H1: Nystatin API: Critical Quality Attributes for Antifungal Formulations

Introduction

Nystatin is a polyene antifungal drug that has stood the test of time. First discovered in the 1950s, it remains the gold standard for treating Candida infections (Thrush) in the oral cavity and gut. Because it is not absorbed significantly from the GI tract, its safety profile is excellent. However, this lack of absorption means the API's physical properties—specifically particle size and potency—are absolutely critical for its local therapeutic action.

H2: The Art of Fermentation: Streptomyces noursei

Unlike synthetic antifungals (like Fluconazole), Nystatin is a natural product of biosynthesis, produced by the fermentation of Streptomyces noursei.

• Strain Improvement: Top-tier manufacturers utilize high-yielding strains developed through classical mutation and selection. This maximizes the titer of Nystatin A1 (the active component) while suppressing related impurities.

• Downstream Processing: The extraction process must carefully separate the mycelium from the broth without degrading the fragile polyene macrolide structure. Strict temperature controls are mandated to prevent oxidation and polymerization, which darken the color and reduce potency.

H2: Micronization: The Key to Suspension Stability

Nystatin is practically insoluble in water. It is most commonly formulated as an Oral Suspension or topical cream.

• Why Micronize? To prevent the API from settling to the bottom of the bottle (sedimentation) and to ensure a smooth, non-gritty texture in the mouth, the API must be micronized.

• Specification: A typical high-grade Nystatin micronized specification requires 100% of particles to be < 45 microns, with a D50 often around 5-10 microns. This ensures the drug stays suspended longer and covers a larger surface area of the infected mucosa.

H2: Potency and Regulatory Standards

Nystatin is sold by "Units" (IU), not just weight.

• High Potency: Standard USP/EP grade requires a minimum of 4,400 IU/mg. Premium suppliers can achieve >5,500 IU/mg. Higher potency means less powder is needed per dose, allowing for cleaner formulations.

• Impurity Profile: Recent regulatory updates have tightened the limits on Impurity A, B, and C. Sourcing from a GMP-compliant facility with full documentation ensures no issues during finished product release testing.

Conclusion

Nystatin may be an "old" drug, but its manufacturing requires modern precision. For generic companies producing oral suspensions, the choice of a supplier who offers consistent micronization and high biological potency is the difference between a successful product and a recall due to sedimentation or failure of assay.