Research on film coating formulation of sustained release pellets of verapamil hydrochloride
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
RESEARCH ON FILM COATING FORMULATION OF SUSTAINED
RELEASE PELLETS OF VERAPAMIL HYDROCHLORIDE
Truong Duc Manh1, Vo Xuan Minh2, Phan Thi Hoa1
Nguyen Van Bach1, Dinh Dinh Chinh3
SUMMARY
Objectives: To determine the optimized parameters of the technical process and the
adequate excipient ingredients of the pellet film c oat which control release to develop the
basic formula of the sustained release (SR) pellet of Verapamil hydrochloride (VER.HCl).
Materials and method: Prepare SR VER.HCl pellet with film coating using Mini-Glatt
fluidized bed; quantify VER.HCl with UV spectroscopy method; examine the effect of excipients
(EC, HPMC, DBP, TEC and Talc) on the dissolution of SR VER.HCl pellet. Results: With
excipients EC N20, HPMC E15, HPMC E5, TEC and Talc, the release rate of VER.HCl was
9.02%, 26.55%, 48.90% and 83.73% at the time of 1, 2, 4 and 8 hours, respectively.
Conclusion: EC N10, HPMC E15 and HPMC E5 controlled release excipients suitable for
formula of SR VER.HCl pellet film 120 mg.
* Keywords: Verapamil hydrochloride; Pellet; Sustained release; Preparation.
INTRODUCTION
frequency for patients, the study of SR
VER.HCl pellet preparation is essential
[4, 5]. In the formulation of SR VER.HCl
pellet, controlled release film coating
ingredients play a critical role, greatly
influencing the rate and degree of
pharmaceutical substance release from
the drug form and drug bioavailability.
Through this study, we aimed: To produce
the results of investigating the effects of
certain parameters of the technical process
and controlled release film coating excipient
as the basis for developing the basic
formulation of SR VER.HCl pellet film
120 mg.
Verapamil hydrochloride (VER.HCl) is
a calcium channel blocker used to treat
angina pectoris, hypertension and
arrhythmia. VER.HCl is completely
absorbed in the gastrointestinal tract
(about 90%), but the bioavailability is only
20 - 35% due to its rapid metabolism
through liver. This pharmaceutical
substances have a short half - life
(2.8 - 7.4 hours) causing patients to
administer many times a day [1, 2, 3].
Therefore,
in
order
to
improve
bioavailability and reduce the dosing
1Vietnam Military Medical University
2Hanoi University of Pharmacy
3Military Central Hospital 108
Corresponding author: Truong Duc Manh (manhxn150@yahoo.com)
Date received: 19/02/2021
Date accepted: 26/4/2021
143
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
MATERIALS AND METHODS
1. Materials and equipment
Add plasticizer to the solution above, stir
to homogenize. Crush talcum powder, sift
through a 125 µm sieve. Add 96% ethanol
and grind thoroughly, and pull gradually
into the beaker containing coating solution.
Stir the solution on a magnetic stirrer for
about 30 minutes. Filter through a 125 µm
sieve to obtain a homogeneous coating
solution. Make up to the needed volume
with 96% ethanol. The solution was
stirred continuously on a magnetic stirrer
throughout the coating process.
*Materials and chemicals: VER.HCl
Standard: Provided by Ho Chi Minh City
Drug Quality Control Institute (QT242010914,
concentration 100.52%), Pharmaceutical
VER.HCl: USP 38 (China), HPMC E6,
E15: USP 38 (China), Talc: USP 38 (China),
EC N10, N20: USP 38 (China), DBP:
USP 38 (India), TEC: USP 38 (China),
Ethanol 96%: Vietnamese Pharmacopoeia IV.
