Content area
Full text
The penetration of active substances through the skin in transdermal and topical preparations can be improved by the use of suitable penetration enhancers. Johann Wiechers of Unichema* describes how excipients can play a big role in creating a successful formulation
A good topical formulation is one that exerts the desired pharmacological activity without the occurrence of negative side-effects such as skin irritation, while being pleasant and easy to use for the patient ensuring patient compliance. A good topical formulation is therefore a lot more than just the intrinsic activity of its drug. Excipients are those chemicals in formulations that do not exert a pharmacological activity themselves, but that have an impact on many other aspects including those mentioned above. Not only do they affect the clinical effectiveness, skin irritation potential and product feel of topical formulations, but they also influence formulation structure and manufacturing. In this paper, I will primarily focus on the skin penetration enhancing aspects of excipients and provide some general recommendations of suitable skin penetration enhancers.
The importance of skin delivery
The overall pharmacological activity of a finalised formulation can be characterised by the equation:
Clinical activity of formulation = Intrinsic activity of drug V Delivery
The multiplication sign in this formula indicates that both the intrinsic activity of the drug and its delivery need to be optimised to obtain a truly active formulation. It is quite common in pharmaceutical companies to concentrate their activities in their drug design/discovery, pharmacology and toxicology departments rather than their formulation department. Once a positive pharmacological activity and toxicological profile has been established, the desire to go into clinical trials is tremendous as in vivo evidence for the clinical activity of the formulation is the ultimate goal and patents run out relatively fast. However, this approach bears the risk of failure in clinical trials. If more time and effort would be spent the selection of the proper excipients, these disappointments may be overcome.
What could excipients do to ensure that the clinical activity of the formulation is optimised? Enhancing skin delivery is useful when the concentration of drug at its site of action is below the minimal effective concentration (MEC), or if high levels of drug are needed in the formulation to reach the MEC....