EXAMINATION OF DRUG SOLUBILITY, POLYMER TYPES, HYDRODYNAMICS AND LOADING DOSE ON DRUG-RELEASE BEHAVIOR FROM A TRIPLE-LAYER ASYMMETRIC CONFIGURATION DELIVERY SYSTEM
Lb. Yang et R. Fassihi, EXAMINATION OF DRUG SOLUBILITY, POLYMER TYPES, HYDRODYNAMICS AND LOADING DOSE ON DRUG-RELEASE BEHAVIOR FROM A TRIPLE-LAYER ASYMMETRIC CONFIGURATION DELIVERY SYSTEM, International journal of pharmaceutics, 155(2), 1997, pp. 219-229
The significance of factors such as drug solubility; polymer molecular
weight, drug loading and hydrodynamic conditions on drug release from
a swellable triple layer asymmetric configuration delivery system is
investigated. Poly(ethylene oxide) (PEG) of various molecular weights
and hydroxypropylmethyl cellulose (HPMC) were major polymeric constitu
ents of the delivery system. Theophylline, propranolol hydrochloride a
nd diltiazem hydrochloride with water solubilities of <1, 5 and > 50%,
respectively, were used as drug models. The triple-layer delivery sys
tem was produced by compressing particulate systems on a laboratory Ca
rver press with a 10-mm diameter punch and die. Results show that due
to the geometry, system design and maintenance of constant surface are
a linear release kinetics are achievable. Increase in drug solubility
expedites drug release rate and shortens duration of release; while in
crease in polymer molecular weight results in reduction of release rat
e and prolongation of release period. Drug loading does not seem to af
fect the release behavior significantly even though a freely water-sol
uble drug such as diltiazem hydrochloride was employed. In addition, w
ith an increase in stirring rate there was a corresponding increase in
release rate, while linearity of release profile remained unaltered.
Results further indicate that, as long as surface area is controlled,
front synchronization is not a prerequisite for achieving zero-order r
elease kinetics. Moreover, from a pharmaceutical perspective, the comp
lex behavior of release mechanisms for different drugs in relation to
matrix erosion, polymer swelling capacity and system design is explain
ed. (C) 1997 Elsevier Science B.V.