Journal of Controlled Release 94 (2004) 313 – 321

www.elsevier.com/locate/jconrel

Improvement in the disintegration of shellac-coated soft gelatin

capsules in simulated intestinal fluid
Nantharat Pearnchob, Andrei Dashevsky, Roland Bodmeier *
College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany

Received 7 April 2003; accepted 8 October 2003

Abstract

Shellac is a natural enteric polymer, which results in good gastric resistance; however, it often dissolves too slowly in
intestinal fluids. The objective of this study was to improve the disintegration of shellac-coated soft gelatin capsules in
simulated intestinal fluids (phosphate buffer pH 6.8) through the addition of pore-formers, such as organic acids and hydrophilic
polymers, while retaining gastric resistance. The mechanical properties (% elongation at rupture, puncture strength at break and
modulus at puncture), media uptake and weight loss of shellac films were determined upon exposure in 0.1 N HCl and/or
phosphate buffer pH 6.8. Organic acids (e.g., sorbic acid) acted as plasticizers, they reduced the glass transition temperature of
ethanol-cast shellac films. The addition of additives effectively decreased the disintegration times in phosphate buffer pH 6.8,
while the behavior in 0.1 N HCl remained unchanged. In addition, the hardness and disintegration of shellac-coated soft gelatin
capsules were monitored through the whole disintegration experiments. The best disintegration was achieved with sorbic acid as
pore-former. Sorbic acid remained in the shellac coating at low pH, but leached in pH 6.8 buffer, thus resulting in good gastric
resistance and rapid disintegration in simulated intestinal fluids. The disintegration time of ethanolic shellac-coated soft gelatin
capsules decreased with increasing amount of pore-former. The slow disintegration of aqueous shellac-coated soft gelatin
capsules could be also improved by the addition of hydrophilic polymers, such as hydroxypropyl methylcellulose (HPMC).
However, higher HPMC concentrations were required when compared to sorbic acid.
D 2003 Elsevier B.V. All rights reserved.

Keywords: Capsules; Coating; Enteric polymers; Plasticizers; Pore-former; Shellac

1. Introduction polymers of synthetic or natural origin are commer-

cially available. The synthetic polymers are primarily
Enteric polymers carry acidic functional groups either cellulose-derived, such as cellulose acetate
and have a pH-dependent solubility; they are insoluble phthalate, hydroxypropyl methylcellulose acetate suc-
at low pH (e.g., gastric fluids) and dissolve in higher cinate, hydroxypropyl methylcellulose phthalate or
pH media (e.g., intestinal fluids) [1,2]. Various enteric acrylate-based such as EudragitR L and EudragitR S
[1,3 – 5]. These polymers dissolve rapidly at pH values
between 5 and 7.
* Corresponding author. Tel.: +49-30-83850643; fax: +49-30-
Shellac is the natural enteric material of choice,
83850692. which is derived from the hardened secretion of the
E-mail address: bodmeier@zedat.fu-berlin.de (R. Bodmeier). insect Kerria lacca [1– 4,6,7]. Because of its natural

0168-3659/$ - see front matter D 2003 Elsevier B.V. All rights reserved.
doi:10.1016/j.jconrel.2003.10.004
314 N. Pearnchob et al. / Journal of Controlled Release 94 (2004) 313–321

