This presentation will give a brief idea about the Transdermal drug delivery system. Apart from this various physicochemical properties such as solubility, molecular weight, crystallinity, melting point that affects the TDDS has been described in brief. #ndds #tdds #nano #formulation

1. National Forensic Sciences University
Topic: Physicochemical Properties for Transdermal Drug
Delivery System
1
School of Pharmacy
Course Coordinator: Dr Deep Pooja
Presented by: Ujjwal Kumar
M Pharm (NDDS)

2. Table of Content
1. Introduction
2. Solubility (Lipophilicity)
3. Crystallinity
4. Molecular Weight
5. Melting Point
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3. Introduction
• The most common routes of drug delivery are the oral and
parenteral routes with the majority of small molecule drugs
conventionally delivered orally.
• However, most therapeutic peptides or proteins are not delivered
by the oral route, due to rapid degradation in the stomach and
size-limited transport across the epithelium.
• The primary mode of administering macromolecules is therefore
via injection which has certain limitations which is overcome by
transdermal drug delivery (TDD).
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Fig. 1 Transdermal Patch

4. 4
• TDD is a painless method of delivering drugs systemically.
• Done by applying a drug formulation onto intact and healthy skin.
• The drug initially penetrates through the stratum corneum and then passes through the
deeper epidermis and dermis.
• A large surface area of skin and ease of access allows many placement options on the skin
for transdermal absorption

5. Advantages of
TDDS
Avoids first
pass
metabolism
Constant
blood level for
longer time
Decreases
gastro-
intestinal side
effects
Increased
patient
compliance
Easy to
discontinue
Decreases the
dose of
administration
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6. 6
Disadvantages
of TDDS
TDD cannot
deliver ionic
drug
The barrier
function of
skin changes
from one site
to another
TDD cannot
achieve high
drug levels in
blood/plasma
Drugs of large
molecular size
cannot be
formulated as
TDD
Poor skin
permeability
limits the drug
delivery
Local irritation
at the site of
administration

7. Solubility
• The stratum corneum, or horny layer, is the outermost layer of the skin and has been
identified as the main barrier of the most drug permeation.
• An alternative approach is to use chemicals, known as permeation enhancers, which are
materials that can partition into, and interact with, skin constituents to induce a temporary
and reversible decrease in the skin barrier properties.
• There are a few solvents which have been used frequently in the formulation of TDDSs as
carrier and penetration enhancer, as well, such as ethanol, glycerin, propylene glycol (PG)
and polyethylene glycols (PEGs).
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8. 8
Crystallinity
• Crystallinity refers to the degree of structural order in a solid. In a crystal, the atoms
or molecules are arranged in a regular, periodic manner.
• The crystallization effect of the drug is a serious problem for the formulation design of
the transdermal patches. It makes the patches instable, reduces the amount of drug
release from the patches, and decreases the flux (the rate at which drug is entering the
skin).

9. Molecular Weight
• The transdermal route of administration cannot be employed for a large number of drugs.
• Molecules with low molecular weights easily penetrate the skin due to their small size.
• For a drug to be delivered passively via the skin it needs to have adequate lipophilicity and
also a molecular weight <500 Da.
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10. 10
Melting Point
• Molecules with high melting points, due to their low solubility both in water and fat, are
ineffective in transdermal drug delivery (TDD), and only molecules with melting points
less than 200° C were accepted.
• A method by which the melting point of a delivery system can be reduced is by eutectic
formation. A binary eutectic is a mixture of two components which do not interact to form
a new chemical compound but which, at certain ratios, inhibit the crystallization process of
one another resulting in a system with a lower melting point than either of the components.

11. References
• Chandrashekar, N. S., & Shobha Rani, R. H. (2008). Physicochemical and Pharmacokinetic
Parameters in Drug Selection and Loading for Transdermal Drug Delivery. Indian Journal
of Pharmaceutical Sciences, 70(1), 94-96. https://doi.org/10.4103/0250-474X.40340
• Suksaeree, J., Siripornpinyo, P., & Chaiprasit, S. (2017). Formulation, Characterization,
and In Vitro Evaluation of Transdermal Patches for Inhibiting Crystallization of Mefenamic
Acid. Journal of Drug Delivery, 2017. https://doi.org/10.1155/2017/7358042
• Alkilani, A. Z., McCrudden, T. C., & Donnelly, R. F. (2015). Transdermal Drug Delivery:
Innovative Pharmaceutical Developments Based on Disruption of the Barrier Properties of
the stratum corneum. Pharmaceutics, 7(4), 438-470.
https://doi.org/10.3390/pharmaceutics7040438
• Stott, P. W., Williams, A. C., & Barry, B. W. (1998). Transdermal delivery from eutectic
systems: enhanced permeation of a model drug, ibuprofen. Journal of controlled release :
official journal of the Controlled Release Society, 50(1-3), 297–308.
https://doi.org/10.1016/s0168-3659(97)00153-3
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