Development of a Discriminating Dissolution Method for Immediate-Release Soft Gelatin Capsules Containing a BCS Class II Compound

Abstract

The purpose of this study was to develop a robust dissolution procedure for liquid-filled, soft gelatin capsules (SGCs) that can distinguish small but real changes in drug product formulation. SGCs were manufactured using different ratios of fill formulations. The formulations were evaluated by performing dissolution testing on fresh capsules and capsules that were aged at different time points and conditions. USP Apparatus 1 (basket) and 2 (paddle) at rotating speeds of 50, 75, or 100 rpm were used to evaluate the release characteristics of the formulations. The model-independent method using difference factor (f1) and similarity factor (f2) was employed to compare dissolution profiles. Dissolution data showed that fill material characteristics played a major role in controlling the rate of dissolution of our drug products. The basket increased the discriminatory power of the dissolution process regardless of speed. We observed that the paddle rotation speed may impact discrimination power but not the ability of the method to discriminate. The basket was successful for the quality assessment and characterization of formulation changes of our drug products. Through understanding of drug product characteristics and evaluating parameters of dissolution testing, a methodology can be established to enable batch-to-batch evaluation.

Challenges of Dissolution Methods Development for Soft Gelatin Capsules

“…It is important to note that the addition of surfactant to dissolution media can sometimes cause a decrease in the dissolution rates of some drug products, and in some instances can also distort drug peaks during high-performance liquid chromatography (HPLC) analysis ( Figure 7). In a previous study [63], it was found that an immediate-release SGC, containing a poorly soluble drug, loratadine, showed peaks distortion in the presence of SLS. A similar observation of a decrease in the dissolution of gelatin capsules with SLS at lower pH has also been reported by other research groups [107,108].…”

“…In previous study, it was shown that the dissolution rate obtained using the paddle method was faster, highly variable at lower time points than those obtained using the basket. In contrast, the data collected using the basket dissolution apparatus showed that the method was more selective and had less variation in terms of API release profile [63]. Table 3 shows examples of SGCs that are commercially available and their dissolution methods.…”

“…HPLC chromatograms of loratadine in 0.1 N HCl in purified water + 0.1 % SLS: (A) represents loratadine standard in 0.1N HCl, (B) loratadine soft gelatin capsule in 0.1 N HCl + 0.1% SLS dissolution media after 10 min, and (C) loratadine soft gelatin capsule in dissolution media with SLS after 60 min. Chromatographic conditions were done as described by Damian et al[63].…”

Nasal delivery of nanosuspension-based mucoadhesive formulation with improved bioavailability of loratadine: Preparation, characterization, and in vivo evaluation

“…LOR shows a poor water solubility. Thus, many studies suggested the use of 900 mL of dissolution media or/and the addition of surfactant or co-solvent in the dissolution media to fulfill sink conditions (Damian et al, 2016;Song and Shin, 2009;Vlaia et al, 2017). In this study, the sink conditions were not applied due to factors related to the limited volume of the nasal delivery, lack of surfactant on the nasal cavity to be simulated by the dissolution media and to evaluate the effect of the particle size reduction on dissolution and diffusion without any interventions from the surfactant.…”