formulation and evaluation of pulsatile...
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Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
1
INTERNATIONAL JOURNAL OF TRENDS IN PHARMACY AND
LIFE SCIENCES (IJTPLS)
FORMULATION AND EVALUATION OF PULSATILE DRUG
DELIVERY SYSTEM OF MELOXICAM BY USING PRESS COATED
METHOD
B. Anjali & N. Srinivas
Malla Reddy Institute of Pharmaceutical Sciences, Dhulapally, Secunderabad.
Telangana- 500014
E.Mail: [email protected] ABSTRACT
The objective of the present work was to develop a pulse type profile of formulation
of Meloxicam by using compression coating technique. The formulation is administered at
bed-time provides nocturnal recovery of gastric acid secretion by releasing drug from
formulation in time controlled manner. The use of hydrophilic polymer with erodible and
gellable properties in the dry coating development of pulse type drug release achieved.
Compression coating tablets utilizing Hydroxy propyl cellulose in the outer shell gives
timed release profile. Drug was released burst when complete erosion of shell when low
viscosity grade (erodible polymer) HPC was used. By combining different HPC viscosity
grades it is possible to obtain a time-lags of 3 to 9 Hr with different core composition with
different release kinetics. Effect of rupturable material (EC) combined with erodible
material (Klucel EXF) in the outer shell was studied it was observed using EC alone lag
time is lowest as compared to any weight ratio of EC/HPC-EXF. F2 formulation was best
formulation with ratio Klucel EXF: EC N 20 (87.5: 12.5) showed 6 Hr release.
Key Words: Meloxicam, Pulsatile Drug Delivery System, Klucel EXF, Ethyl Cellulose.
Corresponding Author’s Address:
Ms. B. Anjali,
Malla Reddy Institute of Pharmaceutical Sciences,
Dhulapally, Secunderabad.
Telangana- 500014
E.Mail: [email protected]
Research article
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
www.ijtpls.com
Volume: 1, Issue: 1
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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INTRODUCTION
From many decades conventional dosage forms like Tablets, capsules, pills, powders,
parenteral preparations, solutions, emulsions, suspensions, creams, ointments, and aerosols
are used in treatment of acute or chronic diseases. Now a day’s also these formulations can be
considered as primary pharmaceutical products commonly seen in the market. When such a
conventional dosage form is administered, the concentration of drug in systemic circulation
gradually rises to attain a therapeutic range in short time, and this concentration is maintained
for some time and finally decreases to sub-therapeutic value rendering the drug
pharmacologically inactive. Ideally the drug concentration should be continuously maintained
within therapeutic level. However, for drug with short half-life, it is not possible to maintain
the drug concentration within therapeutic range without frequent dosing. Frequent dosing
may lead to patient non-compliance and drug toxicity and the suitable alternative release
product.[1-8]
Pulsatile drug delivery systems (PDDS) are gaining importance in the field of
pharmaceutical technology as these systems deliver the right dose at specific time at a
specific site. A pulsatile drug release, where the drug is released rapidly after a well-defined
lag-time, could be advantageous for many drugs or therapies. A pulse has to be designed in
such a way that a complete and rapid drug release is achieved after the lag time so as to
match body’s circadian rhythms with the release of drug which increases the efficacy and
safety of drugs by proportioning their peak plasma concentrations during the 24 hours in
synchrony with biological rhythm. Pulsatile release systems can be classified in multiple-
pulse and single-pulse systems. Various techniques are available for the pulsatile delivery
like pH dependent systems, time dependent systems, etc. A popular class of single-pulse
systems is that of rupturable dosage forms. Advantages of the pulsatile drug delivery system
are reduced dose frequency; reduce side effects, drug targeting to specific site like colon and
many more. Now in market varies technologies of pulsatile drug delivery system like
Pulsincap, Diffucaps etc. are launched by pharmaceutical companies.The objective of any
drug delivery system is to provide drug in therapeutic amount to the proper site in the body to
achieve immediately and then maintain the desired drug concentration. These idealized
objectives are achieved by appropriately developed sustained release drug delivery which
also has diverse applicability and merits. The oral route has gained importance because of the
technological advances which helps to achieve zero order release rates of the drug, low cost
etc.[8-14]
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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MATERIAL
The following materials available were used as supplied by the manufacturer without further
purification or investigation.
