Browsing by Author "Ruparelia, Ketan"

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    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, Ketan
    Ibuprofen 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 formulations
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    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, Randolph
    Background: 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.