Browsing by Author "Abioye, Amos Olusegun"
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Item Controlled electrostatic self-assembly of ibuprofen-cationic dextran nanoconjugates prepared by low energy green process – a novel delivery tool for poorly soluble drugs(Pharmaceutical Research, 2015-06) Abioye, Amos Olusegun; Kola-Mustapha, AdeolaPURPOSE: 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, (1)H NMR and (13)C 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/dm(3) 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.Item Ex vivo skin permeation and retention studies on chitosan-ibuprofen-gellan ternary nanogel prepared by in situ ionic gelation technique – a tool for controlled transdermal delivery of ibuprofen(International Journal of Pharmaceutics, 2015-07) Abioye, Amos Olusegun; Issah, Sureya; Kola-Mustapha, Adeola TawakalituThe chemical potentials of drug-polymer electrostatic interaction have been utilized to develop a novel ternary chitosan-ibuprofen-gellan nanogel as controlled transdermal delivery tool for ibuprofen. The ternary nanogels were prepared by a combination of electrostatic nanoassembly and ionic gelation techniques. The electrostatic and hydrophobic interactions as well as hydrogen bonding between ibuprofen and chitosan were confirmed with FTIR, while DSC, TGA and SEM confirmed the physical state, thermal and morphological characteristics, respectively. The ex vivo delivery of ibuprofen onto and across the skin was evaluated based on system specific drug release parameters such as steady state permeation rate, permeability coefficient, permeability enhancement ratio, skin/gel partition coefficient, diffusion coefficient, lag time and release rate constant and mechanisms of release were determined using mathematical models. Interaction between ibuprofen and chitosan produced new spherical eutectic nanoconjugates with remarkable decrease in particle size of ibuprofen from 4580 (length-to-breadth aspect ratio) to a minimum of 14.15 nm (324-times), and thermally stable amorphous characteristics. The nanogels exhibited significant elastic and pseudoplastic characteristics dictated by the concentration of chitosan with maximum swelling capacity of 775% w/w at 6.55 mM chitosan compared with 281.16 and 506.50% for plain gellan and control ibuprofen hydrogel, respectively. Chitosan enhanced the skin penetration, permeability and the rate of transdermal release of ibuprofen by a factor of 4, dictated by the extent of ibuprofen-chitosan ionic interaction and its concentration. The major mechanism of ibuprofen release through the pig skin was drug diffusion however drug partition and matrix erosion also occurred. It was evident that ternary nanogels are novel formulations with potential application in controlled transdermal delivery of ibuprofen.Item Formulation studies on Ibuprofen sodium-cationic dextran conjugate: Effect on tabletting and dissolution characteristics of ibuprofen.(Drug Development and Industrial Pharmacy, 2016) Abioye, Amos Olusegun; Kola-Mustapha, AdeolaThe effect of electrostatic interaction between ibuprofen sodium (IbS) and cationic diethylaminoethyl dextran (Ddex), on the tableting properties and ibuprofen release from the conjugate tablet was investigated. Ibuprofen exhibits poor flow, compaction (tableting) and dissolution behavior due to its hydrophobic structure, high cohesive, adhesive and viscoelastic properties therefore it was granulated with cationic Ddex to improve its compression and dissolution characteristics. Electrostatic interaction and hydrogen bonding between IbS and Ddex was confirmed with FT-IR and DSC results showed a stepwise endothermic solid-solid structural transformation from racemic to anhydrous forms between 120 and 175 °C which melted into liquid form at 208.15 °C. The broad and diffused DSC peaks of the conjugate granules as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. It was evident that Ddex improved the flowability and densification of the granules and increased the mechanical and tensile strengths of the resulting tablets as the tensile strength increased from 0.67 ± 0.0172 to 1.90 ± 0.0038 MPa with increasing Ddex concentration. Both tapping and compression processes showed that the most prominent mechanism of densification were particle slippage, rearrangement and plastic deformation while fragmentation was minimized. Ddex retarded the extent of dissolution in general, indicating potentials for controlled release formulations. Multiple release mechanisms including diffusion; anomalous transport and super case II transport were noted. It was concluded that interaction between ibuprofen sodium and Ddex produced a novel formulation with improved flowability, tableting and dissolution characteristics with potential controlled drug release characteristics dictated by Ddex concentration.Item Impact of in situ granulation and temperature quenching on crystal habit and micromeritic properties of ibuprofen-cationic dextran conjugate crystanules(International Journal of Pharmaceutics, 2014) Abioye, Amos Olusegun; Kola-Mustapha, Adeola; Ruparelia, KetanIbuprofen was recrystallized in the presence of aqueous solution of cationic dextran derivative, Diethylaminoethyl Dextran (Ddex) using the melt in-situ granulation-crystallization technique in order to produce a stable amorphous ibuprofen-Ddex conjugates with improved morphological, micromeritic and thermo-analytical characteristics without the use of organic solvent. Ddex was used in this study because of its ability to form conjugates with various drug molecules and enhance their physicochemical characteristics and therapeutic activities. Cationic dextrans are also biocompatible and biodegradable. Mechanism of conjugation as well as the impact of conjugation on the ibuprofen crystal habit was investigated. Gaussian type normal particle size distribution was obtained