*Equipment and tools: Mini-Glatt film
coating fluidized bed (Germany), Copley
DIS 8000 dissolution tester (UK), Labomed
UV-VIS spectrophotometer UVD-2960
- Put pellets in the coating equipment:
Dry pellets for about 15 minutes to heat
up before spraying on the coating. Spray
the coating solution. Keep spraying until
(USA), analytical balance Mettler Toledo coating solution runs out, leave the
equipment on for another 15 minutes.
with readability down to 0.1 mg
(Switzerland), PHARMATEST PTF
E
Table 1: Parameters of the coating
abrasion tester (Germany), ERWEKA
SVM powder and granule tapped volume
tester (Germany), ERWEKA GWF granular
tester (Germany), sieve analysis (China)
and other tools meeting laboratory and
analytical testing standards.
process.
Spray pressure
to be determined
to be determined
to be determined
55 5°C
Spray rate
Fluidizing air volume
Inlet air temperature
Outlet air temperature
Spray gun diameter
42 1°C
2. Methods
1.2 mm
*Preparation of VER.HCl controlled
release pellets by pan coating technique:
- The obtained pellets were dried at
60°C for 6 hours and left overnight for the
coating film to stabilize, then sifted to
retain diameter of 0.8 - 1.5 mm.
SR VER.HCl pellet was prepared by
coating a release control film onto the
core pellet which is
a
composition
- Film coating performance: calculated
by the formula:
including: EC (release control polymer),
HPMC (creating diffusion channel), DBP,
TEC (plasticizer), Talc (anti-sticking agent),
96% ethanol (solvent). The process of
coating release control film was carried
out in steps as follows:
m1− m2
Film-coating efficiency (%) =
x 100%
m3
Of which: m1: Total weight of pellet
after coating (g);
m2: Weight of core pellet before
coating (g);
- Prepare coating solution: Soak and
dissolve completely EC in approximately
2/3 of 96% ethanol, add HPMC to dissolve.
m3: Weight of solids in the formula of
film coat (g).
144
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
* Drug content:
+ Equipment: Stirrer.
- Test sample: Weigh approximately 2g
of pellet, grind into fine powder. Precisely
weigh the corresponding amount of fine
powder to roughly 50 mg of VER.HCl.
Transfer to a 50 mL beaker. Add
approximately 30 mL of pH 7.5 phosphate
buffer solution. Shake in ultrasonic shaker
for 60 mins. Transfer to a 50 mL
volumetric flask, add phosphate buffer of
pH 7.5 to the mark and mix well. Filter
through a filter paper, discard roughly 10
mL of the primary filtrate, the remaining
filtrate was solution A. Pipette 0.5 mL of
solution A into a 10 mL volumetric flask,
make up to the mark with pH 7.5 phosphate
buffer solution and mix. Read the solution
in spectrophotometer at a wavelength
λ = 278 nm. Simultaneously carry out the
same procedure with the standard solution
under the same conditions. The content
of pharmaceutical substances in pellet
was calculated by the following formula:
+ Stirring speed: 50 2 rpm.
+ Temperature: 37.0 0.5°C.
+ Medium: 900 mL of phosphate buffer
solution of pH 7.5.
+ Sampling time: At interval of 1, 2, 4
and 8 hours.
+ Test sample: Pellet quantity equivalent
to 120 mg VER.HCl
+ Quantify pharmaceutical substances
released at sampling times by measuring
the absorbance at a wavelength of 278 nm.
Calculate the amount of pharmaceutical
substances release based on the reference
point of VER.HCl in pH 7.5 phosphate
buffer medium using UV-VIS spectroscopy
method.
RESULTS AND DISSCUSION
1. Results of investigation of the
effects of certain parameters in the
technical procedure
In order to determine the adequate film
coating parameters, fundamental pellet
film formula includes: Core pellets of
VER.HCl: 20.00g; EC N10: 3.00g; DEP:
0.24 g; Talc powder: 1.50g; Ethanol 96%:
50 mL.
At.mc
% VER.HCl ⁄pellet=
x 100 (%)
Ac.mt
Of which: At: Optical density of sample
solution;
Ac: Optical density of standard solution;
mc: Weight of VER.HCl standard weight
- Effects of coating solution spray rate:
to quantify;
The coating solution spray rate varied
at 0.45 mL/min; 0.85 mL/min and 1.25
mL/min. Core pellet of VER.HCl was
overcoated with coating parameters and
the results were shown as below:
mt: Weight of pellet to quantify.