origin, shellac is an acceptable enteric coating mate- 2.3. Preparation of shellac solutions
rial for phytopharmaceuticals and food additives,
where synthetic polymers do not fit into the product A 10% (w/v) ethanolic shellac solution was
image [8]. Shellac is brittle in nature and therefore prepared by dissolving shellac in ethanol. Shellac
does not have good film-forming properties. The was added to an aqueous ammonium hydroxide
addition of a plasticizer, such as triethyl citrate (15% v/v) solution to prepare a 10% w/v aqueous
(TEC), significantly improves the mechanical prop- solution with a degree of neutralization of 0.8. The
erties of shellac films [9,10]. Shellac has good shellac suspension was agitated and heated (50 – 60
resistance in gastric fluids, but a major problem is jC) until a clear solution with a pH 7 – 8 was
the slow dissolution of shellac coatings in higher pH obtained. The plasticizer (triethyl citrate) and/or
media, such as intestinal fluids. This can be attrib- hydrophilic additive (% w/w, based on the polymer)
uted to its relatively high apparent pKa of between was added after dissolution of the shellac. This
6.9 and 7.5 [11 –13]. solution was further stirred at room temperature for
The objective of this study was to improve the 30 min in the case of the ethanolic solution or for 24
disintegration behavior of shellac-coated capsules in h in the case of the aqueous solution.
simulated intestinal fluid (pH 6.8 buffer), while
retaining good resistance in simulated gastric fluid 2.4. Preparation of polymeric films
(0.1 N HCl). The approach to achieve this objective
was the incorporation of hydrophilic additives in the Polymeric films (thickness 100 – 300 Am) were
shellac coating. prepared by casting a 10% (w/v) ethanolic solution
or a 10% w/v aqueous polymer solution onto Teflon
frames mounted on leveled glass plates (area of
2. Materials and methods casting, 14  14 cm2). The polymer solutions were
dried into films at room temperature (ethanolic poly-
2.1. Materials mer solutions) or in an oven at 50 jC (aqueous
polymer solutions) for 48 h. The dried films were
Shellac (decolorized and dewaxed grade, SSBR then peeled from the Teflon plate and cut into pieces
55 Pharma) (donated by Stroever Schellack Bremen, of 4  4 cm2. For the preparation of wet films, the dry
Bremen, Germany), hydroxypropyl methylcellulose films were placed in perforated bags (7  7 cm2, made
(HPMC; MethocelR E5, donated by Colorcon, Or- from a 40-mesh plastic screen) to avoid sticking and
pington, UK), Triethyl citrate (TEC) (donated by folding of the films during exposure to the dissolution
Morflex, Greensboro, NC, USA), adipic acid, medium. The samples were placed in 0.1 N HCl and
alginic acid, benzoic acid, citric acid, fumaric acid, shaken in a horizontal shaker at 37 jC and 80 rpm for
sorbic acid (purchased from Sigma, St. Louis, MO, 120 min (GFLR 3033, Gesellschaft für Labortechnik,
USA), gelatin type B bloom strength 75 (donated Burgwedel, Germany).
by Sanofi Bio-Industries, Angoulème, France), 25%
ammonium hydroxide (purchased from Merck, 2.5. Mechanical properties of shellac films
Darmstadt, Germany), ethanol (reagent grade) and
oil-filled oblong soft gelatin capsules (donated by The mechanical properties of the films in the dry
R.P. Scherer, Eberbach, Germany). and wet states were measured by a puncture test
with an InstronR 4466 mechanical testing device
2.2. Solubility of organic acids (Instron Wolpert, Ludwigshafen, Germany) using a
metal probe with a hemispherical end (diameter, 5
The solubility of the various organic acids in mm; length, 50 mm). The load at break and the
different dissolution media (0.1 N HCl or phosphate maximum displacement of the film samples were
buffer pH 6.8, room temperature) was determined by determined and then converted to the puncture
adding increasing amounts of organic acid to the strength (MPa), elongation at puncture (%) and
media until no more acid could be dissolved. modulus at puncture (kPa). A detailed description
 N. Pearnchob et al. / Journal of Controlled Release 94 (2004) 313–321 315

