Hydroxypropyl methylcellulose acetate succinate-based spray-dried dispersions: an overview.
Spray-dried dispersions (SDDs) of low-solubility drugs have been prepared using the polymer hydroxypropyl methylcellulose acetate succinate (HPMCAS). For a variety of drug structures, these SDDs provide supersaturation in in vitro dissolution determinations and large bioavailability increases in vivo. In bile-salt/lecithin in vitro solutions, these SDDs provide amorphous drug/polymer colloids and an increased concentration of free drug and drug in micelles relative to crystalline or amorphous drug. As dry powders, the SDDs are a single amorphous phase in which the drug remains amorphous and dispersed and does not crystallize over storage times relevant for practical drug products. A melting temperature (Tm)/glass-transition temperature (Tg) (K/K) versus log P map for 139 compounds formulated as SDDs provides a perspective on an appropriate formulation strategy for low-solubility drugs with various physical properties.
Friesen
Dwayne T
DT
Bend Research Inc., 64550 Research Road, Bend, Oregon 97701, USA. dtfriesen@bendres.com
Shanker
Ravi
R
Crew
Marshall
M
Smithey
Daniel T
DT
Curatolo
W J
WJ
Nightingale
J A S
JA
D000042:Absorption; D000284:Administration, Oral; D000336:Aerosols; D000818:Animals; D002214:Capsules; D055598:Chemical Phenomena; D003102:Colloids; D005612:Freeze Drying; D005898:Glass / Q000737:chemistry; D006801:Humans; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D013696:Temperature
D000336:Aerosols; D002214:Capsules; D003102:Colloids; D008823:Micelles; D011108:Polymers; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose