Dr Yousuf Mohammed

Research Fellow

The University of Queensland Diamantina Institute
Faculty of Medicine
y.mohammed@uq.edu.au
+61 7 344 37485
0433853534

Overview

Dr Yousuf Mohammed completed his PhD in pharmaceutics and skin drug delivery under the guidance of Associate prof Heather Benson, Prof Michael Roberts and Associate prof Tarl Prow. He has been working within the field of skin delivery at the Therapeutics Research Centre, University of Queensland - School of Medicine since 2012. His current research includes managing a five-year (2018-2023) US FDA funded project titled Bioequivalence of Topical products: Elucidating the Thermodynamic and Functional Characteristics of Compositionally Different Topical Formulations as a Principle Investigator and managing the five-year project (2014-2019) Characterization of Critical Quality Attributes for Semisolid Topical Drug Products as a Co-investigator. These projects aims to improve current regulatory guidelines for topical and transdermal semisolid products. Over the last 6 years, his work has been focused on skin penetration and skin toxicology of drugs and xenobiotics including nanoparticulate materials.

Research Interests

  • Bioequivalence of Topical products: Elucidating the sensorial and functional characteristics of Topical Formulations
    In addition to the defined therapeutic effect caused by an active drug in a product, there is also a placebo and, potentially, a nocebo effect associated with those products. In topical products, these latter effects may account from 30% to 50% of the overall response for some products. They may also explain why some topical products with apparently identical bioavailability are associated with different patient outcomes. This application seeks to address the question of when do subtle excipient and manufacturing changes in a topical product cause a sensorial sensation by subjects that the “feel” of a product has changed either before and/or after it is applied to human skin. A second question is whether the “feel” of a product both before and after application can be quantified by instrumental rheology, tribology and texture analysis methods and whether these, in turn, can be related to the reported sensorial behaviour. We will manufacture topical formulations that systematically vary in Q1, Q2, and/or Q3 attributes and have large and borderline perceptive differences. We will then characterized these products using a range of rheology, tribology and texture analysis methods. In parallel, these products will be evaluated by perceptive testing focus groups, with controls, of their sensorial characterisation of the ‘feel’ of the products. We will then relate these sensorial findings with the variations in formulation nature, composition and manufacture, and their resulting instrumental test results. Our goals are, firstly, to understand the relationships between product nature, instrumental findings and sensorial analyses and, secondly, to derive criteria for instrument tests that indicates what product composition subjects suggest do not differ, uncertain if they differ and do differ in their sensorial behaviour. It is hoped that we can define the simplest, robust test that accurately and robustly is in line with sensory perceptions. A range of statistical methods, including (potentially) sophisticated, machine learning and deep learning tools will then be used to model the most appropriate instrumental analysis that can, with reasonable confidence predict perceptive attributes. A key outcome is a potential regulatory guideline advocating that generic products should exhibit similar sensorial behaviour as a reference listed drug product, giving boundaries in rheology, tribology and texture analysis as defined by Q1, Q2 and Q3 differences when that sensorial behaviour between topical products is likely to be different.
  • Bioequivalence of Topical products: Elucidating the Thermodynamic and Functional Characteristics of Compositionally Different Topical Formulations
    The general requirements for generics to be considered are that the product is off-patent, contains an active ingredient in a previously approved medicine and is shown to be bioequivalent to that previously approved medicine. The fundamental forces governing the effects of topical drugs applied to the skin can be summed up in three distinct dimensions. 1. The interaction of the active pharmaceutical ingredient (API) with the excipients (formulation factors, solubility), 2. API with the skin (thermodynamic and pharmacodynamic activity) and 3. Excipient with the skin (penetration enhancement, diffusivity, irritancy). A thoughtful appreciation followed by a thorough understanding and then careful deliberations can help mitigate a number of failure modes that can arise from these three dimensions and result in disapproval of generic drug applications. However, there is an elusive fourth dimension, the psychorheology or the sensory/perceptive judgement of the rheological properties (and other organoleptic properties) that dictates the end user/consumers final acceptance of the product. Through this project we aim to develop meaningful risk mitigating methods and their scientific basis. These will encompass considering product behaviour during various stages of development/manufacturing, all the way to looking at the metamorphosing product as it is being applied to the treatment site on the skin. The development of generic topical products has been hampered by factors such as expensive clinical trials for BE assessment and application costs which get blown out due to the case by case assessment of applications. A burdensome application package is generally needed that wastes valuable resources and time on both sides of the coin. This project will ensure the much needed theoretical and practical framework that can enable a thorough yet efficient assessment of topical generic product applications.
  • Characterization of Critical Quality Attributes for Semisolid Topical Drug Products
    This US FDA funded project aims to understand the formulation-drug-skin interactions. Certain physicochemical attributes of a pharmaceutical product can be deemed as Critical Quality Attributes based on their influence of the product performance. This 5 year project goes into 16 different quality attributes and tests for their role in the performance of topical products using 22 different tests and numerous instruments and methods.
  • Toxicology of topically applied nanoparticles
    The safety of nanoparticles used in sunscreens has been a controversial international issue in recent years, in part because previous animal exposure studies generally found much higher skin absorption of zinc from dermal application of ZnO sunscreens than human studies. Our group’s work for the last several years has challenged these false alarms and through evidence based volunteer studies, provided the vital confidence boosting evidence for safe use of sunscreens. This is particularly relevant as the typical exposure to dangerous UV radiations has been on the rise.