of the puncture test has been published previously pneumatic spraying pressure, 1.2 bar; spray rate, 5 –7
[14,15]. g/min; spray nozzle diameter, 1.2 mm; pan rotation
speed, 15 rpm.
2.6. Water uptake and weight loss of shellac films
2.9. Disintegration of shellac-coated soft gelatin
The water uptake and the weight loss of shellac capsules
films were measured upon exposure to 0.1 N HCl or
phosphate buffer pH 6.8 in a horizontal shaker (GFLR Disintegration testing of soft gelatin capsules was
3033; 37 jC, 80 rpm, 120 min, n = 3). The film samples carried out according to pharmacopoeial requirements
were removed from the medium at predetermined time (900 ml, 0.1 N HCl or phosphate buffer pH 6.8, 37
intervals and carefully blotted with tissue paper to jC) (ErwekaR disintegration tester ZT24, Erweka,
remove the water on the film surface and then weighed Heusenstamm, Germany). Six capsules of each batch
to measure the weight change due to water uptake and were placed for 120 min into 0.1 N HCl, and then into
leaching of the polymer and/or additive. The water phosphate buffer pH 6.8.
uptake of the polymeric films was calculated as fol-
lows: % water uptake=[(Wt Wd)/Wt]  100, where Wt 2.10. Hardness of shellac-coated soft gelatin capsules
is the weight of the wet film at time t, Wd is the weight
of the wet film, which was removed from the dissolu- The hardness of coated soft gelatin capsules in dry
tion medium at time t and oven-dried at 50 jC for 48 h. and wet states were determined with an InstronR
The % weight loss and % dry weight were calculated as 4466. Wet capsules were obtained by exposing coated
follows: % weight loss=[(Wo Wd)/Wd]  100, where soft gelatin capsules to 0.1 N HCl for 120 min,
Wo is the original weight of the dry film; % dry followed by 10 and 30 min in phosphate buffer pH
weight = 100% [(Wo Wd)/Wd]  100. 6.8 in a horizontal shaker (37 jC, 80 rpm, n = 10)
(GFLR 3033). The probe was forced downwards onto
2.7. Thermal analysis of shellac films the sample at a constant speed of 10 mm/min and the
resulting force was monitored. The load at break (N)
Thermograms of unplasticized and plasticized shel- was measured.
lac films were obtained by using a differential scan-
ning calorimeter (Mettler Toledo DSC821e ) and
STARR software (Mettler Toledo, Giessen, Germany) 3. Results and discussion
to determine the glass transition temperature (Tg). The
temperature calibration was accomplished with the The objective of this study was to accelerate the
melting transition of indium. The samples (7 – 10 disintegration of shellac films in simulated intestinal
mg), which were stored in a vacuum desiccator prior fluid, while retaining good resistance in simulated
to analysis, were sealed in aluminum pans. All tests gastric fluid. Low molecular weight organic acids,
were run under a nitrogen atmosphere at a scanning which should promote the disintegration/dissolution
rate of 10 jC/min. of shellac at higher pH values, were added to the
shellac film.
2.8. Coating of soft gelatin capsules The visual appearance and flexibility of organic
acid-containing shellac films prepared by ethanolic
Soft gelatin capsules were coated in a pan-coater film-casting is given in Table 1. In most cases, the
(GlattR GC-300, Glatt, Binzen, Germany) with a 10% organic acid-containing films were clear except for
(w/v) ethanolic solution or a 10% (w/v) ammoniated the fumaric acid-containing films. At higher acid
aqueous solution of shellac and additives. The coating concentrations ([10% (w/w)), crystals appeared
conditions were: batch size, 1.2 kg; prewarming of the within the clear films. Fumaric acid was only
capsules at 30 jC for 30 min before coating; product slightly soluble in ethanolic shellac solution (9.8 g
temperature, 20 – 25 jC (ethanolic solution) and 38– in 100 g 95% v/v aq. ethanol at 30 jC) [16] and
42 jC (aqueous solution); air flow rate, 130 m3/h; was therefore dispersed in the shellac solution and
316 N. Pearnchob et al. / Journal of Controlled Release 94 (2004) 313–321

Table 1
Physical properties of organic acids
Organic acid, Molecular Solubility, mg/ml Shellac films
% w/w based weight 0.1 N HCl pH 6.8 Appearance Flexibility
on polymer
None clear very brittle
Sorbic acid 112.13 1–2 15 – 16
5 clear flexible
10 clear with crystals very flexible
20 clear with crystals very flexible
Benzoic acid 122.12 3–4 22 – 23
5 clear brittle
10 clear with crystals flexible
20 clear with crystals flexible
Fumaric acid 116.07 4–5 20 – 21
5 cloudy and crystals flexible
10 cloudy and crystals flexible
20 cloudy and crystals flexible
Adipic acid 146.14 24 – 25 48 – 49
5 clear flexible
10 clear with crystals very flexible
20 clear with crystals very flexible
Citric acid 192.13 >1000 >1000
5 clear very brittle
10 clear with crystals very brittle
20 clear with crystals very brittle
Visual appearance and flexibility of organic acid-containing shellac films prepared by ethanolic film casting.

