Spray-dried high-amylose sodium carboxymethyl starch: impact of α-amylase on drug-release profile.
Spray-dried high-amylose sodium carboxymethyl starch (SD HASCA) is a promising pharmaceutical excipient for sustained-release (SR) matrix tablets produced by direct compression. The presence of α-amylase in the gastrointestinal tract and the variations of the gastric residence time of non-disintegrating dosage forms may affect the presystemic metabolism of this excipient and, consequently, the drug-release profile from formulations produced with SD HASCA. In this study, the influence of α-amylase and the residence time in acidic conditions on the drug-release profile was evaluated for a once-daily acetaminophen formulation (Acetaminophen SR) and a once-daily tramadol hydrochloride formulation (Tramadol SR). Both formulations were based on SD HASCA. α-Amylase concentrations ranging from 0 IU/L to 20000 IU/L did not significantly affect the drug-release profiles of acetaminophen and tramadol hydrochloride from SD HASCA tablets (f2 > 50) for all but only one of the studied conditions (f2 = 47). Moreover, the drug-release properties from both SD HASCA formulations were not significantly different when the residence time in acidic medium was 1 h or 3 h. An increase in α-amylase concentration led to an increase in the importance of polymer erosion as the main mechanism of drug-release instead of drug diffusion, for both formulations and both residence times, even if release profiles remained comparable. As such, it is expected that α-amylase concentration and residence time in the stomach will not clinically affect the performance of both SD HASCA SR formulations, even if the mechanism of release itself may be affected.
a Faculté de pharmacie, Université de Montréal , Montreal , Quebec , Canada.
Teresa
T
Nabais
a Faculté de pharmacie, Université de Montréal , Montreal , Quebec , Canada.
Sarra
S
Zaraa
a Faculté de pharmacie, Université de Montréal , Montreal , Quebec , Canada.
Grégoire
G
Leclair
D000082:Acetaminophen / Q000008:administration & dosage / Q000737:chemistry*; D000688:Amylose / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D013213:Starch / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D013607:Tablets / Q000737:chemistry* / Q000493:pharmacokinetics; D013997:Time Factors; D000516:alpha-Amylases / Q000737:chemistry* / Q000493:pharmacokinetics
D004337:Drug Carriers; D005079:Excipients; D013607:Tablets; D000082:Acetaminophen; D013213:Starch; D000688:Amylose; C034848:carboxymethyl starch; D000516:alpha-Amylases
drug delivery; drug diffusion; hydrophilic matrices; in vitro drug-release; modified starch; polymer erosion; spray drying; sustained-release; α-amylase