Dear friend Amjad Ali Shah

Performing release and permeation studies of nail formulations at the normal pH of the nail, which is around 5.5, serves as a baseline reference point for several reasons:

1. Comparison to Normal Nail Conditions: By conducting studies at the normal pH of the nail, researchers establish a benchmark for evaluating the release and permeation behavior of the formulation under typical, healthy nail conditions. This allows them to assess the formulation's performance in comparison to the baseline reference.

2. Assessing Formulation Stability: Testing the release and permeation of a formulation at the normal pH helps evaluate its stability and integrity. This step ensures that the formulation remains intact and effective under standard nail pH conditions before investigating its behavior under altered or diseased pH conditions.

3. Initial Screening: Initial studies at the normal pH can serve as a screening step to determine the basic characteristics and performance of the formulation. Once the formulation demonstrates desired behavior at the normal pH, subsequent studies can explore its response under different pH conditions to mimic various stages of fungal nail infection.

4. Complexities of Higher pH Conditions: Fungal nail infections often lead to an increase in nail pH, as you rightly mentioned. Conducting studies at higher pH levels can introduce additional complexities due to changes in the nail matrix and potential interactions with the formulation. Starting with the normal pH provides a controlled environment to establish a baseline understanding before moving to more challenging conditions.

While it is important to investigate the release and permeation behavior of formulations under diseased pH conditions, it is common practice to first establish the formulation's performance at the normal pH of the nail. Once the baseline performance is determined, subsequent studies can be designed to simulate the pH changes associated with fungal nail infections, allowing for a more comprehensive assessment of the formulation's efficacy in disease-relevant conditions.

Let's keep discussing this interesting topic and exploring at your convenience.