title: Coatless alginate pellets as sustained-release drug carrier for inflammatory bowel disease treatment.
abstract: Conventional alginate pellets underwent rapid drug dissolution and failed to exert colon targeting unless subjected to complex coating. This study designed coatless delayed-release oral colon-specific alginate pellets for ulcerative colitis treatment. Alginate pellets, formulated with water-insoluble ethylcellulose and various calcium salts, were prepared using solvent-free melt pelletization technique which prevented reaction between processing materials during agglomeration and allowed reaction to initiate only in dissolution. Combination of acid-soluble calcium carbonate and highly water-soluble calcium acetate did not impart colon-specific characteristics to pellets due to pore formation in fragmented matrices. Combination of moderately water-soluble calcium phosphate and calcium acetate delayed drug release due to rapid alginate crosslinking by soluble calcium from acetate salt followed by sustaining alginate crosslinking by calcium phosphate. The use of 1:3 ethylcellulose-to-alginate enhanced the sustained drug release attribute. The ethylcellulose was able to maintain the pellet integrity without calcium acetate. Using hydrophobic prednisolone as therapeutic, hydrophilic alginate pellets formulated with hydrophobic ethylcellulose and moderately polar calcium phosphate exhibited colon-specific in vitro drug release and in vivo anti-inflammatory action. Coatless oral colon-specific alginate pellets can be designed through optimal formulation with melt pelletization as the processing technology.
authors: Non-Destructive Biomedical and Pharmaceutical Research Centre, iPROMISE, Universiti Teknologi MARA, Puncak Alam 42300, Selangor, Malaysia; Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam 42300, Selangor, Malaysia.
authors: Siti Hajar
authors: SH
authors: Md Ramli
authors: Non-Destructive Biomedical and Pharmaceutical Research Centre, iPROMISE, Universiti Teknologi MARA, Puncak Alam 42300, Selangor, Malaysia; Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam 42300, Selangor, Malaysia. Electronic address: wongtinwui@salam.uitm.edu.my.
authors: Tin Wui
authors: TW
authors: Wong
authors: Non-Destructive Biomedical and Pharmaceutical Research Centre, iPROMISE, Universiti Teknologi MARA, Puncak Alam 42300, Selangor, Malaysia; Particle Design Research Group, Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam 42300, Selangor, Malaysia.
authors: Idanawati
authors: I
authors: Naharudin
authors: Acharya and Bm Reddy College of Pharmacy, Bangalore 107, India.
authors: Anirbandeep
authors: A
authors: Bose
mesh_terms: D000464:Alginates / Q000737:chemistry* / Q000493:pharmacokinetics*; D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics*; D065546:Drug Liberation; D005079:Excipients; D005260:Female; D005744:Gastric Acid / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D006603:Hexuronic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D057927:Hydrophobic and Hydrophilic Interactions; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013607:Tablets
chemical_list: D000464:Alginates; D002130:Calcium Phosphates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D006603:Hexuronic Acids; D013607:Tablets; D020723:Glucuronic Acid; C020243:calcium phosphate
keywords: Alginate; Melt pelletization; Pellet; Prednisolone; Ulcerative colitis