title: Factorial designed 5-fluorouracil-loaded microsponges and calcium pectinate beads plugged in hydroxypropyl methylcellulose capsules for colorectal cancer.
abstract: BACKGROUND
  The work was aimed to develop an enteric-coated hydroxypropyl methylcellulose (HPMC) capsules (ECHC) plugged with 5-fluorouracil (5-FU)-loaded microsponges in combination with calcium pectinate beads.
  
  
  METHODS
  The modified quasi-emulsion solvent diffusion method was used to prepare microsponges. A 3(2) factorial design was employed to study the formulation and the effects of independent variables (volume of organic solvent and Eudragit-RS100 content) on dependent variables (particle size, %entrapment efficiency, and %cumulative drug release). The optimized microsponge (F4) was characterized by scanning electron microscopy, powder X-ray diffraction, and thermogravimetric analysis. F4 was plugged along with the calcium pectinate beads in HPMC capsules coated with enteric polymer Eudragit-L100 (Ed-L100) and/or Eudragit-S100 (Ed-S100) in different proportions. An in vitro release study of ECHC was performed in simulated gastric fluid for 2 h, followed by simulated intestinal fluid for next 6 h and then in simulated colonic fluid (in the presence and absence of pectinase enzyme for further 16 h). The optimized formulation was subjected to in vivo roentgenographic and pharmacokinetic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon-targeted capsules.
  
  
  RESULTS
  Drug release was retarded on coating with Ed-S100 in comparison to a blend of Ed-S100:Ed-L100 coating. The percentage of 5-FU released at the end of 24 h from ECHC3 was 97.83 ± 0.12% in the presence of pectinase whereas in the control study, it was 40.08 ± 0.02%.
  
  
  CONCLUSIONS
  Thus, enteric-coated HPMC capsules plugged with 5-FU-loaded microsponges and calcium pectinate beads proved to be a promising dosage form for colon targeting.
authors.affiliation: Department of Pharmaceutics, Pranveer Singh Institute of Technology, Bhauti, Kanpur, Uttar Pradesh, India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Department of Pharmaceutics, Pranveer Singh Institute of Technology, Bhauti, Kanpur, Uttar Pradesh, India.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Tiwari
authors.affiliation: Department of Pharmaceutics, Pranveer Singh Institute of Technology, Bhauti, Kanpur, Uttar Pradesh, India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Tiwari
authors.affiliation: QA Department, Oxalis Labs, Baddi, Himachal Pradesh, India.
authors.forename: Rishabh
authors.initials: R
authors.lastname: Srivastava
keywords: In vivo roentgenograph; microsponges; numerical optimization; powder X-ray diffraction studies; thermogravimetric analysis studies