Curing of aqueous polymeric film coatings: Importance of the coating level and type of plasticizer.
The aim of this study was to better understand the effects of the curing conditions on the resulting drug release patterns from pellets coated with aqueous polymer dispersions. Diltiazem HCl was used as model drug, ethylcellulose as polymer, triethyl citrate (TEC), dibutyl sebacate (DBS), and distilled acetylated monoglycerides (Myvacet) as plasticizers. Interestingly, the effects of the curing conditions strongly depended on the coating level and the type of plasticizer: in the case of TEC, the drug release rate monotonically decreased with increasing harshness of the curing conditions (time, temperature, and relative humidity), irrespective of the coating level. In contrast, in the case of DBS and Myvacet, this type of relationship was only observed at low coating levels (5%). At intermediate coating levels (around 7.5%), the curing conditions had virtually no effect on drug release. At high coating levels (10%), the release rate initially increased and then decreased with increasing harshness of the curing conditions. This more complex behavior might be attributable to the superposition of two competing phenomena: improved film formation and drug migration into the polymeric membrane. Furthermore, it could be shown that the type of plasticizer had a major effect on drug release in not fully coalesced and equilibrated film coatings, whereas the release profiles were similar for all plasticizers in the case of completely formed and equilibrated film coatings. Importantly, the latter systems were stable for long term even during storage under stress conditions.
Yang
Q W
QW
College of Pharmacy, Univ. Lille Nord de France, Lille, France.
Flament
M P
MP
Siepmann
F
F
Busignies
V
V
Leclerc
B
B
Herry
C
C
Tchoreloff
P
P
Siepmann
J
J
D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D004110:Diltiazem / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods*; D004343:Drug Implants / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D004356:Drug Storage; D045703:Emulsifying Agents / Q000737:chemistry; D006813:Humidity; D066298:In Vitro Techniques; D010968:Plasticizers / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics*; D013499:Surface Properties; D013696:Temperature; D013997:Time Factors; D017155:Wettability
D004343:Drug Implants; D045703:Emulsifying Agents; D010968:Plasticizers; D011108:Polymers; C013517:ethyl cellulose; D002482:Cellulose; D004110:Diltiazem