(726f) The Innovative Use of Micronized Hydroxypropyl Methylcellulose As a Pore Former in Dry Powder Coatings of Ethylcellulose Barrier Membrane Coatings on Multi-Particulates

The Innovative Use of Micronized Hydroxypropyl Methylcellulose as
a Pore Former in Dry Powder Coatings of Ethylcellulose Barrier Membrane
Coatings on Multi-Particulates

Shawn Engels^‡, Nick Grasman^†, Jason Folkenroth^† and Brian Jensen^‡

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

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

Purpose: Ethylcellulose
is commonly used throughout the pharmaceutical industry for barrier membrane
coatings for sustained drug release.  In many formulations that utilize
ethylcellulose coatings, soluble pore formers are used to modify and speed up
the release of API from the coated material.  Hydroxypropyl Methylcellulose
(HPMC) is a common pore former in these formulations that is easily blended into
traditional solution preparations of ethylcellulose and applied at precise
ratios to produce predictable, repeatable drug release.    The recent
development of a novel ethylcellulose grade for use in dry powder coatings of
multiparticulates has offered the pharmaceutical industry a vastly improved
method for applying barrier membrane coatings in a safe, fast and efficient process. 
This study investigated utilizing micronized HPMC as a dry pore former in dry
powder coatings of ethylcellulose. 

 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. Two grades of METHOCEL™
(HPMC), E3 and K3 were micronized and blended at ratios of 10%, 15% and 20%
with ETHOCEL™ HP(The
Dow Chemical Company, USA).  These blends were dry powder coated onto the APAP
beads with dibutyl sebacate (DBS) as a plasticizer using the same rotor process
as above.  Another batch was coated with 20% weight gain of ETHOCEL HP alone as
a control. Once the APAP sugar spheres were coated to 20% weight gain of ETHOCEL/METHOCEL
blends, samples were cured at a 50°C product temperature for 30 and 60 minutes
in the GXR-35. 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
the addition of the micronized METHOCEL was successful in modifying the release
of the APAP from the sugar beads.  Initial results showed that the addition
METHOCEL E3 resulted in a faster drug release than the addition of the METHOCEL
K3.  Regardless of the amount of HPMC addition to the ETHOCEL HP coating, the
process efficiency, time and yields were unaffected from the baseline process
with no addition.  No agglomeration was present in any of the trials.  Samples
have been placed on stability, and 1 month, 3 month and 6 month data will be
reported when available.    

Figure
1.
(A) Influence of the addition of various HPMC grades on APAP drug release and
(B) View of Freund-Vector GXR-35 rotor coater with powder feeder.  

Conclusion: Using the dry powder layering
process on a rotor coater allows for fast, efficient and solvent-free coatings
for ethylcellulose.  The ability to add micronized HPMC grades to the dry
powder ethylcellulose gives formulators freedom to modify the release rates
from the coatings with the same flexibility that is available with the solution
based coatings that are currently widely in use throughout the industry.  Since
the addition of the dry HPMC does not affect the coating process, the
formulation and drug release can be customized precisely without modifying the
overall coating process parameters.