A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media

Abstract

The aim of this study was to develop a novel microbially triggered and animal-sparing dissolution method for testing of nanorough polysaccharide-based micron granules for colonic drug delivery. In this method, probiotic cultures of bacteria present in the colonic region were prepared and added to the dissolution media and compared with the performance of conventional dissolution methodologies (such as media with rat cecal and human fecal media). In this study, the predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species, Eubacterium and Streptococcus ) were cultured in 12% w/v skimmed milk powder and 5% w/v grade “A” honey. Approximately 10 10 –10 11 colony forming units m/L of probiotic culture was added to the dissolution media to test the drug release of polysaccharide-based formulations. A USP dissolution apparatus I/II using a gradient pH dissolution method was used to evaluate drug release from formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit FS30D coated 5-fluorouracil granules was assessed under gastric and small intestine conditions within a simulated colonic environment involving fermentation testing with the probiotic culture. The results with the probiotic system were comparable to those obtained from the rat cecal and human fecal-based fermentation model, thereby suggesting that a probiotic dissolution method can be successfully applied for drug release testing of any polysaccharide-based oral formulation meant for colonic delivery. As such, this study significantly adds to the nanostructured biomaterials’ community by elucidating an easier assay for colonic drug delivery.

Novel biorelevant dissolution medium as a prognostic tool for polysaccharide-based colon-targeted drug delivery system

“…In the past 5 years, efforts have been made to develop a medium containing probiotic that can provide an effective alternative to rat cecal content. [ 13 14 15 ] The present work has established that the use probiotic containing medium may be extended to various dosage forms prepared using different polysaccharides and is not limited by the nature of formulation or types of polysaccharides used.…”

“…[ 1 ] This challenge is further intensified by the diverse strategies used in the formulation of colon-targeted delivery systems, their release being designed to be facilitated by stimuli such as pH,[ 2 3 ] pH and time,[ 2 ] presence of enzymes,[ 4 ] time,[ 6 7 8 9 ] using prodrug based,[ 7 ] pressure controlled,[ 10 ] and microbially triggered delivery systems. [ 11 12 13 14 15 16 17 18 ] The most commonly reported medium to evaluate all these types of delivery systems is the one that utilizes colon contents of rodents. [ 5 ] However, this medium has some serious limitations including lack of reproducibility, high cost, complexity of procedure, and vivisection.…”

In Vitro Methods to Study Colon Release: State of the Art and An Outlook on New Strategies for Better In-Vitro Biorelevant Release Media

“…The composition of the probiotic release media is presented in Table 4. In a similar study by Kotla et al [146], a probiotic culture was once again used to mimic the colonic environment to examine drug release from 5-fluorouracil granules coated with polysaccharides. The species used are listed in Table 4.…”

“…In this study, the drug release profiles obtained from the tests with probiotic mixture, rat caecum content and human fecal slurries were to some extent comparable. In general, the probiotic mixture resulted in a slightly faster release than the other two media [146]. Unfortunately, the choice of bacteria was not thoroughly discussed in these articles although the authors suggested that these bacteria can simulate the conditions in the colon.…”

Formulation, optimization and characterization of raloxifene hydrochloride loaded PLGA nanoparticles by using Taguchi design for breast cancer application

“…The bag remains suspended in 10 mL of dissolution media (phosphate buffer pH 6.8 by 0.5% v/v tween 80) in a beaker, employed in a rotary shaker at 37°C and rotated at 100 rpm. Aliquots of EE ( % ) = (Amount of drug in (mg) ∕ Amount of drug added (mg)) × 100 8 mL sample remain introverted at particular time intervals and substituted through fresh 8 mL of dissolution media to sustain the sink conditions (Kotla et al, 2016). The quantity of drugs released at numerous time points remains estimated through UV-Visible spectroscopy procedure.…”