resulted in cloudy films with dispersed acid par- out acid) to 36 – 64% (with acid). The puncture
ticles. Pure shellac films were brittle. Except for strength of the films was similar; the modulus at
citric acid at all investigated levels and benzoic acid puncture of acid-plasticized films was consequently
at 5% (w/w), the addition of organic acids resulted lower than that of pure films. As a result, the
in flexible films, which is advantageous with regard organic acids improved the flexibility of ethanol-
to the mechanical stability of the shellac films cast shellac films.
during coating and further processing. The investi- The effectiveness of plasticizers can be character-
gated acids apparently acted as a plasticizer for ized by the glass transition temperature, Tg [17,18].
shellac. The mechanical properties of shellac films The organic acids were more efficient plasticizers for
were measured with a puncture test (Table 2). The shellac when compared to the commonly used plasti-
addition of 5% w/w acids resulted in an increase in cizer, TEC (Table 3). With an acid concentration of
the elongation of the shellac films from 1% (with- only 5% (w/w), the Tg of shellac films was signifi-
cantly lowered from approx. 40 to 11 –15 jC. The
effectiveness of the organic acids and TEC as plasti-
Table 2
cizer can be ranked as follows: adipic acid, benzoic
Mechanical properties of ethanol-cast shellac films containing 5%
(w/w) organic acids (mean value F standard deviation) acid>sorbic acid>TEC.
Organic acid Elongation, Puncture Modulus at
The results of water uptake and weight loss studies
% strength, puncture, kPa of ethanol-cast shellac films containing different
MPa amounts of sorbic acid or TEC, after immersion for 2
None 1.0 (0.1) 1.7 (0.7) 67.5 (43.6) h in 0.1 N HCl or phosphate buffer pH 6.8, are shown
Sorbic acid 35.6 (2.5) 1.9 (2.8) 53.3 (1.8) in Fig. 1. After immersion in 0.1 N HCl, the shellac
Benzoic acid 52.0 (9.3) 1.7 (0.1) 22.7 (0.7) films (with or without additive) kept their weight (Fig.
Adipic acid 64.4 (5.2) 1.6 (0.3) 12.1 (0.8) 1A) and remained clear, indicating a low water content
 N. Pearnchob et al. / Journal of Controlled Release 94 (2004) 313–321 317

Table 3 Besides organic acids, water-soluble polymers

Glass transition temperature (Tg) of ethanol-cast shellac films such as HPMC were also investigated as additives
containing different additives as plasticizer (mean value F standard
deviation) to improve the disintegration of shellac films in pH
6.8 buffer. The shellac-HPMC E5 films were clear
Additive Concentration, Tg, jC
% w/w and homogeneous up to 25% (w/w) HPMC E5,
indicating compatibility of the polymers. Films with
None – 39.7 (0.8)
Citrate ester higher amounts of HPMC E5 were turbid and
Triethyl citrate 5 18.7 (0.8) heterogeneous, indicating incompatibility of the pol-
10 14.0 (0.1) ymers. Dry shellac-HPMC E5 films were harder than
Organic acids the pure shellac films as shown by similar low
Sorbic acid 5 15.3 (1.0)
10a 9.0 (2.3)
Benzoic acid 5 11.6 (0.3)
10a 8.0 (0.6)
Adipic acid 5 10.8 (0.8)
10a 8.6 (0.5)
a
Crystals present in the film.

(Fig. 1B, < 10%). Therefore, sorbic acid or TEC or

shellac components did not leach from the films at low
pH, indicating good resistance towards low pH media.
In contrast, in pH 6.8 buffer, the films took up media in
excess of 50% and also a significant weight loss was
observed. The weight loss and water content increased
with increasing additive concentration and was higher
with sorbic acid than with TEC. Sorbic acid has a pKa
of 4.76 [19] and was therefore unionized in 0.1 N HCl,
but fully ionized in pH 6.8 buffer, thus promoting the
media uptake. In contrast, TEC is an ester and does not
dissociate. All sorbic acid-containing films were
opaque and swollen in pH 6.8 buffer.
The mechanical properties of ethanol-cast shellac
films were investigated with TEC and sorbic acid as
plasticizers/pore-formers and HPMC as a pore-former
in the dry and wet state (Table 4). Wet, additive-free
shellac films had a higher elongation (10%) than the
very brittle dry shellac films (1%). Water, which was
taken up by the film, probably acted as plasticizer.
Adding TEC or sorbic acid significantly increased the
flexibility of the films as indicated by elongation
values in the range of 35– 120% for dry films and
37 –55% for wet films. Higher amounts of additive
resulted in increased elongation values. Correspond-
ingly, the puncture strength and modulus at puncture
decreased. In general, sorbic acid-plasticized films
Fig. 1. Effect of the concentration of additives on the dry weight
had higher modulus values in the dry state and lower loss and water content of ethanol-cast shellac films upon exposure
modulus values in the wet state when compared with to simulated gastric and intestinal fluid for 120 min, (A) dry weight
TEC-plasticized films. and (B) water content.
318 N. Pearnchob et al. / Journal of Controlled Release 94 (2004) 313–321

