Drug release from pellets and matrices based on cellulose ethers.
T.his t~~sis examines the use of hydro~yprol?ylmethylcellulose (HPM~) of di.tJer~nt
VIScosities and ethylcellulose aqueous dispersion (Surelease), alone or m combination
with each other, to control the release of metoclopramide hydrochloride or diclofenac
sodium from coated pellets or matrices.
The glass transitions of the polymeric films were determined by thermomechanical
analysis and used as a guideline to select the inlet air temperature m coating operation.
The coating procedure was performed using Accela-Cota. Matrices were prepared either
by direct compression or wet granulation. Compendial dissolution methodology was used
to determine drug release from coated pellets as well as matrices. Release exponents
indicating release mechanisms were calculated from the dissolution data.
The release of both drugs from coated pellets decreased as the coating load of HPMC
increased. However HPMC did not control drug release rate and the majority of both
drugs released in less than 1 h. The release exponents for metoclopramide hydrochloride
release from HPMC E5 and HPMC E 15 coated pellets were "0.45 and .. 0.40
respectively. The corresponding value for diclofenac sodium was ..0.50. These values
of 11 indicate that diffusion is the predominant mechanism for drug release from HPMC
Cl lilted pellets.
The release of both drugs controlled with application of Surelease on drug-layered
pellets. Increasing coating load of Surelease extensively decreased the release rates of
both drugs and increased the lag times before controlled release was achieved. The
release exponent for rnetoclopramide hydrochloride was independent of coa.ting load and
the mean value was ..0.00 indicating predominantly diffusion controlled release.
However the value of n for diclofenac sodium was higher at low coating loads
suggestmg erosion controlled mechanism and decreased as the coating load increased,
indicating more diffusion controlled mechanism. The mean value was ..0.70. Inclusion
of ~PMC increased the release rates of both drugs. The Surelease:HPMC ratio had a
major role m the release rates of drugs. Addition of HPMC into Surelease did not change
the release exponent for metoclopramide hydrochloride (-0.57) from that of Surelea se
alone and diffusion remained the main mechanism controlling drug release. However the
release .exponent ("1.2X) increased for diclofenac sodium release upon addition of
HPM~ Indicating erosion controlled mechanism. Application of 2% seal-coat of HPMC
E5 pnor to Surelease resulted in decrease in the release rates of both drugs. However the
exponent n and consequently release mechanism remained unchanged for either
metoclopramide hydrochloride (,,0.00) or diclofenac sodium ( .. 0.09). Generally release
of diclofenac sodium from Surelease or SureleaselHPMC coated pellets was faster than
metoclopramide hydrochloride. This was attributed mainly to the interaction of the latter
drug with the anionic surfactant ammonium oleate present in the Surelease coat. The
interaction of metoclopramide hydrochloride with ammonium oleate was confirmed by
Drug release from HPMC matrices was controlled by the polymer content and viscosity.
The drug release was also dependent on the solubility of the drugs. Metoclopramide
hydrochloride released faster than diclofenac sodium. The release exponent for
metoclupramide hydrochloride was in the ra_nge of 0.53:0.6.4. The ~~)rre.sponding v~ue
tor diclofenuc sodium was O.59-0.XO. Therefore a combination of diffusion and erosrnn
controlled the release of either drug. The higher value of n for diclofenac sodium may
indicate the greater role for erosion than was the case for metoclopramide hydrochloride.
The incorporation of Surelease into HPMC K4M matrices considerably decreased the
release rate of metoclopramide hydrochloride while that of diclofenac sodium was less
affected. The conversion of metoclopramide hydrochloride to its base form was proposed
as an explanation. The release exponents for Surelease granulated matrices was "0.50
for both drugs indicating diffusion mainly controlled the mechanism of release.