Research Impacts

Dr Yousuf Mohammed completed his PhD in pharmaceutics and skin drug delivery under the guidance of Associate prof Heather Benson, Prof Michael Roberts and Associate prof Tarl Prow. He has been working within the field of skin delivery at the Therapeutics Research Centre, University of Queensland - School of Medicine since 2012. His current research includes managing a five-year (2018-2023) US FDA funded project titled Bioequivalence of Topical products: Elucidating the Thermodynamic and Functional Characteristics of Compositionally Different Topical Formulations as a Principle Investigator and managing a four-year (2019-2023) US FDA funded project titled Bioequivalence of Topical products: Elucidating the sensorial and functional characteristics of Topical Formulations as a Principle Investigator. He is also currently managing the five-year project (2014-2019) Characterization of Critical Quality Attributes for Semisolid Topical Drug Products as a Co-investigator. These projects aims to improve current regulatory guidelines for topical and transdermal semisolid products in its second year of No Cost Extension. Over the last 6 years, his work has been focused on skin penetration and skin toxicology of drugs and xenobiotics including nanoparticulate materials.

Working on the US FDA project over the last two years has given an opportunity to showcase real world translational research. The work Yousuf and team has done has led to FDA guidance for Acyclovir creams which highlight the novel methods developed as a part of the work carried out locally in Brisbane in between TRI and other labs in the St Lucia campus.

Role of dispensers on physicochemical properties of the cream when dispensed. Difference in product performance upon dispensing from different dispensers was first identified and reported by our group and the change in cream product guidance based on this work is one of the biggest achievements. Our work over the last couple of years and specifically in the current year (July 2016- June 2017) has also identified skin and drug properties that determine product performance. Of special mention is our work on testing IVPT performance with different doses, different skin membrane types and different sampling protocols and different study durations. This a part of grant’s Aim 3 where we proposed to develop ideal IVPT conditions based on careful literature review as well as clearly thought-out experiments to investigate each parameter that can effect a products performance. Our IVPT studies have also included developing in-use product application and testing protocols and have assessed direct comparisons of CQAs with product performance.

Locally within the Australian topical and consumer product regulatory scene, Dr Mohammed’s work published in the Journal of Investigative dermatology has helped dispel false alarms regarding the safety and toxicity of ZnO nanoparticles. The story was captured by numerous (>400) printed and online media articles. This work, coming out at the peak of summer in Australia led to improved consumer confidence regarding better sun protection habits.