Table 4
Mechanical properties of ethanol-cast shellac films containing different additives in the dry and wet state after exposure to simulated gastric
juice (0.1 N HCl) for 120 min (mean value F standard deviation)
Additive, % w/w Elongation, % Puncture strength, MPa Modulus at puncture, kPa
Dry Wet Dry Wet Dry Wet
None 1.0 (0.1) 10.1 (2.5) 1.7 (0.7) 1.9 (0.2) 67.5 (43.6) 19.8 (3.7)
TEC
5 76.1 (18.6) 37.4 (3.8) 0.5 (0.1) 1.5 (0.3) 6.2 (1.4) 66.6 (12.1)
10 120.8 (11.0) 40.2 (7.2) 0.5 (0.1) 1.1 (0.2) 5.9 (1.0) 61.9 (9.4)
Sorbic acid
5 35.6 (2.5) 45.3 (0.6) 1.9 (2.8) 1.2 (0.1) 53.3 (1.8) 20.5 (5.6)
10 107. 6 (54.6) 54.6 (0.0) 1.6 (0.2) 1.3 (0.2) 19.4 (7.7) 21.0 (2.3)
HPMC E5 (in addition to 10% w/w TEC)
25 2.4 (0.5) 2.3 (0.5) 4.6 (1.4) 0.2 (0.1) 329.1 (55.2) 21.0 (0.0)

elongation values, but a higher puncture strength and Only 10% sorbic acid reduced the disintegration time
therefore a higher modulus at puncture. This increase to approx. 5 –25 min at coating levels between 8 and
in the film hardness was due to an increase in Tg 12 mg/cm2. Sorbic acid was less effective in decreas-
caused by HPMC, which had a Tg between 154 and ing the disintegration time at levels of 5% and 7.5% at
180 jC [20,21], whereas pure shellac films had a higher coating levels in excess of 10 mg/cm2.
relatively low Tg at 40 jC. As expected, the leaching In the dry state, the shellac-coated soft gelatin
of HPMC E5 in 0.1 N HCl resulted in a weakening capsules are quite hard, irrespective of the addition
of shellac films, as indicated by the low values of of additives (hardness 230 –250 N) (Table 5). Upon
elongation and puncture strength. Within 120 min, exposure to simulated gastrointestinal media, the
the films lost their integrity and, therefore, weight hardness decreased for all formulations. Capsules,
loss studies could not be performed. which were coated with shellac containing either
Soft gelatin capsules were coated with various
shellac-additive formulations. At coating levels above
7 mg/cm2, all shellac-coated soft gelatin capsules
except capsules coated with shellac containing 5%
adipic acid remained intact in 0.1 N HCl for 2
h according to pharmacopoeial requirements. Because
of the solubility of adipic acid in 0.1 N HCl (Table 1),
adipic acid leached from the shellac coating resulting
in premature disintegration in 0.1 N HCl. In contrast,
sorbic acid was less soluble in 0.1 N HCl (1– 2 mg/
ml) and the capsules stayed intact. The disintegration
time of shellac-coated soft gelatin capsules in phos-
phate buffer pH 6.8 increased with increasing coating
level and was strongly dependent on the type of
additive (Fig. 2). With 5% TEC-plasticized films, a
coating level of 7 mg/cm2 provided gastric resistance
and subsequent disintegration in phosphate buffer pH
6.8 within 60 min; however, higher coating levels
extended the disintegration time over 60 min. The
addition of 5 – 10% sorbic acid or 25% HPMC E5
significantly reduced the disintegration time in phos- Fig. 2. Effect of the type of additive and coating level on the
phate buffer pH 6.8 at coating levels below 10 mg/ disintegration times of ethanolic shellac-coated soft gelatin capsules
cm2. Sorbic acid was more effective than HPMC. in phosphate buffer pH 6.8, after 120 min in 0.1 N HCl.
 N. Pearnchob et al. / Journal of Controlled Release 94 (2004) 313–321 319

