Carboxylated high amylose starch as pharmaceutical excipients. Structural insights and formulation of pancreatic enzymes.
Carboxymethyl high amylose starch (CM-HAS) and succinate high amylose starch (S-HAS) were proposed as pharmaceutical excipients for oral drug delivery, providing a significant gastroprotection to dosage forms of pancreatic enzymes (alpha-amylase, lipase and trypsin) compared to unprotected enzymes. In acidic medium, carboxylic groups are protonated (at least in tablet surface) ensuring local buffering properties and giving a compact shape of the tablets. The enzymes were formulated individually or in association as three enzymes formulation. After the first hour of incubation (over a 2h experiment) in simulated gastric fluid (SGF), the three pancreatic enzymes retained an overall (average of the three enzymes) activity of 72% when formulated as tablets with CM-HAS excipient and 77% when formulated with S-HAS excipient. Furthermore, after incubation in SGF, the delivery of 75% of the total remaining enzymatic activity in the simulated intestinal fluid (SIF) taken 180 and 170 min for CM-HAS and S-HAS, respectively. Both formulations with carboxylated starch as excipient have a high loading capacity (up to 70-80% enzymes), which is of interest for pancreatic enzymes replacement therapy of pancreatitis. An advantage of these formulations is that gastroprotection is afforded by the carboxylated matrices (carboxylic groups), without enteric coating.
Massicotte
Louis Philippe
LP
Department of Chemistry and Centre BioMed, Université du Québec à Montréal, CP 8888, Succursale A, Montreal, Quebec H3C 3P8 Canada.
Baille
Wilms Emmanuel
WE
Mateescu
Mircea Alexandru
MA
D000688:Amylose / Q000031:analogs & derivatives* / Q000737:chemistry; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005750:Gastric Juice / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000737:chemistry*; D010195:Pancreatitis / Q000188:drug therapy; D013386:Succinates / Q000737:chemistry; D013607:Tablets; D013997:Time Factors; D014357:Trypsin / Q000737:chemistry*; D000516:alpha-Amylases / Q000737:chemistry*
D005079:Excipients; D013386:Succinates; D013607:Tablets; C027357:carboxymethylamylose; D000688:Amylose; D008049:Lipase; D000516:alpha-Amylases; D014357:Trypsin