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Based on these results and observations, the scien- tists suspected that the low dissolution results were a product of crosslinking. Crosslinking describes the process of two or more proteins chemically joining [1, 2]. It occurs when molecules with two or more reactive sites attach themselves to specific functional groups located on the proteins, linking them together with a covalent bond. Initial testing The scientists performed dissolution testing on the product, supplying laboratory personnel with a vali- dated and replicable Phase I dissolution method with high-performance liquid chromatography (HPLC) fin- ish as detailed in Table 1. The initial dissolution test- ing of the drug product demonstrated full dissolution release at 45 minutes. Prototype stability study The scientists then placed samples of the drug prod- uct in stability chambers at ambient conditions (25°C/60 percent relative humidity [RH]) and acceler- ated conditions (40°C/75 percent RH) for a three- month prototype stability study, per US FDA and International Conference on Harmonisation guidelines for stability studies. The scientists completed a dissolution analysis of the stored capsules at the one-month time point and observed that the dissolution release for samples stored in the accelerated conditions was below the expected range. Moreover, samples stored in the accelerated conditions continued to exhibit a significantly slower dissolution release compared to the initial results at all three analysis points during the three-month proto- type stability study, with the capsules not fully dissolv- ing, as shown in Figure 1. For the samples stored in ambient conditions, on the other hand, the dissolution release showed no sig- nificant change compared to the initial data, with the capsules fully dissolving (Figure 1). Table 1 HPLC conditions Column BDS Hypersil C18, 100 × 4.6 millimeters, 3-micron particle size Profile Isocratic (50:50, acetonitrile:0.01N hydrochloric acid; mixed in-line) Flow rate 1.2 mL/min Column temperature Ambient Sample temperature 5°C Injection volume 20 microliters Detection wavelength 367 nanometers Acquisition time 8 minutes Figure 1 Dissolution data for capsules stored at ambient and accelerated conditions Percentage of capsule dissolved 120 100 80 60 40 20 0 15 30 45 60 Minutes Initial Ambient (3 months) Accelerated (3 months) Tablets & Capsules January 2019 19