Table 5 The decrease in gastric protection of ethanolic

Mechanical properties of ethanolic shellac-coated soft gelatin shellac coatings was explained by the esterification
capsules containing different additives in simulated gastrointestinal
fluid (coating level, 9 – 10 mg/cm2; 120 min in 0.1 N HCl, then 10 between the carboxylic acid groups and the alcoho-
or 30 min in phosphate buffer pH 6.8) (mean value F standard lic hydroxyl groups of shellac. This reaction was
deviation) prevented by using the ammonium salt of shellac
Additive, Hardness, N acids in the film formation process from aqueous
w/w Dry state 0.1 N HCl pH 6.8 pH 6.8 alkaline solution [9]. Therefore, in contrast to aque-
(120 min) (10 min) (30 min) ous-cast films, ethanol-cast films showed a higher
TEC, 5% 244.2 205.1 151.8 125.1 weight loss in pH 6.8 buffer (Fig. 1A) and weaker
(37.3) (21.6) (19.6) (16.1) mechanical properties [modulus 84 kPa (aqueous-
Sorbic acid, 5% 252.6 76.9 71.7 40.9 cast films) vs. 9 kPa (ethanol-cast films)]. The
(44.4) (23.5) (18.5) (19.0) addition of sorbic acid significantly increased the
Shellac plasticized with 10% w/w TEC
weight loss in pH 6.8 buffer only for ethanol-cast
HPMC E5, 25% 230.9 89.1 63.7 44.6
(20.2) (5.8) (20.3) (2.7) films (Fig. 1A), while the addition of hydrophilic
polymers like gelatin, alginic acid and HPMC ef-
fectively changed the weight loss of aqueous-cast
sorbic acid or HPMC, became softer in the disinte- films (Table 6) because of the leaching of the
gration media when compared to TEC-plasticized additives.
shellac-coated soft gelatin capsules, which remained The hardness of aqueous shellac-coated soft
fairly hard. This correlated well with the modulus gelatin capsules was correlated with the cor-
values of wet films (Table 4), where TEC-containing responding disintegration behavior (Table 7). In
films had the highest values for modulus. The hard- the dry state, the aqueous shellac-coated soft gelatin
ness of the wet capsules with sorbic acid or HPMC capsules had a hardness between 145 and 200 N.
was significantly decreased to below 100 N in both After exposure to 0.1 N HCl for 120 min, all
media, the hardness decreased further with increasing coated soft gelatin capsules had a much lower
time in pH 6.8 buffer because of a continued water hardness (55 – 85 N), but did not disintegrate. The
uptake and dissolution of the shellac coating. This hardness further decreased after 30 (15 – 29 N) and
correlated with the disintegration times of cast films in 60 min ( < 10 N) in phosphate buffer pH 6.8. Both
pH 6.8 buffer, whereby the sorbic acid- of HPMC- types of additive-free shellac coated capsules
containing capsules disintegrated more rapidly than (unplasticized and TEC-plasticized) kept the original
shellac films with only TEC (Fig. 2).
As an alternative to coating with alcoholic solu-
Table 6
tions, shellac can also be coated from aqueous alka- Relationship between dry weight and water content of shellac films
line solutions, thus avoiding organic solvents. The dry prepared from ammoniated aqueous solution (120 min in 0.1 N HCl,
weight after leaching and the water content of aque- then 60 min in phosphate buffer pH 6.8) (mean value F standard
ous-cast shellac films containing different hydrophilic deviation)
additives upon exposure to gastrointestinal fluids were Additive, Dry weight, % Water content, %
investigated (Table 6). In general, the aqueous-cast w/w 0.1 N HCl pH 6.8 0.1 N HCl pH 6.8
films swelled in 0.1 N HCl (18 –40%) with only a None 99.6 (0.0) 98.5 (0.6) 23.8 (1.7) 54.4 (1.7)
negligible loss of film components. Only HPMC- Sorbic acid, 99.5 (0.2) 99.7 (0.0) 17.8 (0.3) 65.9 (0.1)
containing films lost approx. 6% in 0.1 N HCl, 5%
probably because of its pH-independent and high
solubility. Sorbic acid and Na Alginate probably did Shellac films plasticized with 5% w/w TEC
None 99.2 (0.7) 98.4 (0.6) 27.6 (2.9) 51.1 (0.2)
not leach because of their low solubility at low pH. Gelatin, 10% 99.5 (0.2) 72.6 (3.3) 37.9 (0.4) 68.9 (1.9)
The water content of the aqueous cast films was Alginic acid, 99.4 (0.6) 70.2 (0.7) 37.2 (3.0) 66.5 (6.3)
higher than the one of the organic cast films (Fig. 10%
1B), probably because of the presence of shellac HPMC E5, 94.4 (1.3) 62.8 (3.1) 40.3 (1.1) 67.2 (2.7)
components in the salt form. 25%
320 N. Pearnchob et al. / Journal of Controlled Release 94 (2004) 313–321

