Abstract
The purpose of this study is to increase the lag time and prevent release of budesonide, a corticosteroid drug used in Crohn's disease for the first 5 h and efficiently deliver it to the colon. Eudragit S100 spray-coated capsules and pulsatile systems using tablet plugs of cellulose acetate butyrate (CAB), HPMC K4M, guar gum, and pectin were prepared. Eudragit S100-coated capsules released 80.62% after 5 h. In pulsatile systems, decreasing the ratio of the polymer significantly increased the rate and extent of drug release. Spray-coating with EUD S100 decreased the extent of drug release to 48.41%, 69.94%, 80.58%, and 45.23% in CAB, HPMC K4M, pectin, and guar gum, respectively; however, the entire amount was released in the target area. In the presence of bacterial enzymes, selected formulas showed nearly 100% release. X-ray imaging performed to monitor the capsules throughout the GIT in human volunteers of the capsules and spray-coated pulsatile systems with 25% guar gum in the plug showed bursting in the transverse and ascending colon, respectively. Both formulations showed marked reduction in induced rabbit colitis model.
MeSH terms
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Administration, Oral
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Adult
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Animals
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Biological Availability
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Budesonide / administration & dosage*
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Budesonide / pharmacokinetics
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Budesonide / pharmacology
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Budesonide / therapeutic use
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Capsules
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Cellulose / analogs & derivatives
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Cellulose / chemistry
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Chemistry, Pharmaceutical / methods
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Colitis / chemically induced
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Colitis / drug therapy
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Colitis / metabolism
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Colitis / pathology
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Colon / diagnostic imaging
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Colon / drug effects
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Colon / metabolism*
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Colon / pathology
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Colon, Transverse / diagnostic imaging
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Colon, Transverse / metabolism
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Delayed-Action Preparations / chemical synthesis
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Delayed-Action Preparations / chemistry
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Delayed-Action Preparations / metabolism*
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Galactans / chemistry
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Galactans / metabolism
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Gastric Mucosa / metabolism
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Humans
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Hydrogen-Ion Concentration
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Hypromellose Derivatives
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Ileum / diagnostic imaging
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Ileum / metabolism
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Lactose / chemistry
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Male
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Mannans / chemistry
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Mannans / metabolism
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Mannosidases / metabolism
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Methylcellulose / analogs & derivatives
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Methylcellulose / chemistry
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Pectins / chemistry
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Pectins / metabolism
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Peroxidase / metabolism
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Plant Gums / chemistry
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Plant Gums / metabolism
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Polygalacturonase / metabolism
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Polymethacrylic Acids / chemistry
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Rabbits
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Radiography
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Rectum / diagnostic imaging
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Rectum / metabolism
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Stomach / diagnostic imaging
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Tablets
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Trinitrobenzenesulfonic Acid / pharmacology
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Young Adult
Substances
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Capsules
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Delayed-Action Preparations
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Galactans
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Mannans
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Plant Gums
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Polymethacrylic Acids
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Tablets
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methylmethacrylate-methacrylic acid copolymer
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Hypromellose Derivatives
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Budesonide
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ethyl cellulose
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Pectins
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Trinitrobenzenesulfonic Acid
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Cellulose
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cellulose acetate-butyrate
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Methylcellulose
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guar gum
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Peroxidase
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Mannosidases
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galactomannanase
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Polygalacturonase
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Lactose