TY - JOUR

T1 - The effect of surfactants on the dissolution behavior of amorphous formulations

AU - Mah, Pei T

AU - Peltonen, Leena

AU - Novakovic, Dunja

AU - Rades, Thomas

AU - Strachan, Clare J

AU - Laaksonen, Timo

N1 - Copyright © 2016 Elsevier B.V. All rights reserved.

PY - 2016/6

Y1 - 2016/6

N2 - The optimal design of oral amorphous formulations benefits from the use of excipients to maintain drug supersaturation and thus ensures adequate absorption during intestinal transit. The use of surfactants for the maintenance of supersaturation in amorphous formulations has not been investigated in detail. The main aim of this study was to investigate the effect of surfactant on the dissolution behavior of neat amorphous drug and binary polymer based solid dispersion. Indomethacin was used as the model drug and the surfactants studied were polysorbate 80 and poloxamer 407. The presence of surfactants (alone or in combination with polymers) in the buffer was detrimental to the dissolution of neat amorphous indomethacin, suggesting that the surfactants promoted the crystallization of neat amorphous indomethacin. In contrast, the presence of surfactants (0.01% w/v) in the buffer resulted in a significant improvement on the dissolution behavior of binary polymer based solid dispersion. Incorporating the surfactant to the formulation to form ternary solid dispersion adversely affected the dissolution behavior. In conclusion, the use of surfactants (as wetting or solubilization agents) in dissolution studies of neat amorphous drugs requires prudent consideration. The design of amorphous formulations with optimal dissolution performance requires the appropriate selection of a combination of excipients and consideration of the method of introducing the excipients.

AB - The optimal design of oral amorphous formulations benefits from the use of excipients to maintain drug supersaturation and thus ensures adequate absorption during intestinal transit. The use of surfactants for the maintenance of supersaturation in amorphous formulations has not been investigated in detail. The main aim of this study was to investigate the effect of surfactant on the dissolution behavior of neat amorphous drug and binary polymer based solid dispersion. Indomethacin was used as the model drug and the surfactants studied were polysorbate 80 and poloxamer 407. The presence of surfactants (alone or in combination with polymers) in the buffer was detrimental to the dissolution of neat amorphous indomethacin, suggesting that the surfactants promoted the crystallization of neat amorphous indomethacin. In contrast, the presence of surfactants (0.01% w/v) in the buffer resulted in a significant improvement on the dissolution behavior of binary polymer based solid dispersion. Incorporating the surfactant to the formulation to form ternary solid dispersion adversely affected the dissolution behavior. In conclusion, the use of surfactants (as wetting or solubilization agents) in dissolution studies of neat amorphous drugs requires prudent consideration. The design of amorphous formulations with optimal dissolution performance requires the appropriate selection of a combination of excipients and consideration of the method of introducing the excipients.

KW - Journal Article

U2 - 10.1016/j.ejpb.2016.03.007

DO - 10.1016/j.ejpb.2016.03.007

M3 - Journal article

C2 - 26955750

VL - 103

SP - 13

EP - 22

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

ER -