Table 7 taining the hydrophilic additive would probably be

Mechanical properties and disintegration behavior of ammoniated ruptured by intestinal motility. The HPMC-shellac
aqueous shellac-coated soft gelatin capsules containing different
pore-formers (coating level, 19 – 23 mg/cm2; 120 min in 0.1 N HCl, coated capsules did not provide enteric properties,
then phosphate buffer pH 6.8) (mean value F standard deviation) the capsules disintegrated already within 20 min in
Additive, Hardness, N Disintegration 0.1 N HCl.
w/w Dry 0.1 N HCl pH 6.8 pH 6.8 time in pH
state (120 min) (30 min) (60 min) 6.8, min
None 185.8 85.5 17.9 9.3 60a 4. Conclusions
(28.0) (20.6) (2.0) (3.3)
Sorbic 145.0 75.5 15.5 9.6 25 – 30a The disintegration behavior of enteric shellac-coat-
acid, (23.6) (3.9) (3.9) (3.0) ed soft gelatin capsules in simulated intestinal fluids
5%
was improved. With ethanolic or aqueous shellac
Shellac films plasticized with 5% w/w TEC solution, the addition of appropriate types and amount
None 200.9 67.0 14.5 5.4 60a of additives (e.g., organic acids, hydrophilic poly-
(32.9) (15.5) (2.0) (1.8) mers) effectively accelerated the disintegration times
Gelatin, 200.9 84.7 29.3 4.8 25 – 30a in phosphate buffer pH 6.8 while retaining the gastric
10% (32.9) (13.9) (6.0) (9.3)
Alginic 159.9 55.0 14.6 6.8 25 – 30a
protection in 0.1 N HCl.
acid, (21.3) (15.9) (7.1) (5.5)
10%
HPMC 174.5 capsules Acknowledgements
E5, (27.5) disintegrated
25% in 0.1 N HCl
after 20 min The financial support of the Forschungsvereini-
a
Capsule cores softened and swelled, but film coating remained gung der Arzneimittelhersteller (FAH) and of the
intact. Arbeitsgemeinschaft industrieller Forschungsvereini-
gungen (AiF) is acknowledged.
shape for longer than 60 min without disintegration.
The ethanolic shellac-coated capsules containing
hydrophilic additives disintegrated (Fig. 2), whereas References
the aqueous shellac-coated capsules softened but
[1] W.G. Chambliss, Enteric coatings, in: J. Swarbrick, J.C. Boy-
did not disintegrate (Table 7). This was explained lan (Eds.), Encyclopedia of Pharmaceutical Technology, vol.
again by the esterification in ethanolic shellac coat- 5, Marcel Dekker, New York, 1992, pp. 189 – 200.
ings, and by the wet mechanical properties (in pH [2] J.E. Hogan, Modified release coatings, in: G. Cole, J.E.
6.8 buffer) of ethanol-cast and aqueous-cast films. Hogan, M. Aulton (Eds.), Pharmaceutical Coating Technol-
For pure, unplasticized films, aqueous-cast films ogy, Taylor & Francis Books, London, 1995, pp. 409 – 438.
[3] C.T. Rhodes, S.C. Porter, Coatings for controlled-release drug
had a similar elongation to ethanol-cast films delivery systems, Drug Dev. Ind. Pharm. 24 (12) (1998)
(26 – 27%), but had a higher modulus at puncture 1139 – 1154.
than ethanol-cast films (84 vs. 9 kPa). As a result, [4] C.T. Rhodes, S.C. Porter, Coatings, in: E. Mathiowitz (Ed.),
aqueous-cast films were harder, although aqueous- Encyclopedia of Controlled Drug Delivery, John Wiley &
cast films took up more medium (Table 6) than Sons, New York, 1999, pp. 299 – 311.
[5] S.H.W. Wu, D.M. Wyatt, M. Adams, Chemistry and applica-
ethanol-cast films (Fig. 1B). The aqueous shellac- tions of cellulosic polymers for enteric coatings of solid dos-
coated soft gelatin capsules with hydrophilic addi- age forms, in: J.W. McGinity (Ed.), Aqueous Polymeric
tives expanded in size, and the gelatin shells Coatings for Pharmaceutical Dosage Forms, Marcel Dekker,
softened and swelled after immersion in the pH New York, 1997, pp. 385 – 418.
6.8 buffer solution for 25– 30 min. Although all [6] H.S. Cockeram, S.A. Levine, The physical and chemical prop-
erties of shellac, J. Soc. Cosmet. Chem., (1961) 316 – 323.
aqueous shellac-coated soft gelatin capsules [7] R.C. Vasavada, Shellac, in: A. Wade, P.J. Weller (Eds.), Hand-
remained intact over a period of 60 min in pH book of Pharmaceutical Excipients, American Pharmaceutical
6.8 buffer, the softer and hydrated capsules con- Association, Washington, DC, 1994, pp. 422 – 423.
 N. Pearnchob et al. / Journal of Controlled Release 94 (2004) 313–321 321