and the size of the crystals in the crystanule conjugates decreased steadily, with increasing concentration of Ddex, to a minimum of 480 nm (440 folds reduction, p < 0.05, n = 20) at Ddex molar concentration of 0.01M. FT-IR spectra showed electrostatic interaction and hydrogen bonding between ibuprofen and Ddex which was confirmed with the 1H NMR and 13H NMR spectra. DSC curves exhibited single peaks from the binary ibuprofen-Ddex conjugate crystanules suggesting compatibility and formulation of an eutectic product. The conjugate crystanules showed broad and diffuse endothermic peaks with a glass transition temperature (Tg) 58.3 and 59.14 °C at Ddex molar concentrations of 1.56 X 10-4 and 3.125 X 10-4 mM respectively confirming the existence of ibuprofen-Ddex crystanule conjugates in amorphous state. Higher concentrations of Ddex decreased Tg steadily. TGA curves showed first order degradation at low molar concentrations of Ddex up to 3.125 X 10-4 mM which coincides with the critical granular concentration of the crystanules with higher concentrations exhibited second order degradation profile. This study provides the basis for the development of stable amorphous drug-polymer conjugates with potential practical application in controlled and extended drug release formulationsItem Polymer-Drug Nanoconjugate – An Innovative Nanomedicine: Challenges and Recent Advancements in Rational Formulation Design for Effective Delivery of Poorly Soluble Drugs(Pharmaceutical Nanotechnology (Betham Science), 2016) Abioye, Amos Olusegun; Chi, George Tangyie; Kola-Mustapha, Adeola T; Ruparelia, Ketan; Beresford, Ken; Aroo, RandolphBackground: Over the last four decades, the use of water soluble polymers in rational formulation design has rapidly evolved into valuable drug delivery strategies to enhance the safety and therapeutic effectiveness of poorly soluble drugs, particularly anticancer drugs. Novel advances in polymer chemistry have provided new generations of well defined polymeric architectures for specific applications in polymer-drug conjugate design. However, total control of crucial parameters such as particle size, molecular weight distribution, polydispersity, localization of charges, hydrophilic-lipophilic balance and non site-specific coupling reactions during conjugation has been a serious challenge. Objective: This review briefly describes the current advances in polymer-drug nanoconjugate design and various challenges hindering their transformation into clinically useful medicines. Method: Existing literature was reviewed. Results: This review provides insights into the significant impact of covalent and non-covalent interactions between drug and polymer on drug loading (or conjugation) efficiency, conjugate stability, mechanism of drug release from the conjugate and biopharmaceutical properties of poorly soluble drugs. The utility values and application of Quality by Design principles in rational design, optimization and control of the Critical Quality Attributes (CQA) and Critical Process Parameters (CPP) that underpin the safety, quality and efficacy of the nanoconjugates are also presented. Conclusion: It was apparent that better understanding of the physicochemical properties of the nanoconjugates as well as the drug-polymer interaction during conjugation process is essential to be able to control the biodistribution, pharmacokinetics, therapeutic activity and toxicity of the nanoconjugates which will in turn enhance the prospect of successful transformation of these promising nanoconjugates into clinically useful nanomedicines.Item 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, 2014) Abioye, Amos Olusegun; Kola-Mustapha, Adeola; Chi, George Tangyie; Ilya, SundayItem Thermodynamic Changes Induced by Intermolecular Interaction Between Ibuprofen and Chitosan: Effect on Crystal Habit, Solubility and In Vitro Release Kinetics of Ibuprofen(Pharmaceutical Research, 2016-02) Abioye, Amos Olusegun; Armitage, Rachel; Kola-Mustapha, Adeola TawakalituThe direct impact of intermolecular attraction between ibuprofen and chitosan on crystal behaviour, saturated solubility and dissolution efficiency of ibuprofen was investigated in order to expand the drug delivery strategy for ibuprofen. METHODS: Amorphous nanoparticle complex (nanoplex) was prepared by controlled drug-polymer nanoassembly. Intermolecular attraction was confirmed with surface tension, conductivity measurements and FTIR spectroscopy. The nanoplex was characterized using DSC, TGA and SEM. The in vitro release kinetics and mechanism of drug release were evaluated using mathematical models. RESULTS: The cmc of ibuprofen decreased significantly in the nanoplex (1.85 mM) compared with pure ibuprofen (177.62 mM) suggesting a remarkable affinity between the chitosan and ibuprofen. The disappearance of ibuprofen melting peak in the nanoplex and the broadened DSC endothermic peaks of the nanoplex indicate formation of eutectic amorphous product which corresponded to higher saturated solubility and dissolution velocity. Ibuprofen (aspect ratio 5.16 ± 1.15) was converted into spherical nanoparticle complex with particle size of 14.96 ± 1.162-143.17 ± 17.5247 nm (36-345 folds reduction) dictated by chitosan concentration. Pure ibuprofen exhibited burst release while the nanoplexes showed both fast and extended release profiles. DE increased to a maximum (81.76 ± 2.1031%) with chitosan concentrations at 3.28 × 10-3 g/dm3, beyond which retardation occurred steadily. Major mechanism of drug release from the nanoplex was by diffusion however anomalous transport and super case II transport did occur. CONCLUSION: Ibuprofen-chitosan nanoplex exhibited combined fast and extended release profile dictated by chitosan concentration. This study demonstrated the potential application of drug-polymer nanoconjugate design in multifunctional regulated drug delivery.