Qualifications

  • Doctor of Philosophy, Curtin University
  • Master of Pharmacy, Curtin University

Publications

View all Publications

Supervision

View all Supervision

Available Projects

  • This project is an exceptionally innovative combination of pharmaceutical science, materials science, nanotechnology, and clinical science to develop a state-of-the art drug delivery technology for an optimal treatment and overdose risk management of hghly potent medicinal compunds. The project will trigger a paradigm shift towards safer dosing of abuse and misuse prone drugs, which suffer from unreliable bioavailability due to solubility or permeation challenges.

  • The purpose of this project is to support the research necessary to elucidate how systematic alterations to the qualitative (Q1) and/or quantitative (Q2) composition of topical formulations impacts their physical, structural, and functional properties. A key aspect of the research relates to understanding how the thermodynamic properties of a topical dosage form change as it undergoes metamorphosis during dose application and drying on the skin, how the drug's thermodynamic activity profile during the metamorphosis of the dosage form may compare between compositionally different (non-Q1 and/or non-Q2) topical formulations, and how these and other forces may modulate the rate and extent to which topically applied drugs may become available at or near their site(s) of action in the skin. Another key aspect of the research relates to identifying and understanding other potential failure modes for bioequivalence (BE) and/or therapeutic equivalence (TE) (e.g., differences in irritation potential) that may arise between compositionally different (non-Q1 and/or non-Q2) topical formulations.

  • The purpose of this project is to support research relevant to topical semisolid drug products that will help elucidate the relationship between a product's quality attributes and its functional properties. A specific purpose is to elucidate how characterizations of the arrangement of matter, including rheological characterizations (e.g., texture analysis, tribology) may correlate with and/or be predictive of sensorial differences perceived by human subjects (or patients). Upon the successful completion of this research, it should be possible to predict, based upon product quality characterizations, whether test and reference products that may be compositionally different are likely to have a comparable look and feel, including comparable perceptions of grittiness, silky-smoothness, and cooling sensation.

View all Available Projects

Publications

Book Chapter

  • Mohammed, Yousuf H., Moghimi, Hamid R., Yousef, Shereen A., Chandrasekaran, Navin C., Bibi, Césa R., Sukumar, Sinduja C., Grice, Jeffrey E., Sakran, Wedad and Roberts, Michael S. (2017). Efficacy, safety and targets in topical and transdermal active and excipient delivery. Percutaneous Penetration Enhancers Drug Penetration Into/Through the Skin: Methodology and General Considerations. (pp. 369-391) Berlin, Germany: Springer Berlin Heidelberg. doi: 10.1007/978-3-662-53270-6_23

  • Grice, Jeffrey E., Moghimi, Hamid R., Ryan, Elizabeth, Zhang, Qian, Haridass, Isha, Mohammed, Yousuf and Roberts, Michael S. (2017). Non-formulation parameters that affect penetrant-skin-vehicle interactions and percutaneous absorption. Percutaneous Penetration Enhancers Drug Penetration Into/Through the Skin: Methodology and General Considerations. (pp. 45-75) Berlin, Germany: Springer Berlin Heidelberg. doi: 10.1007/978-3-662-53270-6_4

  • Leite-Silva, V. R., Grice, Jeffrey E., Mohammed, Yousuf, Moghimi, Hamid R. and Roberts, Michael S. (2017). The influence of emollients on dermal and transdermal drug delivery. Percutaneous Penetration Enhancers Drug Penetration Into/Through the Skin: Methodology and General Considerations. (pp. 77-93) Berlin, Germany: Springer. doi: 10.1007/978-3-662-53270-6_5

  • Benson, H. A. E., Mohammed, Y., Grice, J. E. and Roberts, M. S. (2016). Formulation effects on topical nanoparticle penetration. Nanoscience in dermatology. (pp. 115-126) edited by Michael R. Hamblin, Pinar Avci and Tarl W. Prow. Amsterdam, The Netherlands: Academic Press. doi: 10.1016/B978-0-12-802926-8.00009-4