Table 1: List of chemicals along with grades and their manufacturers
Sr.No. Drug/ Excipients Grade Gifted / Mfg. By
1 Meloxicam IP Ajanta Pharma
2. Hydroxy propyl methyl cellulose HPMC K4M,15M,K100M Colorcon Asia,Goa.
3. Dibasic calcium phosphate IP Sudeep pharma
4. Microcrystalline cellulose IP FMC
5. Sodium starch glycolate IP Ameshi drugs
6 Lake sunset yellow IP Roha chemical
7. Lake quinoline yellow IP Sensient
8. Magnesium stearate IP Nitika Phrma
9. Hydrochloric acid AR Rankem
10. Sodium hydroxide AR Rankem
11. Potassium dihydrogenphosphate AR Rankem
METHOD
Press coated floating-pulsatile release formulations:
Preparation of core tablets (CT):
All ingredients of core tablet given in Table No 6were weighed and passed through 30mesh
size. This powder was mixed thoroughly in mortar and lubricated with magnesium stearate (1
% w/w). A 200 mg powder was weighed and transferred manually in to die and compressed
by using 8 mm diameter SC punch tooling.
Table 2: Effect of Sodium starch glycolate level on Drug Release Profile from Uncoated
Tablet (CT-1 to CT-4) 8 %, 4%, 2% & without disintegrant
S.No Formulation CT1 CT2 CT3 CT4
Ingredients mg/Tab mg/Tab mg/Tab mg/Tab
1 Meloxicam 30 30 30 30
2 MCC(Avicel pH102) 110 114 116 118
3 Di calcium phosphate (DCP) 40 44 46 48
4 Sodium starch glycolate 16 8 4 0
5 Sunset yellow iron oxide 2 2 2 2
6 Magnesium stearate 2 2 2 2
F= Formulation code for CT1 - Core tablet 1 with Sodium starch glycolate 8%, CT2= Core
tablet 2 with Sodium starch glycolate 4%, CT3= Core tablet 3 with Sodium starch glycolate
2%, CT4= Core tablet 4 with Sodium starch glycolate without disintegrant.
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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Press coated tablets:
Formulation compositions of coating layer (F1 to F22) are shown in Table 7 describes
varying percentage of polymers were weighed and passed through 22 mesh sieve. The all
ingredients of coating layer were mixed in a mortar. Required weight of coating powder was
weighed and used in two steps 200 mg of the powder mixture was used for the upper and
lower shell. First half coating powder was filled into the die and CT 1 was placed in the
center of die. CT 1 was slightly pressed to fix the coating around and under the CT1 Then
remain of half coating powder was filled and compressed by using 12 mm flat faced punch
tooling.
Formulation of press coated tablets with rupturable material (EC) combined with
erodible material (Klucel EXF) in the outer shell. (Formulation F1 –F7)
Table 5 shows different ratio of rupturable material (EC) combined with erodible material
(Klucel EXF) in the outer shell. From developed formulation best formulation study for
Effect of rotational speed on lag time
Table 3: Formulation of press coated tablets with rupturable material (EC) combined with
erodible material (Klucel EXF) in the outer shell
Formulation
No.
Core
Tablet
Coating material
(200mg)
Ratio
(%)
F1 CT-1 Klucel EXF: EC N 20 100:0
F2 CT-1 Klucel EXF: EC N 20 87.5:12.5
F3 CT-1 Klucel EXF: EC N 20 75:25
F4 CT-1 Klucel EXF: EC N 20 50:50
F5 CT-1 Klucel EXF: EC N 20 25:75
F6 CT-1 Klucel EXF: EC N 20 12.5:87.5
F7 CT-1 Klucel EXF: EC N 20 0:100
Effect of rotational speed on lag time of press-coated tablet:
Effect on rotational speed on lag time of press coated tablet studied on best formulation
obtain in with rupturable material (EC) combined with erodible material (klucel EXF) inthe
outer shell
Formulation of press coated tablets with gellable material (HPC-HF) combined with
erodible material (HPC-EXF) in the outer shell (Formulation F8 –F14):
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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Table 4: Formulation of press coated tablets with gellable material (HPC-HF) combined with
erodible material (HPC-EXF) in the outer shell
Formulation
No.
