I'll share a brief story that illustrates a point about this topic. In a pharmaceutical company's Research and Development department, a formulator was assigned to develop a new Generic product, "XAPI", in tablet form. While researching existing products and the following inactive ingredients were identified:
- Lactose Monohydrate Powder
- MICROCRYSTALLINE CELLULOSE
- PVP K30
- Trisodium Phosphate Anhydrous
- Aerosil 200
- Magnesium Stearate
However, they missed one crucial step — measuring the pH of the reference listed drug (RLD).
The formulator proceeded with the preformulation studies and initiated formulation experiments, eventually stabilizing the core formula with the following components:
- Lactose Monohydrate Powder
- Avicel 102
- PVP K30
- Aerosil 200
- Magnesium Stearate
After conducting several trials, the comparative dissolution profiles and assay results confirmed that the formulation was on track. Stability study batches were then prepared and placed into stability chambers.
Upon analyzing the dissolution after three months of storage at 40°C and 75% RH, the dissolution dropped to below 70%.
A deeper review of the data revealed a critical finding: "XAPI" has polymorphic forms, with the most stable being Form 1. However, for optimal stability, the pH needs to be adjusted above 7. Further investigation revealed that the reference brand's pH was 8, whereas the developed product had a pH of 3.5. This low pH triggered the transformation from Polymorphic Form 1 to Form 2, which has a higher melting point , slower solubility and significantly reduces dissolution.
The solution was to add "Trisodium Phosphate Anhydrous" to adjust the pH and ensure the stability of the product .
This case highlights the importance of paying close attention to every small detail in product development and gathering sufficient information to proceed methodically, scientifically, and logically.
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