title: Drug release, preclinical and clinical pharmacokinetics relationships of alginate pellets prepared by melt technology.
abstract: BACKGROUND
  Alginate pellets prepared by the aqueous agglomeration technique experience fast drug dissolution due to the porous pre-formed calcium alginate microstructure.
  
  
  OBJECTIVE
  This study investigated in vitro drug release, preclinical and clinical pharmacokinetics relationships of intestinal-specific calcium acetate-alginate pellets against calcium-free and calcium carbonate-alginate pellets.
  
  
  METHODS
  Alginate pellets were prepared by solvent-free melt pelletization instead of aqueous agglomeration technique using chlorpheniramine maleate as model drug.
  
  
  RESULTS
  A fast in situ calcium acetate dissolution in pellets resulted in rapid pellet breakup, soluble Ca(2+) crosslinking of alginate fragments and drug dissolution retardation at pH 1.2, which were not found in other pellet types. The preclinical drug absorption rate was lower with calcium acetate loaded than calcium-free alginate pellets. In human subjects, however, the extent and the rate of drug absorption were higher from calcium acetate-loaded pellets than calcium-free alginate pellets. The fine, dispersible and weakly gastric mucoadhesive calcium alginate pellets underwent fast human gastrointestinal transit. They released the drug at a greater rate than calcium-free pellets in the intestine, thereby promoting drug bioavailability.
  
  
  CONCLUSIONS
  Calcium acetate was required as a disintegrant more than as a crosslinking agent clinically to promote pellet fragmentation, fast gastrointestinal transit and drug release in intestinal medium, and intestinal-specific drug bioavailability.
authors: a 1 Universiti Teknologi MARA , Non-Destructive Biomedical and Pharmaceutical Research Centre, iPROMISE , Puncak Alam 42300, Malaysia.|b 2 Universiti Teknologi MARA, Particle Design Research Group, Faculty of Pharmacy , Puncak Alam, 42300, Selangor, Malaysia wongtinwui@salam.uitm.edu.my.|c 3 Acharya and Bm Reddy College of Pharmacy , Bangalore 107, India.
authors: Anirbandeep
authors: A
authors: Bose
authors: a 1 Universiti Teknologi MARA , Non-Destructive Biomedical and Pharmaceutical Research Centre, iPROMISE , Puncak Alam 42300, Malaysia.|b 2 Universiti Teknologi MARA, Particle Design Research Group, Faculty of Pharmacy , Puncak Alam, 42300, Selangor, Malaysia wongtinwui@salam.uitm.edu.my.
authors: Nurulaini
authors: N
authors: Harjoh
authors: d 4 Jadavpur University, Bioequivalence Study Centre, Department of Pharmaceutical Technology , 713103, Kolkata, India.
authors: Tapan Kumar
authors: TK
authors: Pal
authors: d 4 Jadavpur University, Bioequivalence Study Centre, Department of Pharmaceutical Technology , 713103, Kolkata, India.
authors: Shubhasis
authors: S
authors: Dan
authors: a 1 Universiti Teknologi MARA , Non-Destructive Biomedical and Pharmaceutical Research Centre, iPROMISE , Puncak Alam 42300, Malaysia.|b 2 Universiti Teknologi MARA, Particle Design Research Group, Faculty of Pharmacy , Puncak Alam, 42300, Selangor, Malaysia wongtinwui@salam.uitm.edu.my.|e 5 Universiti Teknologi MARA, CoRe Pharmaceutical and Life Sciences , Shah Alam, 40450, Selangor, Malaysia.
authors: Tin Wui
authors: TW
authors: Wong
mesh_terms: D000085:Acetates / Q000737:chemistry; D000464:Alginates / Q000737:chemistry*; D002119:Calcium Carbonate / Q000737:chemistry*; D017610:Calcium Compounds / Q000737:chemistry; D002744:Chlorpheniramine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D065546:Drug Liberation; D005079:Excipients; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000085:Acetates; D000464:Alginates; D017610:Calcium Compounds; D005079:Excipients; D006603:Hexuronic Acids; D002744:Chlorpheniramine; D020723:Glucuronic Acid; D002119:Calcium Carbonate; C120662:calcium acetate
keywords: alginate; clinical pharmacokinetics; drug release; melt pelletization; pellets; preclinical pharmacokinetics