Process Optimization for the Continuous Production of a Gastroretentive Dosage Form Based on Melt Foaming

Abstract

Several drugs have poor oral bioavailability due to low or incomplete absorption which is affected by various effects as pH, motility of GI, and enzyme activity. The gastroretentive drug delivery systems are able to deal with these problems by prolonging the gastric residence time, while increasing the therapeutic efficacy of drugs. Previously, we developed a novel technology to foam hot and molten dispersions on atmospheric pressure by a batch-type in-house apparatus. Our aim was to upgrade this technology by a new continuous lab-scale apparatus and confirm that our formulations are gastroretentive. At first, we designed and built the apparatus and continuous production was optimized using a Box–Behnken experimental design. Then, we formulated barium sulfate-loaded samples with the optimal production parameters, which was suitable for in vivo imaging analysis. In vitro study proved the low density, namely 507 mg/cm3, and the microCT record showed high porosity with 40 μm average size of bubbles in the molten suspension. The BaSO4-loaded samples showed hard structure at room temperature and during the wetting test, the complete wetting was detected after 120 min. During the in vivo study, the X-ray taken showed the retention of the formulation in the rat stomach after 2 h. We can conclude that with our device low-density floating formulations were prepared with prolonged gastric residence time. This study provides a promising platform for marketed active ingredients with low bioavailability.

In Vitro and In Vivo Studies of a Verapamil-Containing Gastroretentive Solid Foam Capsule

“…From a technological point of view, the thermal stability of verapamil is also favorable for the formulation using technology developed by our research team previously [33]. During the production of verapamil solid foam, the foam cell temperature was higher by 2 • C than that previously described with the BaSO 4 composition due to the higher melting point of the verapamil mixture [3,24]. Three compositions were produced with 15% verapamil-HCl, containing 80-120 mg of verapamil per capsule, which corresponds to the active substance content available in the literature and to the marketed preparations [20,34,35].…”

“…The foaming efficacy does not depend on only the hydrophilicity of the matrix, and according to our experiences, the particle size of the solid phase also significantly affects the degree of foaming. Previously, we successfully produced a lower-density product using smaller drug particles (314 nm ± 115) of BaSO4 with the abovementioned technology [24], and the use of verapamil particles with an average particle size (13.4 µm ± 11.2) resulted in a higher density. The drug dissolution test showed prolonged drug release in all compositions.…”

“…Three different compositions of verapamil-containing capsules (Table 1) were produced by a continuous foaming process and a device (Figure 1) that was designed and published earlier by our group [24]. For each composition, a 120.0 g molten dispersion was used for production.…”

“…The developed foaming device is suitable for the continuous production of low-density, molded, solid dosage forms that can float immediately. Due to the abovementioned properties, the foamed dosage form is a GR system, and its formation has been confirmed by in vitro and in vivo tests [3,24]. To date, we have not prepared an API-containing formulation through continuous production with the foaming device that has been subjected to in vivo pharmacokinetic testing.…”

Surface Engineering Methods for Powder Bed Printed Tablets to Optimize External Smoothness and Facilitate the Application of Different Coatings

“…As medical treatments become increasingly personalized, the preparation methods for solid dosage forms are also evolving. Over the last decade, several new oral dosage forms have gained increased attention, for example, tablets that contain APIs in a liquid state [ 1 ] and solid oral foams that increase gastroretention [ 2 , 3 ]. Another example is the application of additive manufacturing methods to produce new oral dosage forms.…”