* In vitro dissolution studies:
Testing conditions: complied to USP 41 [5]
under the following specific conditions:
145
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
Table 1: Results of effects of coating solution spray rate on the coating process.
No.
1
Parameters
Fluidizing air volume (m3/hour)
Spray pressure (bar)
Inlet air temp (°C)
Value
18
2
1.2
3
55
42
5
1
4
Outlet air temp (°C)
5
Spray gun diameter (mm)
Spray rate (mL/min)
1.2
6
0.45
0.85
1.25
-
Coating efficiency (%)
60.76
73.21
Results
Uniform coat, stabilized pellet Pellet agglutination
fluidizing
Physical properties
Spray rate increasing from 0.85 to 1.25 mL/min resulted in pellet agglutination.
Whereas spray rate at 0.45 and 0.85 mL/min led to stabilized coating fluidizing results.
However, the coating efficiency at 0.45 mL/min was lower due to slower spray rate and
fast evaporation rate of the coating solution solvent. Therefore, spray rate of 0.85 mL/min
was selected in the next studies to increase optimization.
- Effects of spray pressure:
In order to determine the optimized spray pressure, various spray pressures were
used while other parameters were kept constant: Fluidizing air volume: 18 m3/hour,
spray rate: 0.85 mL/min, inlet air temp: 55 5°C, outlet air temp: 42 1°C, spray gun
diameter: 1.2 mm. The testing parameters used to determine spray pressure and their
results are demonstrated in table 2.
Table 2: Results of effects of spray pressure on the coating process.
Parameters
Spray pressure (bar)
Results
Value
1.0
1.2
1.4
Coating efficiency (%)
-
73.21
67.30
Uniform coat, stabilized
pellet fluidizing
Physical properties
Pellet agglutination
Pellet pulverization
Low spray pressure (1.0 bar) increased spray droplet sizes, reduced evaporation
rate and enhanced pellet agglutination. In contrast, higher spray pressure (1.4 bar)
caused pellet pulverizations, reduced spray droplet sizes, enhanced evaporation rate,
altogether resulting in efficiency loss. The technical specifications of equipment greatly
affected coating performance as well as the quality of the pellet film. Therefore, spray
pressure of 1.2 bar was selected to be used in the next studies.
146
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
- Effects of fluidizing air volume:
In order to determine the optimized fluidizing air volume, various fluidizing air
volumes were used while other parameters were kept constant: spray pressure: 1.2 bar,
spray rate: 0.85 ml/min, inlet air temp: 55 5°C, outlet air temp: 42 1°C, spray gun
diameter: 1.2 mm. The testing parameters and results are shown in table 3.
Table 3: Results of effects of fluidizing air volume.
Parameters
Fluidizing air volume (m3/hour)
Results
Value
12
18
24
Coating efficiency (%)
36.50
73.21
43.88
Ununiformed coat, poor Stabilized pellet Ununiformed coat, strong
pellet fluidizing fluidizing attrition, strong fluidizing
Physical properties
Fluidizing air volume of 12 m3/hour reduced coating efficiency (36.50%) and
ununiformed coating surface due to poor fluidizing which caused pellet core to take on
the next layer of coating solution before the previous one fully evaporated. On the other
hand, poor fluidizing also caused pellets fail to take on the full coating solution volume.
Fluidizing air volume of 24 m3/hour also gave a low efficiency (43.88%). Due to strong
fluidizing, pellets collided with the film sides in which ununiformed pellet surface
resulting from pellets unable to fully take on thecoating solution volume. Also, the solvent
evaporated quickly left the pellet surface dry. Fluidizing air volume of 18 m3/hour
produced the highest efficiency (73.21%), the surface was smooth, uniform and stable.
Subsequently, fluidizing air volume of 18 m3/hour was selected.
From the testing results, the following coating parameters are selected:
Spray pressure: 1.2 bar; spray rate: 0.85 mL/min; ni let air temperature: 55 5°C; outlet
3
air temperature: 42 1°C; spray gun diameter: 1.2mm; fluidizing air volume: 18 m /hour.