  • Prow, T. W., Mohammed, Y. H., Ansaldo, A. B. and Benson, H. A. E. (2014). Topical microneedle drug delivery enhanced with magnetophoresis. Advances in dermatological sciences. (pp. 169-177) edited by Robert Chilcott and Keith R. Brain. Piccadilly, London, United Kingdom: Royal Society of Chemistry. doi: 10.1039/9781849734639-00169

Journal Article

Conference Publication

  • Roberts, Michael S., Barkauskas, Deborah, Wang, Haolu, Liu, Xin, Studier, Hauke, Pastore, Michael, Zhang, Run, Holmes, Amy, Grice, Jeffrey E., Xu, Zhiping, Mohammed, Yousuf S. and Liang, Xiaowen (2020). Multiphoton and FLIM imaging in quantifying ex vivo and in vivo body organ kinetics of solutes. Multiphoton Microscopy in the Biomedical Sciences, San Francisco, CA United States, 2-4 February 2020. Bellingham, WA United States: SPIE. doi: 10.1117/12.2546058

  • Lin, L. L., Prow, T. W., Raphael, A. P., Ansaldo, A. B., Mohammed, Y., Primiero, C. A. and Soyer, H. (2012). Microparticle and microneedle drug delivery in human skin. Conjoint 3rd Australasian Wound & Tissue Repair Society and 9th Australasian Society for Dermatology Research Conference, Sydney, NSW, Australia, 22-24 May 2012. Hoboken, NJ, United States: Wiley-Blackwell. doi: 10.1111/j.1524-475X.2012.00835.x

  • Benson, H. A. E., Mohammed, Y. H., Teixido, M. and Giralt, E. (2012). Skin penetration enhancement by cell penetrating peptides: preliminary skin permeation and efficacy assessment with diclofenac. Stratum Corneum Vll Conference 2012, Cardiff, United Kingdom, *. Chichester, West Sussex, United Kingdom: Wiley-Blackwell . doi: 10.1111/j.1468-2494.2012.00720.x

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Associate Advisor

    Other advisors:

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • This project is an exceptionally innovative combination of pharmaceutical science, materials science, nanotechnology, and clinical science to develop a state-of-the art drug delivery technology for an optimal treatment and overdose risk management of hghly potent medicinal compunds. The project will trigger a paradigm shift towards safer dosing of abuse and misuse prone drugs, which suffer from unreliable bioavailability due to solubility or permeation challenges.

  • The purpose of this project is to support the research necessary to elucidate how systematic alterations to the qualitative (Q1) and/or quantitative (Q2) composition of topical formulations impacts their physical, structural, and functional properties. A key aspect of the research relates to understanding how the thermodynamic properties of a topical dosage form change as it undergoes metamorphosis during dose application and drying on the skin, how the drug's thermodynamic activity profile during the metamorphosis of the dosage form may compare between compositionally different (non-Q1 and/or non-Q2) topical formulations, and how these and other forces may modulate the rate and extent to which topically applied drugs may become available at or near their site(s) of action in the skin. Another key aspect of the research relates to identifying and understanding other potential failure modes for bioequivalence (BE) and/or therapeutic equivalence (TE) (e.g., differences in irritation potential) that may arise between compositionally different (non-Q1 and/or non-Q2) topical formulations.

  • The purpose of this project is to support research relevant to topical semisolid drug products that will help elucidate the relationship between a product's quality attributes and its functional properties. A specific purpose is to elucidate how characterizations of the arrangement of matter, including rheological characterizations (e.g., texture analysis, tribology) may correlate with and/or be predictive of sensorial differences perceived by human subjects (or patients). Upon the successful completion of this research, it should be possible to predict, based upon product quality characterizations, whether test and reference products that may be compositionally different are likely to have a comparable look and feel, including comparable perceptions of grittiness, silky-smoothness, and cooling sensation.