Core
Tablet
Coating material
(200mg)
Ratio
(%)
F8 CT-1 Klucel EXF: Klucel HF 100:0
F9 CT-1 Klucel EXF: Klucel HF 87.5:12.5
F10 CT-1 Klucel EXF: Klucel HF 75:25
F11 CT-1 Klucel EXF: Klucel HF 50:50
F12 CT-1 Klucel EXF: Klucel HF 25:75
F13 CT-1 Klucel EXF: Klucel HF 12.5:87.5
F14 CT-1 Klucel EXF: Klucel HF 0:100
RESULT & DISCUSSION
Preformulation study:
Excipients Compatibility study:
From Preformulation study three is no physical change is observed mixture drug
andexcipients.
Table 5: Compatibility studies of Meloxicam, with different excipients
Sr.
No. Drug + Excipients
Drug: Excipients
(Ratio)
After one week
40°C/75%RH
After Two
weeks
40°C/75%RH
After Four
weeks
40°C/75%RH
1. Drug - No colour
change
No colour
change
No colour
change
2. Drug + Dicalcium
phosphate 1:5
No colour
change
No colour
change
No colour
change
3. Drug + MCC (Avicel
pH102 ) 1:5
No colour
change
No colour
change
No colour
change
4. Drug + Ethyl
cellulose 1:3
No colour
change
No colour
change
No colour
change
5. Drug + HPC-EXF 1:3 No colour
change
No colour
change
No colour
change
6. Drug + HPC-HF 1:3 No colour
change
No colour
change
No colour
change
7. Drug + Lake sunset
yellow 10:1
No colour
change
No colour
change
No colour
change
8. Drug + Titanium
dioxide 10:1
No colour
change
No colour
change
No colour
change
9. Drug + Magnesium
stearate 10:1
No colour
change
No colour
change
No colour
change
10. Drug + Sodium starch
glycolate 1:3
No colour
change
No colour
change
No colour
change
11. Drug + Talc 10:1 No colour
change
No colour
change
No colour
change
12. Drug + All excipients 5:5 No colour
change
No colour
change
No colour
change
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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Fig. 1: Fourier transformer infrared spectroscopy (FTIR) of pure drug
Fig. 2: Fourier transformer infrared spectroscopy (FTIR) of drug with polymeric mixture
Standard Calibration Curve for Meloxicam in pH 6.8 Phosphate Buffer
Meloxicam is freely soluble in pH 6.8 Phosphate Buffer. The concentrations of Meloxicam
and the corresponding absorbance values are given in Table 8. The standard curve for
Meloxicam was plotted against concentration and the calibration curve is shown in Fig.3
Table 6: Concentration versus absorbance Fig. 3: Calibration curve for the estimation of
values for the estimation of Meloxicam Meloxicam
Concentration
(µg/ml)
UV Absorbance
(Mean ± S.D)
2 0.090±0.02
4 0.170±0.03
6 0.233±0.12
8 0.314±0.21
10 0.386±0.18
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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EVALUATION OF TABLET
1. Evaluation of core tablets (CT)
Physicochemical properties of tablet:
Tables are evaluated for Weight variation, thickness. Hardness, friability and drug content
Results of physicochemical evaluation of core tablets (CT) are given in Table 6.3
Table 7: Evaluation of physical properties of formulation CT1 to CT4
Formulation
Code
Weight
Variation (mg)
n=20
Thickness
(mm) n=10
Hardness (N)
n=10
Friability
(%)
Drug content
(%) n=3
CT1 200.10±1.24 3.20±0.1 80 N ± 10N 0.21 99.58±1.65
CT2 200.15±1.11 3.20±0.1 80N ± 12N 0.11 100.25±1.98
CT3 200.24±1.27 3.20±0.1 80N ± 9 N 0.25 99.98±1.56
CT4 200.24±1.19 3.20±0.1 80 N ± 11N 0.15 100.58±2.15
In vitro Dissolution Study
In vitro dissolution test was carried out in pH 6.8 Phosphate Buffer for 60 min. Results ofin
vitro dissolution test presented in Table and Figure. In order to perform different release
kinetics; depending upon different release mechanism involved, effect of Sodium starch
glycolate level on drug release profile from uncoated tablet (Formulations CT1 toCT4) were
determined. As amount of Sodium starch glycolate level decrease from formulations CT-1 to
CT-4; the formulation containing highest amount of Sodium starch glycolate (CT-1) showed
fast disintegration and fast release because of swellable disintegrant present in it. As amount
of swellable disintegrant decrease amount of drug release decreased. Without disintegrate
Sodium starch glycolate level in formulation CT-4 showing decrease in disintegrant property.