2. Results of determining the effects of the release control film formulation
- Effects of proportion and type of release control polymer:
Screening studies have found that different proportions of pellet film ingredients
changed the rate of pharmaceutical substance release from pellets. The formulations
designed to determine the effects of the EC proportion were presented in table 4.
Table 4: The formulations designed to determine the optimized EC proportion.
Formulations
Ingredients
F1
F2
F3
F4
F5
-
F6
-
EC N10 (g)
3
4
5
-
EC N20 (g)
-
-
-
3
4
5
DBP (% w/w EC)
Talc (% w/w EC)
EtOH 96% (mL)
6
6
6
6
6
6
50
50
50
50
50
50
50
50
50
50
50
50
Prepare coating solution and carry out coating each batch of 20g core pellets of VER.HCl.
Testing results of the film forming polymer concentration were shown in table 5 and figure 1.
147
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
Table 5: Release rate of VER.HCl during EC proportion testing (n = 6;
SD)
Release rate of VER.HCl over time (hour)
Formulations
1
2
4
8
CT1
CT2
42.08 1.04
21.65 1.13
17.42 0.76
6.91 0.12
6.11 0.05
5.67 0.02
2 - 12
72.74 1.66
47.43 1.12
31.70 0.90
8.95 0.43
7.18 0.10
5.68 0.02
10 - 25
86.84 1.03
67.92 1.98
61.20 1.40
18.83 0.82
11.07 0.37
5.82 0.05
25 - 50
101.19 1.53
95.21 1.97
83.29 3.35
29.76 1.05
13.32 0.75
6.15 0.07
> 80
CT3
CT4
CT5
CT6
USP 41 (%)
CT1
CT4
CT2
CT5
CT3
CT6
120
100
80
60
40
20
0
0
1
2
3
4
5
6
7
8
9
Time (hour)
Figure 1: The release rate of VER.HCl over time during EC proportion testing.
Increased proportion of both types of EC in the film ingredients reduced the release
rate of VER.HCl as when the EC proportion increases, the pellet film thickness also
increases, thereby increasing the diffusion distance leading to a decrease in the
release rate of pharmaceutical substance to the dissolved medium. With EC N10 film
forming polymer, all three formulations yielded higher rate of pharmaceutical substance
release than criteria in USP41. Particularly, at 1 hour, all three formulations CT1, CT2
and CT3 showed the release rate of pharmaceutical substance higher than 12%.
4 hours later, it exceeded 50% and these formulations were almost completely
released 8 hours later. The formulation using 5g of EC (CT3 and CT6), the coating had
some difficulties due to the increased viscosity of the film-forming suspension resulting
in pellet agglutination. Thus, EC N10 is not adequate to be used as an ingredient of
release control VER.HCl pellet film. Replace EC N10 with EC N20, all three
formulations adequately controlled rate of pharmaceutical substance release. CT5 and
CT6 gave the lowest rate of drug release due to great film thickness which prevented
VER.HCl from diffusing into the dissolved medium. After 8 hours, both CT5 and CT6
yielded rate lower than 15%. CT4 using 3g of EC N20 was capable of controlling
pharmaceutical substance release. As a result, CT4 was selected for the next studies.
148
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
- Effects of the proportion and type of polymer combination:
As CT4 gave a relatively small rate of pharmaceutical substance release compared
to what was required by USP 41, it was necessary to increase the rate of pharmaceutical
substance release by combining some hydrophilic polymers to create diffusion
channels on the pellet film to enhance the rate. Based on the formulations designed as
in table 6, the dissolution is evaluated and presented as results in table 7 and figure 2.
Table 6: Formulations designed to determine the optimized proportion of polymer
combination.
Formulations
Ingredients
CT4
CT7
CT8
CT9
CT10
3
CT11
3
CT12
3
EC N20 (g)
3
3
3
3
HPMC E6 (% w/w EC)
HPMC E15 (% w/w EC)
DBP (% w/w EC)
Talc (% w/w EC)
EtOH 96% (mL)
0
15.0
0
17.5
0
20.0
0
0
0
0
0
15.0
6
17.5
6
20.0
6
6
6
6
6
50
50
50
50
50
50
50
50
50
50
50
50
50
50
Table 7: Released rate of VER.HCl during polymer combination proportion testing
(n = 6;
SD).
