Enteric coated HPMC capsules plugged with 5-FU loaded microsponges: a potential approach for treatment of colon cancer

Abstract

The work was aimed at developing novel enteric coated HPMC capsules (ECHC) plugged with 5 Florouracil (5-FU) loaded Microsponges in combination with calcium pectinate beads. Modified quasiemulsion solvent diffusion method was used to formulate microsponges based on 3 2 factorial design and the effects of independent variables (volume of organic solvent and Eudragit RS100 content) on the dependent variables (Particle size, %EE & % CDR) were determined. The optimized microsponges (F4) were characterized by SEM, PXRD, TGA and were plugged along with calcium pectinate beads in HPMC capsules and the HPMC capsules were further coated with enteric polymer Eudragit L 100 (Ed-L100) and/ or Eudrgit S 100 (Ed-S 100) in different proportions. In vitro release study of ECHC was performed in various release media sequentially SGF for 2 h, followed by SIF for the next 6 h and then in SCF (in the presence and absence of pectinase enzyme for further 16 h). Drug release was retarded on coating with EdS-100 in comparison to blend of EdS-100: EdL-100 coating. The percentage of 5-FU released at the end of 24 h from ECHC 3 was 97.83 ± 0.12% in the presence of pectinase whereas in control study it was 40.08 ± 0.02% drug. The optimized formulation was subjected to in vivo Roentgenographic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon targeted capsules. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to 5-FU aqueous solutions. Thus, enteric coated HPMC capsules plugged with 5-FU loaded microsponges and calcium pectinate beads proved to be promising dosage form for colon targeted drug delivery to treat colorectal cancer. O trabalho teve como objetivo o desenvolvimento de novas cápsulas com revestimento entérico HPMC (ECHC) conectadas com microesponjas carregadas com fluoruracila (5-FU) em combinação com grânuos de pectinato de cálcio. O método de difusão de solvente modificado quasi-emulsão foi usado para formular microesponjas com base no planejamento fatorial 3 2 e determinaram-se os efeitos das variáveis independentes (volume de solvente orgânico e conteúdo Eudragit RS100) sobre as variáveis dependentes (tamanho de partícula, EE% e % CDR). As microesponjas otimizadas (F4) foram caracterizadas por SEM, PXRD, TGA e ligadas aos grânulos de pectinato de cálcio em cápsulas de HPMC e estas foram, ainda, revestidas com polímero entérico Eudragit L 100 (Ed-L100) e/ou Eudrgit S 100 (Ed S 100) em diferentes proporções. No estudo de liberação in vitro de ECHC foi realizada em vários meios de liberação sequencial SGF durante 2 h, seguido de SIF para as próximas 6 h, e, em seguida, em SCF (na presença e na ausência de enzima pectinase por mais 16 h). A liberação do fármaco foi retardada em revestimento com a EDS-100, em comparação com mistura de EDS-100: EDL-100, de revestimento. O percentual de 5-FU liberado de ECHC 3 ao final de 24 h foi 97,83 ± 0,12% em presença de pectinase, enquanto...

Development and In Vitro Evaluation of 5-Fluorouracil-Eluting Stents for the Treatment of Colorectal Cancer and Cancer-Related Obstruction

“…XRD patterns of pure 5FU, and PU and PU 5FU coatings were recorded ( Figure 3 ) and d -spacing values were determined for prominent peaks ( SI, Table S4 ). Pure 5FU revealed a series of characteristic diffraction peaks consistent with those reported previously [ 42 , 56 , 59 , 61 , 69 , 70 ], with a prominent 2 θ peak at 28.6° corresponding to a d -spacing of 3.123 Å. The diffractogram of the PU coating revealed a broad 2 θ peak at 19.9° and a low intensity 2 θ peak at 29.2°, which are consistent with previous literature reports and can be attributed to amorphous and semicrystalline segmented polycarbonate-PUs [ 43 , 71 , 72 ].…”

“…TGA was performed to investigate the thermal stability of 5FU within the PU matrix ( Figure 7 ). The thermogram and corresponding derivative weight loss (DTG) curve for pure 5FU implies that the onset of degradation occurs at ~200 °C with a peak maxima at ~293 °C [ 69 , 77 ]. For the PU film, the decomposition onset temperature and peak maxima were observed at ~282 °C and 335 °C, respectively [ 72 , 78 ].…”

<p>Synthesis and properties of magnetic nanotheranostics coated with polyethylene glycol/5-fluorouracil/layered double hydroxide</p>

“…For PEG polymer (Figure 8B), one main thermal event was clearly observed, occurred in the region of 170–433 °C with 97.6% weight loss 30. The TGA/DTG thermograms for 5-fluorouracil (Figure 8C) indicate a substantial mass loss of about 89.3%, displaying that the 5-fluorouracil undergoes a rapid decomposition 59…”

“…34,58 The characteristic peak of 5-FU appeared at 28.44° (Figure 1G). 59 The XRD peaks of core-shell nanoparticles with MLDH and ZLDH nanocarriers are presented in Figure 1A and B, respectively.…”

Influence of polymer ratio and surfactants on controlled drug release from cellulosic microsponges

“…Kadam et al, 2016;Zhang et al, 2016). More recently, the scope of microsponges has been extended from topical delivery to controlled release formulations intended for oral delivery (Arya and Pathak, 2014;Gupta et al, 2015a;Gupta et al, 2015b;Osmani et al, 2015;Sareen et al, 2014;Srivastava et al, 2012).…”