In Vitro and In Vivo Evaluation of Carbopol 71G NF-Based Mucoadhesive Minitablets as a Gastroretentive Dosage Form

Abstract

Gastroretentive dosage forms are intended to stay inside the stomach for a long period of time while releasing an active pharmaceutical ingredient. Such systems may offer significant benefits for numerous drugs compared to other sustained release systems, such as improved pharmacokinetics/ bioavailability and reduced intake frequency and thereby improved adherence to the medical therapy. However, there is no gastroretentive product on the market with proven reliable gastroretentive properties in humans. A major obstacle is the motility pattern of the stomach in the fasting state in humans, which reliably ensures gastric emptying of even large indigestible objects into the small intestine. One promising approach to avoid gastric emptying is adhesion of the drug delivery system to the gastric mucosa. In order to achieve mucoadhesive properties, minitablets containing Carbopol 71G NF were developed and compared to minitablets without adhesive properties. In a specialized mucoadhesive test system, the adhesion time was prolonged for adhesive minitablets (240 min) compared to non-adhesive minitablets (30 min). The in vivo transit behavior was investigated using magnetic resonance imaging in 11 healthy volunteers in fasted state in a crossover setup. It was found that the gastric residence time (GRT) of the adhesive minitablets (median of 37.5 min with IQR = 22.5−52.5) was statistically significantly prolonged compared to the non-adhesive minitablets (median of 7.5 with IQR = 7.5−22.5), indicating a delay in gastric emptying by adhesion to the gastric mucosa. However, the system needs further improvement to create a clinical benefit. Furthermore, it was observed that for 9 of 22 administrations (three minitablets were given simultaneously with every administration), the minitablets were not emptied together but showed different GRTs.

Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review

“…The use of magnetite was explored for the determination of the disintegration site and time for dosage forms, predominantly capsules. However, in several studies, ,,, problems determining exact disintegration site and time were reported due to the large size of the susceptibility feature of magnetite. This limitation was addressed by Grimm in a study where they made a clear distinction not to define a capsule rupture, but a process of “dispersion”, defined as the appearance of several small artifacts or a change in the size or the geometry of the artifact.…”

“…MRI is highly suited to imaging of the GI tract, as it can differentiate between solid and liquid components of ingested meals and intragastric gas. It has supported testing of new technologies for tailoring drug release − and allowed detailed information on drug and food interactions to be collected . Drawbacks of MRI include high instrumentation costs and unsuitability for specific patient groups, such as those with metal implants.…”

Investigation of Hydrocolloid Plant Polysaccharides as Potential Candidates to Mimic the Functions of MUC5B in Saliva

“…Currently, there is a great interest in both in vitro and ex vivo methods that allow studying mucoadhesive interactions and the delivery of drugs across both intact and diseased oral barriers [6,[59][60][61][62][63]. While several approaches have been reported, including rheological tests, ellipsometry, investigation of the wetting angle on mucin films or fixed cell layers, tensile stress tests, tack tests, AFM-spectroscopy, or the falling liquid film method, each method still has its limitations and should not be used as a stand-alone method [17,36,59,[64][65][66][67][68][69][70][71]. However, the presented in vitro tack test performed on a confluent cell layer under the consideration of oral shear stress provided in this study, can be a helpful approach in this regard.…”