(295e) Evaluation of Static or Dynamic Curing Process for Improved Controlled Release, Dry Powder Coatings of Ethylcellulose Using a Rotor Coater

Evaluation of Static or Dynamic Curing Process for Improved
Controlled Release, Dry Powder Coatings of Ethylcellulose using a Rotor Coater

Shawn Engels^?, Cody Schoener^?, Uma Shrestha^?, Kody Bellach^?, and Brian Jensen^?

   ^?Freund-Vector Corporation, Marion, IA  52302,
USA

 ^?The Dow Chemical Company,
Midland, MI 48674 USA

Purpose: To assess how different curing
conditions influence controlled drug release from ethylcellulose, high
productivity coatings using a rotor process technology. The rotor process technology
enables the user to achieve high levels of weight gain in a short period of
time while still demonstrating sustained drug release with micronized
ethylcellulose. For this work, static and dynamic curing was assessed at
different temperatures and lengths of time to improve film coalescence to provide
more stable dosage forms. Static curing was completed in an oven while dynamic
curing was completed in the rotor coater. Optimized curing conditions and times
will enable formulators to achieve the most robust product.

Methods: Acetominophen (APAP) was dry
powder coated onto sugar spheres (#20 ? 25; Colorcon Inc., USA) using polyvinyl
pyrrolidone (K2932, ISP Inc., USA) as binder on a Granurex GXR-35 rotor process
(Freund-Vector Corp., USA). A drug to binder ratio of 97:3 w/w was maintained. Experimental
ethylcellulose samples (The Dow Chemical Company, USA) were dry powder coated
onto the APAP beads with triethyl citrate (TEC) as a plasticizer using the same
rotor process as above.  An ethylcellulose to TEC ratio of 3:1 w/w was
maintained throughout the coating. Once the APAP sugar spheres were coated to
20% weight gain of ethylcellulose, samples were either removed and static cured
or kept in the rotor coater and cured. For static curing, samples were placed
on trays and placed inside an oven for 2 hours at 60ºC. For dynamic curing, samples continued to rotate
at 250 rpm while forced, hot air was applied from above at 40 or 60ºC between 15 and 60 minutes. Dissolution and SEM were
evaluated for curing influence on drug release. USP Apparatus I (baskets) was
utilized for in-vitro dissolution studies and drug release data was compared
using similarity factor ( analysis.  

Results: Initial experiments demonstrate that
dynamic curing provided more controlled drug release compared to static curing
(Figure 1A). Dynamic curing for at 40ºC for 15 minutes was
significantly slower (by  analysis) in drug release
compared to static curing at 60ºC for 2 hours. This indicated the
combination of the force hot air plus the frictional movement caused by the
rotor bed movement enables improved film coalescence versus a static tray of
sample placed in the oven.  Dynamic curing at 40ºC for 15 minutes versus dynamic curing at 60ºC for 60 minutes was similar based on  analysis indicating a short cure time of
at least 15 minutes might provide full film coalescence and a stable coating.
Further curing assessment on drug release will be presented on samples which
were placed on stability for 1, 3, and 6 months in storage conditions of either
30ºC and 65% relative humidity or 40ºC and 75% relative humidity.

Figure
1.
(A) Influence of static vs dynamic curing on APAP drug release and (B) cross-sectional
view of rotor coater. Hot air is forced upon the product bed from above (large
arrow at top).

Conclusion: Using the rotor process and
force hot air, formulators can achieve sustained release and fully coalesced
films by dynamically curing. Dynamic curing as short as 15 minutes at 40ºC can significantly reduce curing times compared to
static curing. The combination of dynamic curing and dry powder coating using
the rotor process and micronized ethylcellulose also provides high productivity
opportunities for pharmaceutical companies when compared to traditional organic
or aqueous based ethylcellulose wurster spray coatings.