ORCID Profile
0000-0001-9777-0674
Current Organisation
The University of Auckland
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Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.JPBA.2009.02.032
Abstract: The chemical stability of ricobendazole (RBZ) was investigated using a stability-indicating high performance liquid chromatographic (HPLC) assay with ultraviolet detection. The degradation kinetics of RBZ in aqueous solution was evaluated as a function of pH, buffer strength and temperature. The oxidation reaction in hydrogen peroxide solution was also studied. Degradation products were analyzed by mass spectroscopy and degradation pathways are proposed. Degradation of RBZ followed pseudo first-order kinetics and Arrhenius behavior over the temperature range 24-55 degrees C. A V-shaped pH-rate profile over the pH range 2-12 was observed with maximum stability at pH 4.8. The shape of the pH-rate profile was rationalized by catalytic effects of various components in the solution on each RBZ species. At pH 11 the activation energy for hydrolysis was 79.5 kJ/mol, and phosphate catalysis was not observed. Oxidation occurred in hydrogen peroxide solutions and was catalyzed by the presence of copper (Cu(2+)) ions. Ricobendazole amine and albendazole sulfone were identified by MS assay to be the degradation products of hydrolysis and oxidation respectively.
Publisher: Informa UK Limited
Date: 23-03-2023
Publisher: Springer Science and Business Media LLC
Date: 24-08-2014
DOI: 10.1007/S00455-014-9558-1
Abstract: Citric acid is used in cough reflex testing in clinical and research settings to assess reflexive cough in patients at risk of swallowing disorders. To address a lack of knowledge in this area, this study investigated the stability and sterility of citric acid solutions. Triplicate solutions of citric acid (0.8 M) in isotonic saline were stored at 4 ± 2 °C for up to 28 days and analysed by high-performance liquid chromatography. Microbiological sterility of freshly prepared s les and bulk s les previously used for 2 weeks within the hospital was determined using a pour plate technique. Microbial survival in citric acid was determined by inoculating Staphylococcus aureus, Escherichia coli, or Candida albicans into citric acid solution and monitoring the number of colony-forming units/mL over 40 min. Citric acid solutions remained stable at 4 °C for 28 days (98.4 ± 1.8 % remained). The freshly prepared and clinical s les tested were sterile. However, viability studies revealed that citric acid solution allows for the survival of C. albicans but not for S. aureus or E. coli. The microbial survival study showed that citric acid kills S. aureus and E. coli but has no marked effect on C. albicans after 40 min. Citric acid s les at 0.8 M remained stable over the 4-week testing period, with viable microbial cells absent from s les tested. However, C. albicans has the ability to survive in citric acid solution if inadvertently introduced in practice. For this reason, in clinical and research practice it is suggested to use single-use aliquots prepared aseptically which can be stored for up to 28 days at 4 °C.
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.JCONREL.2013.11.022
Abstract: Microemulsions (MEs) have been studied extensively as colloidal carriers for the delivery of both water-soluble and lipid-soluble drugs. Our previous study showed that addition of water to ME formulations resulted in phase transition to either liquid crystal (LC) or coarse emulsion (CE). The aim of this study was to investigate whether these MEs could be used as drug delivery vehicles for prolonged release through in-situ phase transition following extravascular injection. Three ME formulations from the same pseudo-ternary phase diagram were investigated with respect to their phase transition behavior, and in-vivo drug release a coarse emulsion-forming ME (CE-ME), an oil rich LC-forming ME (LC-ME1), and an oil poor LC-forming ME (LC-ME2). CE-ME was a W/O ME and both LC-MEs were O/W type. The release profiles of (99m)Tc labeled MEs following subcutaneous (SC) injection in rabbits were investigated with gamma-scintigraphy. The CE-ME dispersed readily in water, forming a CE, whereas the LC-forming MEs formed 'depots' in water. Polarized microscopy revealed a LC boundary spontaneously formed at the water/ME interface for the LC-MEs with the LC-ME2 forming a substantially thicker LC layer. The CE resulting from the water-induced transition of the CE-forming ME had a higher viscosity than the MEs, but lower than the LCs resulted from LC-MEs. Compared to LC-ME1, LC-ME2 underwent more rapid phase transition and the resultant LC had significant higher viscosity. The LCs formed from both ME formulations exhibited pseudoplastic properties increasing the shear rate decreased the apparent viscosity exponentially. Following SC injection into the animal thigh, the LC-MEs had more prolonged release of (99m)Tc in a first-order manner, than CE-ME. The oil poor LC-ME2 had the slowest release with a t1/2 of 77min, 2.3 times longer than the oil rich LC-ME1 consistent with the thickness of LC layer formation observed in-vitro and their relative viscosities. In conclusion, the present in-vivo study has demonstrated the application of MEs as extravascular injectable drug delivery systems for sustained release. The retention of the vehicles at the injection site and the release rate were determined predominantly by their phase transition rather than ME type or oil content.
