Pharmaceutical Technology: Controlled Drug Release, Volume 2

94 CH. 8] TOPICAL RELEASE AND PERMEATION STUDIES
Fig. 1—Diffusion profile of propranolol hydrochloride as a function of square root of time (t1/2) from different
polymeric matrices: ∆, Methocel ® matrix; ◊, Avicel ® CL-611 matrix; □, PVA-gelatin matrix; ○, emulsion base.
To analyse the in vitro data in terms of more meaningful parameters, the data were first treated
with a simplified Higuchi equation [22]:
(1)
where Q is the amount of drug released per unit area (cm) 2 , C 0 is the initial quantity of the drug
(mg), D is the diffusion coefficient, t is the time after application (h).
As the initial quantity of the drug (C 0 ), the diffusion coefficient (D) and π are essentially
constants, equation (1) was reduced to
(2)
The data were then treated with equation (2), and the cumulative amounts of drug released (Q)
were plotted against the square root of the time (t 1/2 ) (Fig. 1). Excellent linearity was found,
confirming that the release-permeation data followed the Higuchi model.
Since the Methocel ® matrix, formulation A, gave the maximum drug release, several additives
such as 95% ethanol, polyethylene glycol 400 and DMSO were added to it at 5%, 10% and 15%
concentration levels. Almost all additives except for ethanol at the 5% level adversely affected the
in vitro drug release (Table 3).
Furthermore, the effects of variations in polymer and drug concentration on the drug release
from formulation A were evaluated. The polymer concentration was changed from 2.0% to 1.5%
and 3.0% levels (Table 4). The change in the polymer concentration does not influence the release
of the drug. However, the variation on drug concentration in formulation A, revealed that the
propranolol hydrochloride release was directly proportional to the amount of the active drug
present. This could be attributed to the enhanced thermodynamic activity of the drug molecules in
the matrix system due to the higher concentration of the drug (Table 5 and Fig. 2).