Gastric retentive dosage forms (GRDFs) have seen significant progress in recent years, driven by their potential to improve drug delivery and patient compliance. Some key recent developments include multi-mechanistic approaches, and magnetic systems. In multi-mechanistic approaches, a combination of different mechanisms like floating, swelling, and bio-adhesion is used to achieve more robust and consistent gastric retention, even in the fasted state. And, in magnetic systems, magnetic nanoparticles are used within the dosage form allows for external control of its movement and positioning within the stomach. This allows a more precise drug delivery.
In the last few years, advanced materials and
complicated manufacturing technology have also been applied in the GRDFs. New
polymers with tailored properties are being developed to offer improved biocompatibility,
controlled release profiles, and enhanced gastric retention capabilities. 3D
printing technology allows for the creation of complex and customized GRDFs
with precise drug distribution and release characteristics.
In clinical translation, more products are reached the
market and patient compliance is improved. Several GRDFs have been approved by
regulatory agencies in recent years, demonstrating the potential of this
technology for clinical use. In improved patient compliance, GRDFs can reduce
dosing frequency, which can improve patient adherence to treatment regimens.
Challenge: In vitro vs. in vivo performance
Accurately predicting the in vivo performance of GRDFs
based on in vitro experiments remains a significant challenge. While in vitro
tests offer valuable insights into the formulation's basic properties, the
complex and dynamic environment of the human stomach introduces several factors
not easily replicated in the lab. Here's a deeper look at the discrepancies and
ongoing efforts to bridge the gap:
Key Discrepancies:
- Dynamic vs. Static Conditions: In vitro tests typically use
static media with fixed pH and agitation, while the stomach exhibits a
dynamic environment with changing pH, viscosity, and gastric emptying
rate. This can significantly impact the performance of GRDFs, like
floating systems, whose buoyancy depends on gastric fluids.
- Fed vs. Fasted State: Most in vitro tests are
conducted in simulated fasted state conditions, but food intake
significantly alters gastric motility and fluid composition, affecting
GRDF behavior. Developing biorelevant fed-state dissolution methods is
crucial for improved prediction.
- Interindividual Variability: Stomach anatomy, physiology, and
emptying rate vary considerably between individuals, impacting GRDF
performance. In vitro models often lack this variability, potentially
leading to misleading results.
Bridging the Gap:
- Advanced In vitro Models: Researchers are developing more
sophisticated in vitro models incorporating aspects of gastric physiology,
like peristaltic movements and fed-state conditions. These models provide
a more realistic environment for evaluating GRDFs.
- Multi-method Approach: Utilizing a combination of in
vitro tests with different dissolution media, agitation conditions, and
biorelevant fed-state models can offer a more comprehensive understanding
of GRDF behavior.
- In silico Modeling: Computational simulations based
on physiological data can predict the in vivo behavior of GRDFs,
complementing in vitro experiments and informing formulation design.
Despite the challenges, researchers
are continuously advancing in vitro models and methodologies to bridge the gap
with in vivo performance. Combining these efforts within silico modeling holds
great promise for optimizing GRDF design and ultimately achieving more
predictable and effective drug delivery in the complex environment of the human
stomach.
References:
Felix Schneider, et al, In Vitro and In Vivo Test
Methods for the Evaluation of Gastroretentive Dosage Forms, Pharmaceutics. 2019
Aug; 11(8): 416.
Liza Józsa et al, Recent Options and Techniques to
Assess Improved Bioavailability: In Vitro and Ex Vivo Methods, Pharmaceutics.
2023 Apr; 15(4): 1146.
Dhaivat C Parikh et al, In vitro and in vivo techniques
to assess the performance of gastro-retentive drug delivery systems: a review,
Expert Opin Drug Deliv . 2008 Sep;5(9):951-65.