Publisher: American Chemical Society (ACS)
Date: 04-12-2020
DOI: 10.1021/ACS.JMEDCHEM.9B01694
Abstract: Cell-penetrating peptide conjugated peptide aldehydes
Publisher: Elsevier BV
Date: 05-2005
DOI: 10.1002/JPS.20282
Publisher: Elsevier BV
Date: 09-2005
DOI: 10.1016/J.JPBA.2005.03.010
Abstract: A simple, rapid and reliable high performance liquid chromatographic (HPLC) method has been developed and validated for simultaneous determination of ricobendazole (RBZ) and its main metabolite albendazole sulfone (ABZSO(2)) in sheep plasma using an isocratic system with UV detection. The method involved solid phase extraction followed by separation on a reversed phase C-18 column. Internal standard was selected by quantitative structure retention relationships (QSRRs) analysis. A method to optimize the composition of ternary components mobile phase with the assistance of multiple linear regression is described. Retention times were within 10 min. The calibration curves were linear over a concentration range of 10-1000 ng/ml for both RBZ and ABZSO(2) (r > 0.999). Intra-day relative standard deviation at low, medium and high concentration levels were <5.5% for RBZ and <4.6% for ABZSO(2) average accuracies were 98.3, 101.0 and 100.5% for RBZ and 101.0, 102.4 and 100.8% for ABZSO(2). The inter-day variations at the same concentrations were <5.9% for RBZ and <6.4% for ABZSO(2). The extraction recoveries at these concentrations for RBZ, ABZSO(2) and the internal standard were all over 96%. The limit of detection and limit of quantitation were 2.4 and 7.1 ng/ml, respectively for RBZ, and 10ng/ml for both analytes.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.JPBA.2009.06.046
Abstract: The aim of this study was to develop a stability-indicating HPLC assay for the determination of penethamate (PNT), an ester prodrug of benzylpenicillin (BP), in aqueous solutions. The method was validated by subjecting PNT to forced decomposition under stress conditions of acid, alkali, water hydrolysis and oxidation. A quenching solution was developed to limit degradation to negligible levels before and during the analysis. Both PNT and BP were simultaneously determined and separated in presence of degradation products on a C(18) column using a mobile phase consisting of methanol-acetonitrile-acetate buffer. Different degradation products were formed in the stress conditions. The peak purity indexes of PNT and BP obtained by diode array detection were >0.999, confirming the absence of other co-eluting substances. The assay was linear for both analytes in the concentration range 1-100 microg mL(-1). The LOD and LOQ of PNT were 0.03 and 0.09 microg mL(-1) respectively. Degradation of PNT followed pseudo-first-order kinetics with t(1/2) of 43.6 min at pH 2.01 and 4.2 min at pH 9.31. In addition, the absence of BP in the acidic solutions of PNT emphasises the futility of monitoring BP to assess the stability of PNT. In conclusion, the assay is rapid and stability-indicating with adequate precision and accuracy, and in conjunction with the quenching solution, can be used for stability studies of PNT with simultaneous quantitation of BP. The degradation studies provide useful information for formulation development of PNT.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.IJPHARM.2016.03.044
Abstract: This paper describes a novel method to improve drug retention in liposomes for the poorly water-soluble (lipophilic) model drug asulacrine (ASL). ASL was loaded in the aqueous phase of liposomes and the effects of aging conditions and drug loading levels on drug retention were investigated using an in vitro bio-relevant drug release test established in this study. The status of intra-liposomal drug was investigated using differential scanning calorimetry (DSC) and cryo-transmission electron microscopy (cryo-TEM). Pharmacokinetics and venous tolerance of the formulations were