Saptarshi Kar 's page tel: +61-3-99059368 e-mail: saptarshi.kareng.monash.edu.au Room 207, Building 36 Engineering Research direction: Transdermal drug delivery - modelling and experiments

The pharmaceutical industry is probably by far one of the largest in the family of process industries. Since the dawn of modern science, pharmaceutical industries have played a major role in improving the longevity and quality of human and animal life. One of the most important features that discern pharmaceutical industries from most other process industries is the rigorous approach of quality control as humans are its largest consumers. It is rather this discerning feature that has made progress in this area a challenging task.

During the initial phase of quality control tests, the newly formulated drug compound is being administered to test animals to observe for any possible collateral damage to tissues and cells. If the drug compound in concern passes this preliminary test, the trials are then carried forward to the next stage where the bioavailability of the drug compound is being monitored, once it leaves the point of administration (oral, mucosal, nasal, rectal, ophthalmia and transdermal).

It is during this stage of trials that individuals from diverse backgrounds such as physicians, engineers, chemists, lawyers and social scientists can work together to help device proper testing strategies that are inexpensive, ethical and more or less exactly replicate the in-vivo situation the drug would encounter upon being delivered. Amongst these three criteria’s mentioned above, the first and the last are the ones where engineering expertise could be put into good use.

Over the last two decades various research groups around the globe comprising of pharmacists, physicians, engineers and chemists have been working on developing alternative approaches for testing the effectiveness of drugs upon leaving its point of administration. One such approach was to use computer simulated models that could effectively predict the pharmacodynamics of the drug once consumed by an individual. Alternative methods could involve testing in animals. However, ethical issues and dissimilarities between the metabolic rates in humans and other land dwelling animals create a lot of uncertainties. Another procedure could involve development of artificial tissues or digestive system (closely resembling in-vivo conditions) and studying the pharmacodynamic characteristics henceforth. This method though looks promising poses a lot of challenge as it is rather very difficult to physically construct artificial tissues and digestive systems closely mimicking the actual scenario.

The current project deals with one of the abovementioned testing methods. It primarily investigates the pharmacodynamics of hydrophilic drugs upon leaving its point of administration, which in our case study is the skin (transdermal). Transdermally drugs can be administered either invasively using hypodermic syringes or non-invasively either using patches (e.g. nicotine) or in the form of semi-solid cutaneous gel formulations (NSAID gels).

Though the non-invasive method of transdermal delivery seems to be the obvious method of choice, it poses its own challenge, especially while delivering high molecular weight hydrophilic drugs. This is mainly due to the fact that the outer layer of the skin (stratum corneum) is predominantly a lipid bilayer and it almost restricts any molecule to permeate through it. As such, this barrier property of stratum corneum has its own benefits as it renders protection to the underlying tissues and organs from possibly harmful exogenous matter.

Since the barrier properties of the skin restricts the permeation of drugs into the underlying vascular tissues at therapeutic rates, suitable strategies need to be designed that can enhance the permeation of the drug in concern. In the past several such enhancement techniques have been developed that either use sheer force to disrupt the lipid structure or involve modification to the drug molecule itself by attaching it to lipophilic groups that can effectively dissolve through the lipid tissues. The problem with the former technique is that its persistent use could lead to prolonged disruption of the skin structure post drug exposure period that may compromise its basic barrier functions. On the other hand attachment of lipophilic groups can lead it to permeate through the stratum corneum layer. However, if the lipophilic group does not detach thereafter, it would encounter the highly hydrous dermal layer that follows the SC and would again encounter massive permeation resistance.

It is thus imperative to device a suitable permeation enhancement strategy without compromising the barrier properties of the skin. One such strategy to do this would be to study the effect of hydration on skin structure and then subsequently investigating the drug permeation.

The preliminary part of this project deals with the study of moisture transport through the skin and its effects on the skin microstructure. Since solids (proteins and lipids) form the major constituents of the skin, the transport of moisture through the skin can be treated as a fickian diffusion problem. Though this is not in any way an exact replication of the actual transport phenomena occurring inside the skin, the diffusive term as such masks the effect of all the other transport processes into a single mathematical term called as diffusion coefficient that can be used in computer simulations. In order to remove the above uncertainties due to the masking nature of the diffusion coefficient, this parameter needs to be quantified in terms of various physicochemical properties of the skin and its surrounding environment. The numerical simulations involving moisture transport will also take into account the effect of structural alterations in the skin since it is known that hydration creates increase in the thickness of skin layers.

Once the physics behind moisture transport through skin is well understood, a few hydrophilic drug formulations will be tested for their permeability through skin layer at various degrees of skin hydration. Furthermore, detailed math models pertaining to the interactive effect between the drug, water molecule and skin structure will also be developed.

Personal Intersets:

Music:Pink floyd, Phil Collins, George Michael, Francis Lai, Kenny Gorlick (G), Eric Clapton etc.
I am also a big fan of cricket and have always gone out of my way collecting statistics.
X files, yes this is something that has always fascinated me and I am on my way piling up my DVD collections for all the seasons.Incidentally its not Mulder and Scully who are my favouraite characters but rather I liked the roles of Deep Throat, Mr X and of course the Cancer Man.

Publications:

1)Kar. S and Chen. X.D. Effect of high mass fluxes on heat and mass transfer through a flat surface. Transactions IMechE (Part E) 218(2004): 213-220.
2)Kar.S, Chen. X.D and Nelson. M.I. Direct-contact Heat Transfer Coefficient for Condensing Vapor Bubble in Stagnant Liquid Pool. Chemical Engineering Research and Design (Trans IChemE Part A) 2006, Accepted for publication.
3)Kar. S, Chen. X.D, Adhikari. B.P, Hossain. M.M and Garg. S. Estimation of moisture diffusivity of porcine skin. Proceedings Chemeca 2006, Auckland, New Zealand, Sep-2006.

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