Rate of VER. HCl released over time (hour)
Formulations
1
2
4
8
CT4
CT7
6.91 0.12
7.44 0.13
16.95 0.85
30.06 0.90
7.21 0.36
8.02 0.11
18.02 0.58
2-12
8.95 0.43
17.89 0.83
35.93 0.97
50.12 1.56
8.73 0.13
19.93 0.89
28.88 1.15
10-25
18.83 0.82
38.67 1.16
83.77 2.16
91.27 4.21
16.68 0.79
40.23 0.81
55.03 1.49
25-50
29.76 1.05
66.74 1.38
93.54 2.16
98.66 3.97
27.24 1.06
70.30 2.52
84.34 2.61
> 80
CT8
CT9
CT10
CT11
CT12
USP 41 (%)
120
100
80
CT4
CT10
CT7
CT8
CT9
CT11
CT12
60
40
20
0
0
1
2
3
4
5
6
7
8
9
Time (hour)
Figure 2: The release rate of VER.HCl over time during polymer combination proportion testing.
149
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
Increased amount of HPMC E6 and E15
enhanced the release rate of pharmaceutical proportion:
substance of the formulation due to an
- Effects of HPMC E6 and HPMC E15
Based on HPMC type testing, it was
increase in the number of pharmaceutical
substance diffusion channels. The results
showed that all six formulations increased
the release rate of pharmaceutical
substance compared to F4. With both
types of HPMC used at low levels (CT7
and CT10), the rate after 8 hours of
release was lower than 70% as compared
to high levels (20%), the release rate of the
formulation exceeded the requirement by
USP 41. With two types of polymers,
HPMC E15 controlled release better than
E5 due to its higher viscosity. Based on
the obtained results above, CT11 was
selected (HPMC E15 = 17.5% compared
to EC) to be used in the next studies.
found that HPMC E5 with lower viscosity
would give higher rate of pharmaceutical
substance release in the first hours while
HPMC E15 with higher viscosity would
corrode and swell more slowly enabling it
to control pharmaceutical substance release
in hours that follow. Therefore, it is
necessary to select the combination of
these two polymers to be used in pellet
film ingredients. However, since HPMC
has poorer solubility in ethanol than water,
an additional 5 mL of distilled water should
be used to dissolve HPMC. Based on the
formulations designed as in table 8, the
dissolution was evaluated and presented
as results in table 9 and figure 3.
Table 8: Formulations designed to determine the optimized HPMC E6 and HPMC
E15 combination proportion.
Formulations
Ingredients
CT11
CT13
CT14
3
CT15
3
EC N20 (g)
3
3
HPMC E6 (% w/w EC)
HPMC E15 (% w/w EC)
DBP (% w/w EC)
Talc (% w/w EC)
Distilled water (mL)
EtOH 96% (mL)
0
2.5
15.0
6
5.0
12.5
6
7.5
10.0
6
17.5
6
50
5
50
5
50
5
50
5
50
50
50
50
Table 9: The release rate of VER.HCl during HPMC E6 and HPMC E15 combination
proportion testing (n = 6;
SD).
Release rate of VER. HCl over time (hour)
Formulations
1
2
4
8
CT11
CT13
8.02 0.11
9.31 0.45
13.65 0.54
21.47 0.98
2 - 12
19.93 0.89
26.62 0.82
30.06 2.21
42.33 1.29
10 - 25
40.23 0.81
52.12 1.19
56.81 0.59
65.09 1.44
25 - 50
70.30 2.52
83.21 2.70
89.30 3.50
96.84 3.34
> 80
CT14
CT15
USP 41 (%)
150
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
120
100
80
60
40
20
0
CT11
CT14
CT13
CT15
0
1
2
3
4
5
6
7
8
9
Time (hour)
Figure 3: The release rate of VER. HCl over time during HPMC E6 and
HPMC E15 combination proportion testing.