simultaneously studied in rabbits following one-hour intravenous infusion via the ear vein. The presence of glucose during aging was found to be crucial to accelerate drug precipitation and to stabilize the liposomal membrane with high drug loading (8.9% over 4.5% w/w) as a prerequisite. Although no drug crystals were detected, DSC showed a lower phase-transition peak in the glucose-assisted aged ASL-liposomes, indicating interaction of phospholipids with the sugar. Cryo-TEM revealed more 'coffee bean' like drug precipitate in the ASL-liposomes aged in the glucose solution. In rabbits, these liposomes gave rise to a 1.9 times longer half-life than the fresh liposomes, with no venous irritation observed. Inducing and stabilizing drug precipitation in the liposome cores by aging in the presence of sugar provided an easy approach to improve drug retention in liposomes. The study also highlighted the importance of bio-relevance of in vitro release methods to predict in vivo drug release.
Publisher: Elsevier BV
Date: 09-2010
DOI: 10.1016/J.IJPHARM.2010.07.002
Abstract: Post-injection precipitation may cause poor and erratic drug absorption and tissue irritation at the injection site. Tissue tolerance and pharmacokinetics of a low pH ricobendazole (RBZ) injectable containing 20% hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were simultaneously investigated after subcutaneous injection in sheep compared to a reference formulation without HP-beta-CD. Each animal received a RBZ containing formulation on one side of the back and the respective vehicle on the contralateral side. The HP-beta-CD vehicle showed good tissue tolerance and the acidic solution caused minimal injection site reactions. Both RBZ containing formulations caused pain on injection and tissue histological changes in some animals. Lack of elevation of plasma creatine kinase indicated that none of the formulations caused significant damage to the underlying muscle tissue. Compared to the reference formulation, AUC and C(max) of the HP-beta-CD formulation were 1.6 and 2.2 times higher, respectively, whereas t(max), MRT and t(1/2) were significantly shorter suggesting faster and greater absorption of RBZ in the presence of HP-beta-CD. This was attributed to the effect of inhibition of post-injection drug precipitation and drug absorption enhancement of HP-beta-CD. In conclusion, HP-beta-CD was shown to be a tissue-compatible excipient with potential to inhibit post-injection precipitation and increase absorption of poorly water soluble drugs. Additionally, the HP-beta-CD formulation showed promise as an injectable that potentially minimizes irritation by reducing the dose required.
Publisher: MDPI AG
Date: 28-03-2022
DOI: 10.3390/PHARMACEUTICS14040726
Abstract: Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by thin film hydration method and statistically optimised. The niosomes were characterised for size, zeta potential, morphology and entrapment efficiency. Ex vivo permeation and deposition studies were conducted using full-thickness human skin. Cell viability, lipid peroxidation, antioxidant enzyme activities after UVA-irradiation and cellular uptake were determined. The optimised niosomes were spherical and had a relatively uniform size of 235.4 ± 15.64 nm, with a zeta potential of −45.2 ± 0.03 mV and an EE of 53.05 ± 4.46%. The niosomes effectively prolonged drug release and demonstrated much greater skin penetration and deposition than free EGCG. They also increased cell survival after UVA-irradiation, reduced lipid peroxidation, and increased the antioxidant enzymes’ activities in human dermal fibroblasts (Fbs) compared to free EGCG. Finally, the uptake of niosomes was via energy-dependent endocytosis. The optimised niosomes have the potential to be used as a dermal carrier for antioxidants and other therapeutic compounds in the pharmaceutical and cosmetic industries.
