HPMC Substitution Influences the Buoyancy and Release in Gastroretentive Floating Tablets

Many compounds with high aqueous solubility, limited absorption in the upper gastrointestinal tract, poor oral bioavailability, and pH-dependent chemical stability can benefit from sustained and gastric-specific delivery systems to improve oral absorption. Intragastric floating systems represent a promising strategy to address these challenges. However, their use is limited by factors such as long floating lag time (FLT), the reliance on high viscosity hydroxypropylmethyl cellulose (HPMC), complex formulations and non-biocompatible excipients. In this study, floating tablets were developed using different grades of HPMC, sodium alginate and sodium carboxymethylcellulose and a gas generating agent. The effects of formulation variables on the in vitro drug release, floating behavior, release mechanism and physical properties were evaluated. High viscosity HPMC 2208, when used as the predominant polymer, provided sustained drug release for up to 12 h. However, it exhibited an excessively long FLT (> 6 min), increasing the risk of premature gastric expulsion which could lead to incomplete absorption and reduced therapeutic efficacy. Incorporation of HPMC 2910 and increasing its proportion within the matrix gradually reduced FLT, enabling faster buoyancy while preserving sustained release characteristics. FLT could also be optimized by fine-tuning the content of sodium bicarbonate (NaHCO₃). A higher NaHCO₃ content resulted in shorter floating lag time and shifted the release mechanism towards matrix erosion.