ORCID Profile
0000-0001-8856-0317
Current Organisation
University of South Australia
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Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 14-12-2019
Abstract: Supersaturated silica-lipid hybrid (super-SLH) drug carriers are a recent strategy to improve the drug loading of oral solid lipid based formulations, however they are yet to be studied in vivo. This study investigated the in vivo pharmacokinetics (PK) of super-SLH containing ibuprofen (IBU), as a model Biopharmaceutics Classification Scheme (BCS) class II drug, analyzing the influence of supersaturated drug loading on oral bioavailability and assessing in vitro-in vivo correlation (IVIVC). In addition, super-SLH was directly compared with spray-dried SLH and Nurofen to explore its potential advantages over the well-established and commercial formulations. Fasted male Sprague-Dawley rats were administered formulation suspensions (10 mg/kg IBU) via oral gavage, and blood s les were acquired and plasma was analyzed for IBU concentrations over 24 hours. In vivo, super-SLH with drug loads of 9.5 (99.5% saturated) and 19.3% w/w (227% saturated) achieved bioavailabilities equal to spray-dried SLH and 2.2-fold greater than Nurofen. This effect diminished for super-SLH with a drug load of 29.1% w/w (389% saturated), which exhibited a bioavailability of less than Nurofen due to its greater extent of supersaturation and larger content of crystalline IBU. The super-SLH containing 19.3% w/w IBU provided the greatest PK performance, achieving the same degree of bioavailability enhancement as spray-dried SLH and requiring 63% less formulation. A significant positive IVIVC was observed between the performances of the formulations. These findings indicate the potential of super-SLH as an improved oral solid lipid based formulation strategy for enhancing oral bioavailability of other BCS class II drugs.
Publisher: American Chemical Society (ACS)
Date: 03-03-2022
DOI: 10.1021/ACS.MOLPHARMACEUT.1C00781
Abstract: SBA-15 mesoporous silica (MPS) has been widely used in oral drug delivery however, it has not been utilized for solidifying lipid-based formulations, and the impact of their characteristic intrawall microporosity remains largely unexplored. Here, we derive the impact of the MPS microporosity on the
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.ADDR.2018.11.006
Abstract: Self-emulsifying drug delivery systems (SEDDS) offer potential for overcoming the inherent slow dissolution and poor oral absorption of hydrophobic drugs by retaining them in a solubilised state during gastrointestinal transit. However, the promising biopharmaceutical benefits of liquid lipid formulations has not translated into widespread commercial success, due to their susceptibility to long term storage and in vivo precipitation issues. One strategy that has emerged to overcome such limitations, is to combine the solubilisation and dissolution enhancing properties of lipids with the stabilising effects of solid carrier materials. The development of intelligent hybrid drug formulations has presented new opportunities to harness the potential of emulsified lipids in optimising oral bioavailability for lipophilic therapeutics. Specific emphasis of this review is placed on the impact of solidification approaches and excipients on the biopharmaceutical performance of self-emulsifying lipids, with findings highlighting the key design considerations that should be implemented when developing hybrid lipid-based formulations.
Publisher: International Association of Physical Chemists (IAPC)
Date: 17-07-2020
DOI: 10.5599/ADMET.830
Abstract: class="ADMETabstracttext" Lipid-based formulations (LBFs) are well-known to improve the oral bioavailability of poorly water-soluble drugs (PWSDs) by presenting the drug to the gastrointestinal environment in a molecularly dispersed state, thus avoiding the rate-limiting dissolution step. Risperidone and lurasidone are antipsychotics drugs which experience erratic and variable absorption, leading to a low oral bioavailability. The aim of this research was to develop and investigate the performance of risperidone and lurasidone when formulated as an emulsion and silica-lipid hybrid (SLH). Lurasidone and risperidone were dissolved in Capmul® MCM at 100% and 80% their equilibrium solubility, respectively, prior to forming a sub-micron emulsion. SLH microparticles were fabricated by spray-drying a silica stabilised sub-micron emulsion to form a solid powder. The performances of the formulations were evaluated in simulated intestinal media under digesting conditions, where the emulsion and SLH provided a 17-fold and 23-fold increase in LUR solubilisation, respectively. However, the performance of RIS was reduced by 2.2-fold when encapsulated within SLH compared to pure drug. Owing to its pKa, RIS adsorbed to the silica and thus, dissolution was significantly hindered. The results reveal that LBFs may not overcome the challenges of all PWSDs and physiochemical properties must be carefully considered when predicting drug performance.
