Combination of Pectin and Eudargit RS and Eudragit RL in the Matrix of Pellets Prepared by Extrusion-Spheronization for Possible Colonic Delivery of 5-Amino Salicylic Acid

Abstract

Background: Different methods have been studied for targeting drugs to the colon, such as pH-based, time dependent and bacterially degradable systems. However, due to variations in physiological conditions of patients, one system alone could not be completely reliable on colonic drug delivery. Objectives: The aim of this study was preparation and evaluation of a novel colon-specific drug delivery system for 5-ASA (mesalazine) pellets using pectin as a microbially degradable polymeric carrier and Eudragit RS (ERS) and Eudragit RL (ERL) as time-dependent polymers. Materials and Methods: Formulations were constructed based on a multilevel full factorial design. Pellets were prepared via extrusion -spheronization and evaluated for physicochemical properties, image analysis, SEM, FT-IR, DSC and in vitro drug release studies in the simulated gastric fluid with pH = 1.2 (SGF), simulated intestinal fluid with pH = 6.8 (SIF) and simulated colonic fluid with pH = 6.8 in presence of pectinolytic enzyme (SCF). Results: It was shown that in the presence of pectin, formulations without ERL had a relative resistance to drug release in SGF. Pellets containing pectin and the least amount of ERS had the highest burst release effect in SCF. On the other hand, increasing in amount of ERS in the formulations caused a sustained drug release. Presence of pectin in formulations containing ERS and ERL caused sensitivity of formulations to pectinolytic enzyme which can suitable for a colon specific drug delivery system. Conclusions: It was shown that combination of pectin and eudragits can relatively control drug release in the upper GI. On the other hand, pectin degraded in the presence of pectinase and formulations were susceptible to the colonic media.

Frozen in Time: Kinetically Stabilized Amorphous Solid Dispersions of Nifedipine Stable after a Quarter Century of Storage

“…To circumvent the pH-dependent effects on the drug release of the formulations, the drug release of the stored extrudates and freshly prepared samples, was studied with a dissolution experiment at constant pH of 6.8 (see Figure ). The overall dissolution behavior in this experiment still is dependent on the content of Eudragit RS as discussed above. , A propensity to lower drug release of the API with increasing content of Eudragit RS was observed. Comparing the extrudates of the distinct extrusion temperatures does not show a clear trend in dissolution behavior.…”

“…Peculiarly, not even in the currently measured dissolution profile of sample A1 this change is observed. The cause for this observation likely is the complex, pH-dependent behavior of Eudragit RS, the interplay between dissolution, and the swelling of the polymer. , A significant increase in drug release upon pH-change is not observed in the samples with higher Eudragit RS content. Taking into account the higher water content of the samples after storage, it can be speculated that the better dissolution of the well water-soluble polymer copovidone may have led to a surface diffusion effect.…”

Formulation of Indomethacin Colon Targeted Delivery Systems Using Polysaccharides as Carriers by Applying Liquisolid Technique

“…The objective of another study was to produce and evaluate a novel colon-specific drug delivery system of 5-aminosalicylic acid matrix pellets using a mixture of Eudragit RS and Eudragit RL as time-dependent polymers and pectin as a bacterially degradable polysaccharide [45]. …”

“…Therefore, a number of studies have been conducted to use a combination of polymethacrylates and polysaccharides in order to prepare more suitable dosage forms for targeting drugs to the colon [45–48]. Based on the above, each of the selected LS formulations was mixed with the appropriate amounts of E-RL 100 and lubricant and then compressed into tablets.…”

Development and Characterization of Pectin-Based Colon Targeted Pellets Containing Lactobacillus Plantarum FNCC-0461

“…The formulation variables, specifically the weight ratios of pectin in the pellet, were optimized from 5% to 20% (w/w), and their effect was observed on the shape, particle size, yield percentage, water content, and viability. The selection of a maximum concentration of 20% (w/w) was based on prior research indicating that concentrations exceeding 20% could render the formed mass extremely difficult to pelletize (Akhgari et al, 2013). The optimal process variable based on previous results was used for the preparation of uncoated pellets.…”