Reduced HPMC E15/HPMC E6 increased the release rate of pharmaceutical
substance of all formulations due to an increase in the weight of HPMC E5 in the
polymer mixture. The results showed that all three formulations increased the rate
compared to CT11 (without HPMC E5). CT14 and CT15 (using HPMC E5 at 5% and
7.5%) which yielded higher release rate of pharmaceutical substance in the first hours
due to low viscosity accounted for a large proportion in the combined polymer mixture.
They absorbed water and dissolved quickly creating porous diffusion in pellet film, thus
released more pharmaceutical substances than CT13 (HPMC E15 = 2.5% compared to
EC). Based on the findings above, CT13 (HPMC E15 = 2.5% compared to EC) was
selected to be used in the next study.
- Effects of plasticizer:
Testing with two plasticizers, DBP and TEC were conducted. Based on the
formulations designed as in table 10, the dissolution was evaluated and presented as
results in table 11 and figure 4.
Table 10: Formulations designed to determine the optimized plasticizer.
Formulations
Ingredients
CT13
CT16
CT17
CT18
CT19
CT20
EC N20 (g)
3
3
3
3
3
3
HPMC E6 (% w/w EC)
HPMC E15 (% w/w EC)
2.5
2.5
2.5
2.5
2.5
2.5
15.0
15.0
15.0
15.0
15.0
15.0
DBP (% w/w EC)
TEC (% w/w EC)
Talc (% w/w EC)
Distilled water (mL)
EtOH 96% (mL)
6
-
8
-
10
-
-
-
-
6
8
10
50
5
50
5
50
5
50
5
50
5
50
5
50
50
50
50
50
50
151
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
Table 11: Release rate of VER.HCl during plasticizer testing (n = 6;
SD).
Release rate % of VER. HCl over time (hour)
Formulations
1
2
4
8
CT13
CT16
9.31 0.45
8.99 0.14
8.58 0.42
10.45 0.36
12.71 0.43
18.31 0.85
2 - 12
26.62 0.82
19.31 0.59
17.71 0.88
30.51 1.28
30.09 1.23
39.29 1.53
10 - 25
52.12 1.19
42.16 1.34
39.56 1.27
50.04 1.70
55.04 1.93
58.75 1.68
25 - 50
83.21 2.70
76.11 1.84
69.35 2.97
86.56 3.88
90.49 3.60
97.09 4.32
> 80
CT17
CT18
CT19
CT20
USP 41 (%)
120
100
80
CT13
CT18
CT16
CT19
CT17
CT20
60
40
20
0
0
1
2
3
4
5
6
7
8
9
Time (hour)
Figure 4: Release rate (%) of VER. HCl over time during plasticizer testing.
Increased proportion of DEP in pellet film formulations would reduce film
permeability as DEP, a known hydrophobic plasticizer, lower pharmaceutical
substance release rate. Specifically: CT16 and CT17 with large DEP proportions
reduced pharmaceutical substance release rate more clearly than CT13. These two
formulations released less than 80% pharmaceutical substance after 8 hours. In the
case of TEC plasticizer, a hydrophilic plasticizer, higher proportion of TEC would result
in higher rate of pharmaceutical substance release. During the preparation process,
DBP was also found to be difficult to dissolve in 96% ethanol, the coating solution
easily formed a sheen on the surface. It was difficult for DBP to disperse to uniformly
plasticize the film surface. Based on the findings above and to be in line with the USP
41 standard on solubility, CT18 with TEC proportion of 6% of EC weight is selected to
be used in the next study.
152
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
- Effect of anti-sticking agent:
Testing out formulations with different talc proportions as shown in table 12 and
coating on 20g pellets with 50 mL of coating solution containing approximately 10%
solids with similar coating performance. Dissolution evaluation results are shown in
table 13 and figure 5.
Table 12: Formulations designed to determine the optimized anti-sticking agent.
