Stability drug substance solution

When a TLC method is validated, two of the tests that are done are (1) stability on plate and (2) stability in solution of the drug substance to determine how quickly a sample must be applied to the HPTLC plate and developed before degradation occurs, if it occurs at all. For example, five vials are prepared by placing 25 mg of drug substance in each vial, and labeling them as time 0,1,2, 3, and 4 h. The experiment begins... 

Range. Ideally, linearity should be established from 50% of the ICH reporting limit to the nominal concentration of drug substance in the sample solution (for area percent method). If the linearity does not support such a wide range of concentration, determine the linearity from 50% of the ICH reporting level to 150% of the proposed shelf life specifications of the related substance (for the high-low and external standard methods) as a minimum. This will ensure a linear response for related substances at all concentration levels to be detected during stability. 

Specificity. For HPLC analysis, resolution of the drug substance from any potential excipient and system interference peaks should be demonstrated. For a UV-Vis analysis, the absorption of the placebo solution should not be significant. It is important to note that the dissolution test is not intended to be stability indicating and will not need to be able to separate degradation peaks from the analyte peak. 

Formal Stability Studies — Long-term and accelerated (and intermediate) studies undertaken on primary or commitment batches according to a prescribed stability protocol to establish or confirm the retest period of a drug substance or the shelf life of a drug product. Impermeable Containers — Containers that provide a permanent barrier to the passage of gases or solvents (e.g., sealed aluminum tubes for semisolids, sealed glass ampoules for solutions). 

Oxidative degradation is as important as hydrolysis in the stability evaluation of new drug substances. The oxygen concentration in solution is a factor in many cases and often depends upon the solvent employed. It was reported that ascorbic acid is more stable in 90% propylene glycol or in Syrup USP than in water, presumably because of the lower oxygen concentration in these vehicles (Ravin and Radebaugh, 1990). 

It is important to characterize the physicochemical properties of the suspensions well, so that the PK data can be interpreted appropriately. Typical characterization of the drug substance includes purity, residual solvents, aqueous solubility pro Lie (pH 2, FaSSIF), crystallinity (XRPD/DSC), particle size, pl and logP. For solution formulations at various stages of discovery studies, dose analysis is essential, and for efLcacy assessment and toxicology studies, chemical stability for the... 

As part of the preformulation activities, investigations include physiochemical character, purity, solubility, stability, and optimal pH studies. In preparation for clinical studies, potential product formulations considering route of administration and solution stability are also studied. Unique to dosage form development studies for lyophilized products, thermal analysis of the drug substance and product formulations are also necessary. Data generated during this phase of product development is useful for future development activities, along with validation. 

Can API be Micronized The particle size of drug substance at the micron level is critical to achieving blending uniformity and uniformity of dosage unit.16,17 If the drug substance cannot be micronized due to physicochemical stability or material properties, consider dissolving the dmg in solution for forwarding processes. 

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