Publisher: Informa UK Limited
Date: 23-06-2011
DOI: 10.3109/03639045.2011.590497
Abstract: Penethamate (PNT) is a diethylaminoethyl ester prodrug of benzylpenicillin used to treat bovine mastitis via the intramuscular route. Because of its instability, PNT products must be reconstituted before administration and the reconstituted injection has a short shelf life (7 days at 2-8°C). The purpose of this paper was to investigate whether the stability of PNT can be improved in order to achieve a chemically stable ready-to-use aqueous-based PNT formulation or at least to extend the shelf life of the reconstituted suspension. A chemical stability study of PNT in aqueous-based solutions as a function of pH, buffer strength, solvent mixtures and temperature, supported by studies of its solubility in mixed solvents, allowed predictions of the shelf life of PNT solution and suspension formulations. PNT degraded in aqueous solutions by several pathways over the pH range 2.0-9.3 with a V-shaped pH-rate profile and a minimum pH of around 4.5. The stability of PNT solutions in mixed solvents was greater than in aqueous solutions. For ex le, in propylene glycol:citrate buffer (60:40, v/v, pH 4.5), the half-life of PNT was 4.3 days compared with 1.8 days in aqueous buffer. However, solubility of PNT in the mixed solvent was higher than that in aqueous solution and this had an adverse effect on the stability of suspensions. By judicious choosing of pH and mixed solvent, it is possible to achieve a storage life of a PNT suspension of 5.5 months at 5°C, not sufficient for a ready-to-use product but a dramatic improvement in the storage life of the reconstituted product.
Publisher: Springer Science and Business Media LLC
Date: 30-10-2014
DOI: 10.1007/S11095-014-1551-8
Abstract: To develop a liposomal system with high drug loading (DL) for intravenous (i.v.) delivery of a poorly water-soluble basic drug, asulacrine (ASL). A thin-film hydration and extrusion method was used to fabricate the PEGylated liposomal membranes followed by a freeze and thaw process. A novel active drug loading method was developed using ammonium sulphate gradient as an influx driving force of ASL solubilized with sulfobutyl ether-β-cyclodextrin (SBE-β-CD). DL was maximized by optimizing liposomal preparation and loading conditions. Pharmacokinetics was evaluated following i.v. infusion in rabbits. Freeze-thaw resulted in unilamellar liposome formation (180 nm) free of micelles. Higher DL was obtained when dialysis was used to remove the untrapped ammonium sulphate compared to ultracentrifuge. The pH and SBE-β-CD level in the loading solution played key roles in enhancing DL. High DL ASL-liposomes (8.9%w/w, drug-to-lipid mole ratio 26%) were obtained with some drug "bundles" in the liposomal cores and were stable in a 5% glucose solution for >80 days with minimal leakage (<2%). Surprisingly, following administration of ASL-liposomes prepared with or without SBE-β-CD, the half-lives were similar to the drug solution despite an increased area under the curve, indicating drug leakage from the carriers. High liposomal DL was achieved with multiple strategies for a poorly-water soluble weak base. However, the liposomal permeability needed to be tailored to improve drug retention.
Publisher: Informa UK Limited
Date: 27-10-2021
Publisher: Elsevier BV
Date: 11-2005
DOI: 10.1016/J.IJPHARM.2005.08.012
Abstract: A simple in vitro method for the detection of precipitation using 96-well microplates and a SpectraMax Plus microtiter plate reader has been developed and described. The method requires only small amount of drug and is, therefore, potentially applicable in early pre-formulation. The method is based on opacity changes that occur with precipitation and yields several descriptive parameters, onset time (Tonset), maximum rate (Vmax) and the time to reach Vmax (Tmax). Using these parameters, potential parenteral formulations can be ranked by their tendency to precipitate on dilution. We report use of this method and ranking of potential formulations of ricobendazole (RBZ), a poorly soluble anthelmintic, in various solvent systems. Detection at 500 nm was more sensitive than a wavelength of 550 nm and increased temperature (37 degrees C compared with 25 degrees C) accelerated precipitation. Results demonstrated the method was simple, descriptive and objective in the detection of precipitation of ricobendazole formulation on dilution and pH shift.
No related grants have been discovered for Zimei Wu.