Development of Novel Unfolding Film System of Itopride Hydrochloride Using Box-Behnken Design—A Gastro Retentive Approach

Abstract

Currently, gastro-retentive dosage forms achieved a remarkable position among the oral drug delivery systems. This is a broadly used technique to hold the drug delivery systems for a long duration in the gastro intestine (GI) region, slow drug delivery, and overcome other challenges related to typical oral delivery such as low bioavailability. The current work aimed to formulate and characterize a new expandable gastro-retentive system through Itopride Hydrochloride (IH)’s unfolding process for controlled release. The IH-loaded unfolding film formulation was optimized using the Box-Behnken design for folding endurance and length of tested layer (LTL). Initially, the formulation was made using several anti-adhesive additives to promote the unfolding mechanism. Citric acid and sodium bicarbonate were selected as anti-adhesives based on these results. The enfolded film in a capsule shell was shown to unroll in the stomach fluids and render drug delivery up to 12 h in acidic conditions. A fabricated system should have dimensions more than the size of the relaxed pyloric sphincter, and as required, >20 mm LTL was identified. This further confirms that the residence period in the stomach is irrelevant to the fed or fasted condition. Based on desirability criteria, the formulation containing 143.83, 0.7982, and 14.6096 Eudragit L100, PEG, and sodium bicarbonate are selected as optimized formulations (O-IH-UF). The optimized formulation was further analyzed for various parameters such as tensile strength, mechanical strength, unfolding nature, degradability, and in vitro release studies. The pharmacokinetic study revealed greater AUC (area under the curve) and long half-life with the designed O-IH-UF formulation, confirming that the unfolding film type can be a favorable drug system for enhancing the bioavailability of low soluble drugs. The results showed that unfolding types of gastro retentive systems could potentiate the drugs with stability issues in an alkaline medium or those with absorption in acidic conditions.

In Vitro and In Vivo Evaluation of Magnetic Floating Dosage Form by Alternating Current Biosusceptometry

“…Several types of GRDDS have been developed to increase the gastric retention time of pharmaceutical forms in the stomach, such as floating, bioadhesive, and expanding [ 12 , 13 , 14 , 15 ]. A floating drug delivery system represents a significant category of gastroretentive drug delivery mechanisms.…”

“…Several types of GRDDS have been developed to increase the gastric retention time of pharmaceutical forms in the stomach, such as floating, bioadhesive, and expanding [12][13][14][15].…”

Design and Evaluation of S-Protected Thiolated-Based Itopride Hydrochloride Polymeric Nanocrystals for Functional Dyspepsia: QbD-Driven Optimization, In Situ, In Vitro, and In Vivo Investigation

“…Functional dyspepsia, along with other gastrointestinal (GI) conditions such as upper abdominal pain, anorexia, stomach fullness, chronic gastritis, and nonulcer dyspepsia, is treated with the prokinetic medication itopride hydrochloride (ITH) [ 11 ]. The drug has a short half-life (56 h) and a small window of absorption in the stomach and upper small intestine, and these features result in its insufficient absorption and rapid clearance, and, ultimately, in its suboptimal plasma levels [ 12 , 13 ]. The intention of this study was to develop mucoadhesive NCs of ITH to increase their therapeutic efficacy because standard controlled-release formulations did not have the necessary drug release profile inside the window of absorption.…”