<p>Enhancement of Oral Bioavailability of Ibandronate Through Gastroretentive Raft Forming Drug Delivery System: In Vitro and In Vivo Evaluation</p>

Abstract

Background: Bisphosphonates have very low bioavailability and cause irritation of the esophagus and stomach. This study was planned to improve the oral bioavailability of ibandronate through the formation of a raft in the stomach. Bisphosphonate-induced irritation of the esophagus and stomach is prevented by the formation of a raft. Materials and Methods: The nanostructured raft was developed through the use of nanosized citrus pectin (NCP). The particle size of NCP was measured by zeta sizer and SEM. The percentage of NCP and the neutralization profile of raft was studied. The ibandronate, polymers, and the developed formulation were characterized by FTIR, XRD, TGA, and DSC. The release of ibandronate was studied in 0.1 N HCl, 0.5 N HCl, 1 N HCl, and simulated gastric fluid (SGF) and a cell viability study was performed using Caco-2 cells. The PPR5 formulation and Bonish 150 mg tablets were selected as test and reference formulations, respectively, for pharmacokinetic study. Twelve healthy albino rats were taken and divided into two groups using a Latin square crossover design, and the blood samples were collected for 24 hours. Results: The SEM image showed that the particle size of NCP was 159 nm. The raft of PPR5 showed 94% NCP and 45 minutes duration of neutralization. The FTIR and XRD showed chemical stability and a uniform distribution of ibandronate in the raft. The TGA and DSC indicated the thermal stability of formulation. The release of 99.87% ibandronate at 20 minutes was observed in the SGF. The values of C max for the reference and test formulations were 493±0.237 ng/mL and 653±0.097 ng/mL, respectively. The AUC (0-t) of the reference and test formulations was 3708.25±3.418 ng/mL.h and 6899.25±3.467 ng/mL.h, respectively. Conclusion: The NCP has been successfully prepared from citrus pectin and has shown effective porous raft formation. The bioavailability of the ibandronate from newly developed PPR5 was higher than the already marketed formulation.

Gastroretentive Technologies in Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug Bioavailability and Patient Compliance Implications

“…The tablets demonstrated a rapid release of ibandronate that was completed within 20 min, potentially due to rapid diffusion of the drug through the foam structure of the raft that was ought to the incorporation of NCP into the formulation. Furthermore, an in vivo study in albino rats demonstrated an enhanced bioavailability of ibandronate in the rats, compared to a reference formulation, potentially due to the effective penetration enhancement of PEG 400 [124].…”

“…While liquid is the most common formulation form for raft-forming systems, recently, Hanif et al reported the development of gastroretentive raft-forming tablets containing ibandronate. Nanosized citrus pectin (NCP) was prepared and used as the raft-forming polymer in the tablets, due to its gelling, antacid and antiulcer properties [124]. When combined with calcium carbonate, NCP demonstrated the highest gel strength, due to a cross-linking pattern of the raft through the calcium ions [125].…”

Physicochemical properties of various alginate-based raft-forming antacid products: a comparative study

“…Rafts were formed in SGF (150 ml, equilibrated to 37ºC in a water bath for 20 mins), by adding the maximum recommended dose of the product using a syringe. The formed rafts were allowed to mature in a water bath (37°C for 30 mins) and used to assess the following neutralization parameters: 6,20…”

“…This was repeated consecutively until the pH of the filtrate was no longer neutralized by the raft (pH <4 or pH ≤the previous reading). 6,20 These rafts were used for studying the effect of raft structure.…”

Designing and Development of Gastroretentive Mucoadhesive Microspheres of Cefixime Trihydrate Using Spray Dryer

“…This increase in drug residence time in the stomach increases bioavailability, reduces wastage of the drug, and enhances the solubility of the drug, which is less soluble in the gastric environment. The mucoadhesive polymers are used to increase drug retention and improve the oral bioavailability of drugs due to close contact with the gastric mucus layer; this interaction of the bio-adhesive polymer with the mucus layer of a mucus membrane is known as mucoadhesion [5][6][7][8][9][10].…”