Formulations
Ingredients
CT18
CT21
CT22
CT23
3
EC N20 (g)
3
3
3
HPMC E6 (% w/w EC)
HPMC E15 (% w/w EC)
Talc (% w/w EC)
TEC (% w/w EC)
Distilled water (mL)
96% EtOH (mL)
2.5
15.0
50
6
2.5
15.0
60
6
2.5
15.0
40
6
2.5
15.0
30
6
5
5
5
5
50
50
50
50
Table 13: Release rate of VER.HCl during anti-sticking agenttesting (n = 6;
SD).
Release rate % of VER. HCl over time (hour)
Formulations
1
2
4
8
CT18
CT21
10.45 0.36
22.90 1.02
9.02 0.14
32.65 1.24
2 - 12
30.51 1.28
46.90 2.03
26.55 1.20
60.11 1.65
10 - 25
50.04 1.70
79.54 3.09
48.90 1.42
90.59 3.37
25 - 50
86.56 3.88
97.33 3.69
83.73 2.70
98.18 4.09
> 80
CT22
CT23
USP 41 (%)
120
100
80
CT18
CT22
CT21
CT23
60
40
20
0
0
1
2
3
4
5
6
7
8
9
Time (hour)
Figure 5: The rate of VER. HCl released over time during anti-sticking agent testing.
153
Journal OF MILITARY PHARMACO - MEDICINE N04 - 2021
With a small talc proportion (30%), the pellet fluidizing was stable, uniform and
release rate of pharmaceutical substance smooth surface finish was achieved.
obtained was more than 30%. The cause
- Having selected release control
may be due to the insufficient amount of
excipients EC N20 as well as two
talc which failed to prevent agglutination
hydrophilic polymers, HPMC E15/E6,
during the coating process, ultimately
to create diffusion channels, from which
causing agglutination and puncture in pellet
the pellet film formulation is formulated
films. As for the large talc proportion (60%),
consisting of: EC N20, HPMC E6, HPMC E15,
high rate of pharmaceutical substance
Talc, TEC, distilled water and EtOH 96%.
release was also obtained (22.9% after
1 hour) for which the reason was that an
REFERENCES
excessive amount of talc powder led to
1. Ministry of Health. Vietnamese National
unstable and cracked films when
Drug Formulary. Medical Publishing House
measuring solubility. CT18 and CT22
2015.
have similar solubility curves, the less the
2. Anthony CM, et al. Clarke’ s analysis of
amount of talc, the slower pharmaceutical
drugs and poisons. Pharmaceutical Press.
substance is to release. It was observed
London 2011: 2223-2224.
that CT22 released more slowly and gave
3. Sweetman SC, et al. Martindale 36th,
the release rate of pharmaceutical
RPS Publishing 2009:1522-1526.
substance at all hours closer to what is
4. Nitin DJ, Dipak DG, Ashish AH, et al.
stipulated by USP 41.
Formulation development and evaluation of
sustained release pellets of verapamil HCl.
CONCLUSIONS
International Journal of Pharma Research and
- Having determined the effects of
Development 2010; 1(11):1-7.
certain parameters of the technical film
5. Vidyadhara S, Prasad MB, Sasidhar
coating process to control the release of
RLC, et al. Development and evaluation of
core pellet of VER.HCl. With parameters
controlled release verapamil hydrochloride
such as: Spray pressure: 1.2 bar, spray
pellets by pan coating process. Current
rate: 0.85 mL/min, fluidizing air volume:
18 m3/hour, inlet air temperature: 55 5°C,
Trends in Biotechnology and Pharmacy 2013;
7(1):535-543.
outlet air temperature: 42
1°C, spray
6. USP 41-NF 36. Monographs: Verapamil
hydrochlorid extended-release tablets 2018;
4307-4311.
gun diameter: 1.2 mm, the coating process
gave a high efficiency (73.21%) in which
154
12 trang
15/04/2022
1880
Bạn đang xem tài liệu "Research on film coating formulation of sustained release pellets of verapamil hydrochloride", để tải tài liệu gốc về máy hãy click vào nút Download ở trên
File đính kèm:
- research_on_film_coating_formulation_of_sustained_release_pe.pdf
