Pharmaceutical Manufacturing Handbook: Production and

PHARMACEUTICAL TABLETS USING PERCOLATION THEORY 1037
60
50 y = –2.8783x + 93.63
5
40
R 4
30
3
20
10
2
1
0
0 10 20 30 40 50 60 70 80 90 100
0
0 10 20 30 40 50 60 70 80 90
% v/v HPMC % v/v HPMC
(a) (b)
2 = 0.8731
y = –0.1124x + 15.01
R2 y = –0.2704x + 7.4919
R
= 0.9903
2 = 0.8973
y = –0.0047x + 0.4418
R2 = 0.9283
25
20
15
10
5
y = –1.4671x + 39.337
R 2 = 0.8063
y = –0.0172x + 1.7095
R 2 = 0.9414
0 0 10 20 30 40 50 60 70 80 90 100
% v/v HPMC
(c)
FIGURE 41 ( a ) Higuchi slope; ( b ) normalized Higuchi slope; ( c ) relaxational constant of
Peppas and Sahlin versus percentage of excipient volumetric fraction for batch A (50 – 100 μ m
KCl and 150 – 200 μ m HPMC K4M).
6.3.9.3 Case Study: Estimation of Percolation Thresholds in Acyclovir
Hydrophilic Matrix Tablets
The principles of the percolation theory were applied to design controlled - release
matrix tablets containing acyclovir in order to estimate the percolation threshold of
the excipient in acyclovir matrix tablets and to characterize the release behavior of
these hydrophilic matrices in order to rationalize the design of these controlled -
release systems.
Acyclovir is a potent inhibitory of viruses of the herpes group, particularly herpes
simplex virus (HSV I and II) and herpes zoster varicella virus. Unfortunately, acyclovir
has a short half - life (2 – 3 h), and the oral dosage form must be taken fi ve times
daily, which is very inconvenient for patients [75, 76] . Consequently, the aim of this
study was to develop a controlled - release formulation of acyclovir that could be
taken twice daily. The materials used to prepare the tablets were acyclovir (Kern
Pharma, Tarrasa, Barcelona) and hydroxypropyl methylcellulose (Methocel K4M)
(Colorcon) a hydrophilic cellulose derivative as the matrix - forming material.
Binary mixtures were prepared with varying drug contents (60, 70, 80, 90, and
95%) keeping constant the drug and excipient particle size. Table 24 gives the composition
of the studied batches as well as the tablet thicknesses. The mixtures were
compressed on an eccentric machine (Bonals A - 300) without any further excipient.
Cylindrical tablets with a mean dosage of 500 mg and a diameter of 12 mm were
prepared at the maximum compression force accepted by the formulations.