Feasibility studies of concomitant administration of optimized formulation of probiotic-loaded Vancomycin hydrochloride pellets for colon delivery.
Objective of this study was to develop Vancomycin HCl pellets loaded with Saccharomyces boulardii (S.b.) for pH-dependent system and CODES™ for augmenting the efficacy of Vancomycin HCl in the treatment of colitis. Pellets were prepared by extrusion-spheronization. In the pH-dependent system, the pellets were coated with Eudragit FS 30D. These pellets exhibited spherical form and a uniform surface coating. The CODES™ system consisted of three components: core containing mannitol, drug and probiotic, an inner acid-soluble coating layer, and an outer layer of enteric coating material. Statistical factorial design was used to optimize both formulations. Scanning electron micrographs of coated pellets revealed uniform coating. In vitro drug release of these coated pellets was studied sequentially in various buffers with (2%) and without rat cecal content for a period of 12 h. From the optimized pH-dependent formulation, F6 (20% w/w coating level and 15% w/v concentration of polymer), higher amount of probiotic was released in earlier time phase (first 5 h) as compared to the CODES™ and so R5 [containing acid-soluble inner coating layer (15% w/w coating level and 12% w/v concentration of Eudragit E100), and an outer layer of enteric coating material (12% w/w coating level and 10% w/v concentration of Eudragit L100)] was considered as the best formulation after confirming in vivo X-ray studies conducted on rabbits, suggesting that Vancomycin HCl and S.b. may be co-administered as pellets [CODES™] to enhance the effectiveness of Vancomycin HCl in the treatment of colitis without its associated side effects, which can only be confirmed after clinical trials.
a Department of Pharmaceutics , Sinhgad College of Pharmacy , Pune , Maharashtra , India.
Amelia M
AM
Avachat
a Department of Pharmaceutics , Sinhgad College of Pharmacy , Pune , Maharashtra , India.
Amol S
AS
Shinde
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003092:Colitis / Q000188:drug therapy; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D005240:Feasibility Studies; D006863:Hydrogen-Ion Concentration; D008297:Male; D011109:Polymethacrylic Acids / Q000737:chemistry*; D019936:Probiotics / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011817:Rabbits; D051381:Rats; D000069983:Saccharomyces boulardii; D012995:Solubility; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D005079:Excipients; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D014640:Vancomycin
Coated pellets; Saccharomyces boulardii, Vancomycin HCl; colon delivery; extrusion–spheronization; probiotic