Publisher: MDPI AG
Date: 21-07-2020
DOI: 10.3390/PHARMACEUTICS12070687
Abstract: The unique nanostructured matrix obtained by silica-lipid hybrids (SLHs) is well known to improve the dissolution, absorption, and bioavailability of poorly water-soluble drugs (PWSDs). The aim of this study was to investigate the impact of: (i) drug load: 3–22.7% w/w, (ii) lipid type: medium-chain triglyceride (Captex 300) and mono and diester of caprylic acid (Capmul PG8), and (iii) silica nanostructure: spray dried fumed silica (FS) and mesoporous silica (MPS), on the in vitro dissolution, solubilization, and solid-state stability of the model drug fenofibrate (FEN). Greater FEN crystallinity was detected at higher drug loads and within the MPS formulations. Furthermore, an increased rate and extent of dissolution was achieved by FS formulations when compared to crystalline FEN (5–10-fold), a commercial product APO-fenofibrate (2.4–4-fold) and corresponding MPS formulations (2–4-fold). Precipitation of FEN during in vitro lipolysis restricted data interpretation, however a synergistic effect between MPS and Captex 300 in enhancing FEN aqueous solubilization was attained. It was concluded that a balance between in vitro performance and drug loading is key, and the optimum drug load was determined to be between 7–16% w/w, which corresponds to (200–400% equilibrium solubility in lipid Seq). This study provides valuable insight into the impact of key characteristics of SLHs, in constructing optimized solid-state lipid-based formulations for the oral delivery of PWSDs.
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.IJPHARM.2020.119069
Abstract: Abiraterone acetate, marketed as Zytiga®, is an antiandrogen medication used in the treatment of prostate cancer. Abiraterone acetate is a BCS Class IV compound associated with several oral delivery challenges. Its low solubility and high lipophilicity lead to poor oral bioavailability (<10%) and a dramatic positive food effect (5-10-fold). Hence, a large dose of abiraterone acetate (1000 mg per day) is prescribed to patients who must fast for at least 1 h before and 2 h after administration. The recent expiry of Zytiga®s' patent has led to the emergence of publications describing improved oral formulation strategies for abiraterone acetate. This review aims to discuss the characteristics of abiraterone acetate that lead to its unfavorable oral delivery, examine the oral formulation strategies that have been applied, and to describe potential alternative oral formulation strategies that have been used for other BCS Class IV drugs, to determine the most valuable strategies to develop novel and improved alternatives to the current commercial product. Specific emphasis of this review is placed on enabling oral formulation strategies that can improve solubilization and bioavailability, reduce the clinical dose and remove the pharmaceutical food effect to ultimately provide prostate cancer patients with a more efficient formulation with greater patient compliance.
Publisher: American Chemical Society (ACS)
Date: 07-01-2019
Publisher: Elsevier BV
Date: 06-2020
Publisher: Wiley
Date: 26-04-2021
DOI: 10.1111/BCP.14856
Abstract: The consumption of caffeine has been linked to osteoporosis, believed to be due to enhanced bone resorption as a result of increased calcium excretion in the urine. However, the amount of calcium in the urine may not necessarily reflect the true effect of caffeine on calcium clearance. This study therefore examined the impact of high‐dose, short‐term caffeine intake on renal clearance of calcium, sodium and creatinine in healthy adults. In a double‐blind clinical study, participants chewed caffeine ( n = 12) or placebo ( n = 12) gum for 5 minutes at 2‐hour intervals over a 6‐hour treatment period (800 mg total caffeine). Caffeine increased renal calcium clearance by 77%. Furthermore, the effect was positively correlated with sodium clearance and urine volume, suggesting that caffeine may act through inhibition of sodium reabsorption in the proximal convoluted tubule. This study confirmed that caffeine does increase renal calcium clearance and fosters further investigation into safe consumption of caffeine.
Publisher: American Society for Microbiology
Date: 18-01-2022
DOI: 10.1128/AAC.01584-21
Abstract: Despite repeated malaria infection, in iduals living in areas where malaria is endemic remain vulnerable to reinfection. The Janus kinase (JAK1/2) inhibitor ruxolitinib could potentially disrupt the parasite-induced dysfunctional immune response when administered with antimalarial therapy.
