Citric acid as a pH-modifying additive in an extended release pellet formulation containing a weakly basic drug

Extended release formulations aim to maintain drug solubility and release over prolonged periods. For weakly basic drugs, solubility is often pH-dependent, making pH modulation a key strategy. Prior research has shown that weak bases can precipitate in high pH environments, reducing bioavailability. This limitation has driven the search for pH-modifying excipients. However, no prior work had resolved how to maintain low pH in pellet cores consistently. The use of citric acid as a pH modifier has been explored in other contexts but not in pellet formulations. This gap motivated the investigation of citric acid as a functional core material. The goal was to determine if citric acid could maintain a low pH and control drug release. The study aimed to address the challenge of pH-dependent drug release in extended formulations.

The study aimed to develop an extended release pellet formulation for propiverine, a weakly basic drug, using citric acid as a pH-modifying core material. The objective was to evaluate how citric acid affects drug release and microenvironmental pH. The researchers wanted to compare formulations with and without pH modifiers. They also sought to assess the impact of using the free base versus the hydrochloride salt of propiverine. The motivation was to achieve controlled drug release despite pH fluctuations. The study focused on the role of citric acid in modulating pH within the pellet core. The goal was to demonstrate that citric acid could maintain a low pH and enhance drug solubility. The findings could inform the design of pH-independent extended release systems.

The study used spheronized citric acid crystals as starter cores for pellet production. These cores were coated using fluid bed coating with multiple functional layers. Different coating levels were tested to assess their impact on drug release. The formulations were compared with those using microcrystalline cellulose as starter cores. The drug was either the free base or the hydrochloride salt of propiverine. Dissolution profiles were measured over 17 hours to evaluate release behavior. The pH of the microenvironment was monitored to assess the effect of citric acid. The study focused on the interplay between pH, drug solubility, and release kinetics.

Formulations with citric acid starter cores showed controlled drug release over 17 hours. The pH modifier maintained a low pH within the pellet core, enhancing drug solubility. In contrast, microcrystalline cellulose pellets exhibited strong pH-dependent release. The free base formulation had a different release profile compared to the hydrochloride salt. The citric acid cores reduced variability in drug release caused by pH changes. The study found that citric acid effectively modulated the microenvironmental pH. Drug release was significantly slower in citric acid-based pellets compared to others. These results suggest that citric acid can be used to achieve pH-independent drug release.

The study concluded that citric acid can serve as an effective pH modifier in extended release formulations. The authors proposed that citric acid maintains a low pH in the pellet core, which enhances drug solubility. This effect was observed over a 17-hour dissolution period. The study suggested that citric acid-based formulations may reduce pH-dependent drug release variability. The authors proposed that citric acid could be used to design pH-independent extended release systems. The findings indicated that citric acid is a viable alternative to microcrystalline cellulose in this context. The study suggested that citric acid improves the reliability of drug release profiles. The authors proposed that this approach could be applied to other weakly basic drugs.