[8] S.C. Smolinske, Handbook of Food, Drug and Cosmetic Ex- [15] R. Bodmeier, O. Paeratakul, Mechanical properties of dry and
cipients, CRC Press, Boca Raton, FL, 1992. wet cellulosic and acrylic films prepared from aqueous colloi-
[9] F. Specht, M. Saugestad, T. Waaler, B.W. Müller, The appli- dal polymer dispersions used in the coating of solid dosage
cation of shellac as an acidic polymer for enteric coating, forms, Pharm. Res. 11 (1994) 882 – 888.
Pharm. Technol. Europe 10 (1998) 20 – 28. [16] M. Lynch, Fumaric acid, in: A. Wade, P.J. Weller (Eds.),
[10] N. Pearnchob, J. Siepmann, M. Sturm, R. Bodmeier, Shellac Handbook of Pharmaceutical Excipients, American Pharma-
used for moisture protective and taste masking coatings: effect ceutical Association, Washington, DC, 1994, pp. 197 – 198.
of formulation and processing variables, Proceedings 4th [17] C.A. Entwistle, R.C. Rowe, Plasticization of cellulose ethers
World Meeting on Pharmaceutics, Biopharmaceutics and used in the film coating of tablets, J. Pharm. Pharmacol. 31
Pharmaceutical Technology, ADRITELF/APGI/APV, Flor- (1979) 269 – 272.
ence, Italy, April 8 – 11, 2002. [18] C. Wu, J.W. McGinity, Non-traditional plasticization of poly-
[11] J.E. Hogan, Film-coating materials and their properties, in: G. meric films, Int. J. Pharm. 177 (1999) 15 – 27.
Cole, J.E. Hogan, M. Aulton (Eds.), Pharmaceutical Coating [19] D.J. Harper, Sorbic acid, in: A. Wade, P.J. Weller (Eds.),
Technology, Taylor & Francis Books, London, 1995, pp. 6 – 52. Handbook of Pharmaceutical Excipients, American Pharma-
[12] J.T. Carstensen, Advanced Pharmaceutical Solids, Marcel ceutical Association, Washington, DC, 1994, pp. 470 – 472.
Dekker, New York, 2001. [20] P. Sakellariou, R.C. Rowe, E.F.T. White, The solubility
[13] J.B. Dressman, B.Ø. Palsson, A. Ozturk, S. Ozturk, Mech- parameters of some cellulose derivatives and polyethylene
anisms of release from coated pellets, in: I. Ghebre-Sell- glycols used in tablet film coating, Int. J. Pharm. 31 (1986)
assie (Ed.), Multiparticulate Oral Drug Delivery, Marcel 175 – 177.
Dekker, New York, 1994, pp. 285 – 306. [21] R.J. Harwood, J.L. Johnson, Hydroxypropyl methylcellulose,
[14] R. Bodmeier, O. Paeratakul, Dry and wet strength of polymeric in: A. Wade, P.J. Weller (Eds.), Handbook of Pharmaceutical
films prepared from an aqueous colloidal polymer dispersion, Excipients, American Pharmaceutical Association, Washing-
EudragitR RS30D, Int. J. Pharm. 96 (1993) 129 – 138. ton, DC, 1994, pp. 229 – 232.