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.EJPB.2017.12.012
Abstract: The method of supersaturation for achieving high drug loads in lipid-based formulations is under exploited and relatively unexplored, especially in the case of solid-state lipid-based formulations. Silica-lipid hybrids are solid-state lipid-based formulations designed for improving the oral delivery of poorly water-soluble drugs. However, their application to compounds of low potency and requiring large doses is limited by their low drug loading capacity. Here, an innovative technique to fabricate supersaturated silica-lipid hybrid formulations (super-SLH) has been established and the relationship between drug load and performance investigated. Using the model poorly water-soluble drug, ibuprofen, super-SLH was fabricated possessing drug loads ranging from 8 to 44% w/w, i.e. greater than the previously developed standard ibuprofen silica-lipid hybrids (5.6% w/w). Drug crystallinity of the encapsulated ibuprofen ranged from non-crystalline to part-crystalline with an increase in drug load. Super-SLH achieved improved rates and extents of dissolution when compared to pure ibuprofen, regardless of the drug load. The percentage increase in dissolution extent at 60 min varied from 200 to 600%. The results of the current study indicate that supersaturation greatly improves drug loading and that 16-25% w/w is the optimum loading level which retains optimal dissolution behaviour for the oral delivery of ibuprofen, which has the potential to be translated to other poorly water-soluble drugs.
Publisher: Mary Ann Liebert Inc
Date: 10-2022
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.IJPHARM.2022.121695
Abstract: The concomitant administration of oral drugs with food can result in significant changes in bioavailability, leading to variable pharmacokinetics and considerable clinical implications, such as over- or under-dosing. Consequently, there is increasing demand for bio-enabling formulation strategies to reduce variability in exposure between the fasted and fed state and/or mitigate the pharmaceutical food effect. The current review critically evaluates technologies that have been implemented to overcome the positive food effects of pharmaceutical drugs, including, lipid-based formulations, nanosized drug preparations, cyclodextrins, amorphisation and solid dispersions, prodrugs and salts. Additionally, improved insight into preclinical models for predicting the food effect is provided. Despite the wealth of research, this review demonstrates that application of optimal formulation strategies to mitigate the positive food effects and the evaluation in preclinical models is not a universal approach, and improved standardisation of models to predict the food effects would be desirable. Ultimately, the successful reformulation of specific drugs to eliminate the food effect provides a panoply of advantages for patients with regard to clinical efficacy and compliance.
Publisher: Elsevier
Date: 2020
Publisher: MDPI AG
Date: 14-01-2023
DOI: 10.3390/PHARMACEUTICS15010284
Abstract: Reformulating poorly water-soluble drugs as supersaturated lipid-based formulations achieves higher drug loading and potentially improves solubilisation and bioavailability. However, for the weak base blonanserin, silica solidified supersaturated lipid-based formulations have demonstrated reduced in vitro solubilisation compared to their liquid-state counterparts. Therefore, this study aimed to understand the influence of supersaturated drug load on blonanserin solubilisation from liquid and silica solidified supersaturated self-nanoemulsifying drug delivery systems (super-SNEDDS) during in vitro lipolysis. Stable liquid super-SNEDDS with varying drug loads (90–300% of the equilibrium solubility) were solidified by imbibition into porous silica microparticles (1:1 lipid: silica ratio). In vitro lipolysis revealed greater blonanserin solubilisation from liquid super-SNEDDS compared to solid at equivalent drug saturation levels, owing to strong silica-BLON/lipid interactions, evidenced by a significant decrease in blonanserin solubilisation upon addition of silica to a digesting liquid super-SNEDDS. An increase in solid super-SNEDDS drug loading led to increased solubilisation, owing to the increased drug:silica and drug:lipid ratios. Solidifying SNEDDS with silica enables the fabrication of powdered formulations with higher blonanserin loading and greater stability than liquid super-SNEDDS, however at the expense of drug solubilisation. These competing parameters need careful consideration in designing optimal super-SNEDDS for pre-clinical and clinical application.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 31-03-2020
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.IJANTIMICAG.2021.106443
Abstract: Cefepime-induced neurotoxicity (CIN) is an increasingly reported adverse event however, the toxicity threshold remains unclear. This study was conducted to provide a comprehensive examination of the most appropriate threshold for CIN, and evaluate the ability of current dosing regimens to attain therapeutic targets. Data of the incidence of CIN and cefepime plasma concentrations were collected retrospectively from patients administered cefepime. Population pharmacokinetic modelling was used to determine daily cefepime trough concentration (C In total, 102 cefepime courses were evaluated, with CIN reported in 10. ROC analyses showed that all cefepime pharmacokinetic parameters were strongly predictive of CIN. C The findings from this study provide evidence that cefepime exposure is highly predictive of CIN, with C
Publisher: Elsevier BV
Date: 02-2021
No related grants have been discovered for Hayley Schultz.