@jauhar123 | Posted 31 Jul. 2019
Topical formulations are becoming more popular in the pharmaceutical industry. Not only have they provided the delivery of the drug substance to a particular site, but they also avoid variations in drug levels, inter and intra-patient variations, and develop the patient’s compliance with the procedure.
In a topical formulation development, the skin functions as a perfect medium for the transfer of the drugs having both local and systemic results, but also serves a mechanical barrier for the ***** of some.
This is so because the elements in the topical applications not only react amongst themselves but also with the skin of the patient. For example, the drug substance utilized in a psoriasis treatment may be effective simply due to the hydrating or soothing results of the formulation. Whether the molecule keeps its purity, potency, and delivery to the right target site may be masked by the elements that surround it.
Both the mechanical barrier features of the top layer of skin and the physicochemical characteristics of the drug change the transportation of the drug material from the formulation to the site of action. Thus, to have the aspired benefit from topical applications, their right formulation is essential. Even a small difference in the formulation of topical drugs can make a large difference in their efficacy.
Therefore, with topical applications, the right formulation is as essential as the molecule itself to ensure that the drug substance is presented to the right target site and maintains the drug transport, dosage integrity, and active duration. Moreover, in addition to the components in the formulation, factors like pH, viscosity, and the relative amounts of oil, water, stabilizers, surfactants, droplet size, ionic nature, and the method of preparation can also affect skin absorption and efficacy.
This makes preformulation studies and careful choice of excipients highly crucial in the formulation of topical applications.
The right formulation and choice of excipients for topical application is very important as it may alter the following:
Its ability to ***** through the skin
Its stability through shelf life
It's capacity to not metabolize in skin
Its capability to stay dissolved at right concentrations
Its capability to obtain the desired release rate
Besides the excipients, care must be given to the choice of permeation enhancers in the beginning stages of topical drug development.
The bioavailability of the drug in the wanted location, i.e. the epidermis or dermis must be examined when choosing the right excipient and permeation enhancer. An excipient that forms a lot of the drug concentration in the dermis or epidermis may not be perfect for the formulation of a topical drug.
All the more, the pH of the formulations, particularly how they react to the pH factors in different layers of the skin, is very important.
Analytical method development conducted formulation, scale-up, and tech transfer performance on a molecule that was unstable, temperature-sensitive, and changed to an isomer. Initial drug charging was 97%, which fell to 50% after one month. The challenge was to discover a formulation that improved stability and maintained potency.
Because the drug substance was highly potent, deficient concentrations were needed for therapeutic effectiveness. A specific mixture of solvents/viscosity builders were required to optimize the formulation and improve scale-up.
The right formulation to topical drug development is defined by the properties of the drug substance, excipients, and the intended target area. Formulations can be developed by considering both the features of the skin and the drug substance/excipients. And all this can be examined during skin-permeation studies.