A Micro-In-Macro Gastroretentive System for the Delivery of Narrow-Absorption Window Drugs

Abstract

A micro-in-macro gastroretentive and gastrofloatable drug delivery system (MGDDS), loaded with the model-drug ciprofloxacin, was developed in this study to address the limitations commonly experienced in narrow-absorption window (NAW) drug delivery. The MGDDS, which consists of microparticles loaded in a gastrofloatable macroparticle (gastrosphere) was designed to modify the release of ciprofloxacin, allowing for an increased drug absorption via the gastrointestinal tract. The prepared inner microparticles (1–4 µm) were formed by crosslinking chitosan (CHT) and Eudragit® RL 30D (EUD), with the outer gastrospheres prepared from alginate (ALG), pectin (PEC), poly(acrylic acid) (PAA) and poly(lactic-co-glycolic) acid (PLGA). An experimental design was utilized to optimize the prepared microparticles prior to Fourier Transition Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM) and in vitro drug release studies. Additionally, the in vivo analysis of the MGDDS, employing a Large White Pig model and molecular modeling of the ciprofloxacin-polymer interactions, were performed. The FTIR results determined that the crosslinking of the respective polymers in the microparticle and gastrosphere was achieved, with the SEM analysis detailing the size of the microparticles formed and the porous nature of the MGDDS, which is essential for drug release. The in vivo drug release analysis results further displayed a more controlled ciprofloxacin release profile over 24 h and a greater bioavailability for the MGDDS when compared to the marketed immediate-release ciprofloxacin product. Overall, the developed system successfully delivered ciprofloxacin in a control-release manner and enhanced its absorption, thereby displaying the potential of the system to be used in the delivery of other NAW drugs.

Expanding the Manufacturing Approaches for Gastroretentive Drug Delivery Systems with 3D Printing Technology

“…Single-unit floating system Layered pellets obtained in a fluidized bed processor Tablets obtained by wet granulation Tablets obtained by direct compression Tablets or capsular devices fabricated by HME/semi-solid extrusion coupled with FDM In situ gelling liquid formulation [23][24][25][26][27][28][29][30] Multiple-unit floating system Granules with APIs obtained by wet granulation Foaming encapsulated particles prepared by ultrasonic batch technology Mini-tablets with encapsulated microparticles, prepared by direct compression [23,[31][32][33][34]…”

In Vitro Effects of Waterborne Polyurethane 3D Scaffolds Containing Poly(lactic-co-glycolic acid)s of Different Lactic Acid/Glycolic Acid Ratios on the Inflammatory Response

“…Some researchers use additional chemokines [ 54 ] and immune cells [ 55 ] to reduce the inflammatory response at the implantation site, while others focus on the properties of the scaffold itself such as topology [ 56 ], modulus [ 57 ] and pore structure [ 58 ]. In addition, some segments such as PLGA are often used in tissue engineering [ 59 ]. Many researchers applied PLGA to repair bone tissue [ 60 ], osteochondral [ 61 ] and nerve tissue [ 62 ].…”