Regulating the release duration of probiotic targeted release tablets in the gut is crucial for ensuring optimal therapeutic efficacy. Their design must comprehensively consider the complexity of the gastrointestinal environment, the survival requirements of probiotics, and the specificity of the target site. This process is achieved through precise selection of coating materials, dynamic regulation of multilayer structures, introduction of microenvironment response mechanisms, and optimization of formulation processes, ultimately forming a complete technological chain of "anti-stress protection - targeted release - sustained action."
The selection of coating materials for probiotic targeted release tablets is the primary means of regulating release duration. Traditional formulations often use single polymer coatings, but the pH values of different segments of the gastrointestinal tract vary significantly (gastric pH 1.5-3.5, small intestine pH 6.0-7.4, colon pH 6.5-7.5), making precise control difficult with a single material. Modern technology utilizes composite coating designs, such as combining an acid-resistant layer (e.g., hydroxypropyl methylcellulose phthalate) with a pH-sensitive layer (e.g., the Eudragit series of acrylic resins), to form a gradient release structure. An acid-resistant layer protects probiotics from gastric acid inactivation, while a pH-sensitive layer dissolves only in the alkaline environment of the colon, ensuring drug release at the target site. This design not only prolongs the survival time of probiotics in the gastrointestinal tract but also avoids premature release at non-target sites.
The introduction of multi-layer coating technology for probiotic targeted release tablets further enhances the controllability of release duration. By encapsulating different functional materials layer by layer, a dual "time-space" regulatory system can be constructed. For example, the inner layer uses a rapidly dissolving material for initial release, the middle layer uses a sustained-release material to prolong the residence time in the middle segment, and the outer layer uses a colon-targeting material for precise positioning. This structure allows the release ratio of probiotics in different segments of the gastrointestinal tract to be designed as needed, such as releasing 20%-30% in the small intestine for rapid symptom relief, and the remaining portion for sustained release in the colon to maintain efficacy. The thickness of the multi-layer coating and the combination of materials need to be optimized experimentally to balance release rate and formulation stability.
The microenvironment response mechanism is a key innovation in regulating release duration. The colon's unique microbial enzymes (such as β-glucanase) and redox environment provide biomarkers for triggering release. For example, the β-glucan covalent coating technology developed by the Nanchang University team constructs a dense "armor" on the surface of probiotics through bioorthogonal chemistry. This structure remains stable in gastric acid and bile salts, but upon reaching the colon, it is gradually degraded by enzymes secreted by the intestinal flora, achieving precise release. This design not only improves the survival rate of probiotics but also extends the release duration by regulating the enzymatic hydrolysis rate, allowing the active ingredient to remain active in the colon for hours to days.
Optimization of formulation processes is crucial for the stability of release duration. Microsphere technology, by mixing drugs and excipients into tiny spheres, significantly increases the surface area to volume ratio, thereby improving release uniformity. Combined with fluidized bed coating processes, precise control of the coating thickness on the microsphere surface can be achieved, avoiding abnormal release caused by localized excessive or insufficient thickness. Furthermore, freeze-drying technology reduces microbial metabolic activity by removing moisture, extending the survival time of probiotics in the formulation and providing a basis for long-term release.
The regulation of release duration must also consider maintaining the activity of probiotics. Probiotics typically survive in the gastrointestinal tract for several days, and their numbers gradually decrease over time. Therefore, the release duration must match the probiotic's activity cycle to avoid reduced efficacy due to premature or delayed release. In vitro release experiments simulating the gastrointestinal environment (such as dynamic pH gradients and mechanical peristalsis models) can optimize formulation parameters, ensuring an optimal balance between the release amount and activity of probiotics at the target site.
Individual differences also significantly impact release duration. Dietary structure, gut microbiota composition, and disease status can all alter the gastrointestinal environment, thereby affecting the release behavior of the formulation. For example, a high-fiber diet can accelerate intestinal peristalsis, shortening the formulation's residence time in the gastrointestinal tract; while in patients with inflammatory bowel disease, intestinal pH and enzyme activity may be altered, leading to a release pattern deviating from expectations. Therefore, personalized formulation design requires preclinical studies to assess the release characteristics of different populations, employing adaptive coating materials or dosage adjustment strategies when necessary.
The regulation of release duration in probiotic targeted release tablets is a multidisciplinary field involving materials science, microbiology, and formulation engineering. Through the comprehensive application of composite coating, multilayer structures, microenvironment response mechanisms, and process optimization, precise and sustained release of probiotics in the gut can be achieved, providing reliable technical support for gut microbiota therapy. In the future, with the development of smart materials and 3D printing technology, the regulation of release duration will become even more refined, opening new pathways for personalized medicine.
