films. J Chil Chem Soc 49(4): 291-295.
- Bottom R Ed. (2008) Thermogravimetric Analysis. Principles and Applications of Thermal Analysis, ed. P. Gabbott, Blackwell Publishing Ltd: Oxford. 484.
- Purcaru S-OI, Raneti M, Anuta C, Mircioiu V, and Belu I (2010) Study of Nimesulide Release from Solid Pharmaceutical Formulations in Tween 80 Solutions. Curr Health Sci J: 36(1).
- Siepmann J and Peppas NA (2001) Modeling of Drug Release from Delivery Systems based on Hydroxypropyl Methylcellulose (HPMC). Adv Drug Deliv Rev. 48: 139-157.
- Ritger PL and Peppas NA (1987) A Simple Equation For Description of Solute Release. I. Fickian and non-Fickian Release from Non-Swellable Devices in the Form of Slabs, Spheres, Cylinders or Discs. J Cont Rel 5: p23-36.
- Ritger PL and Peppas NA (1987) A Simple Equation for Description of Solute Release. II. Fickian and Anomalous Release from Swellable Devices. J Cont Rel 5: 37-42.