As shown in figure 6.4significant change in release profile CT1 shows drug release initially
faster compare to CT -4 which without disintegrant.
Table 8: % Effect of Sodium starch glycolate level on Drug Release Profile fromUncoated
Tablet (CT-1-CT-4)8 %,4%, 2% & without disintegrant.in pH 6.8 Phosphate Buffer of
different core tablets formulations
Time
(min)
% Cumulative Drug Release
CT1 CT2 CT3 CT4
0 0 0 0 0
5 72.4 46.5 20.2 5.3
10 99.5 62.7 44.2 17.6
15 101.2 84.1 80.5 30.2
30 100.1 100.5 100.1 79.0
45 99.6 99.3 98.7 100.7
60 98.4 98.6 98.2 99.1
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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Fig.4: Dissolution of Meloxicam core tablet formulation with various concentration of
disintegrant Sodium starch glycolate 8 %(CT-1),4% (CT-2),2%(CT-3) & without disintegrant
(CT-4)
Disintegration of CT1 was studded in petri plate it was observed that tablet disintegrate very
fast due to higher concentration of disintegrant Sodium starch glycolate 8 %.It was
disintegrate completely within 60 Sec.
2. Effect of rupturable material (EC) combined with erodible material (Klucel EXF)in
the outer shell.
A. Physicochemical properties of tablet:
Tables are evaluated of formulation Weight variation, thickness. Hardness, friability and drug
content Results of formulation physicochemical evaluation of press coated tablets (F1 –F7)
containing rupturable material (EC) combined with erodible material (klucel EXF) in the
outer shell.
Table 9: Results of physicochemical evaluation of press coated tablets (F1 –F7)
Formulation
No.
Weight
Variation (mg)
n=20
Thickness
(mm) n=10
Hardness
(N) n=10
Friability
(%)
Drug Content
(%) n=3
F1 400.10±1.36 5.25 ± 0.04 14 ± 0.56 0.25 98.58±1.64
F2 400.15±1.42 5.30±0.02 14 ± 0.42 0.16 99.25±1.96
F3 400.24±1.56 5.12±0.02 14 ± 0.36 0.24 100.98±1.40
F4 400.24±1.19 5.26±0.02 14 ± 0.51 0.17 100.58±2.10
F5 400.10±1.20 5.62±0.04 14 ± 0.59 0.23 99.25±2.15
F6 400.24±1.64 5.40±0.05 14 ± 0.32 0.29 100.58±2.15
F7 400.10±1.80 5.36±0.03 14 ± 0.56 0.36 98.25±2.20
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3. Effect of gellable material (HPC-HF) combined with erodible material (HPCEXF) in
the outer shell
A. Physicochemical properties of tablet:
Tables are evaluated for Weight variation, thickness. Hardness, friability and drug
content.Results of physicochemical evaluation of press coated tablets (F8 –F14)containing
gellable material (HPC-HF) combined with erodible material (HPC-EXF) in the outer shell
are given in Table 6.6
Table 10: Results of physicochemical evaluation of press coated tablets (F8– F14)
Formulation
No.
Weight
Variation (mg)
n=20
Thickness
(mm)
n=10
Hardness
(N)
n=10
Friability
(%)
Drug Content
(%)
n=3
F8 401.10±1.42 5.24 ± 0.04 14 ± 0.65 0.28 99.58±1.64
F9 400.18±1.52 5.35±0.02 14 ± 0.48 0.19 100.25±1.98
F10 402.24±1.32 5.15±0.02 14 ± 0.38 0.28 101.98±1.50
F11 401.24±1.19 5.24±0.02 14 ± 0.57 0.19 99.58±2.30
F12 400.10±1.56 5.42±0.04 14 ± 0.62 0.27 100.25±2.15
F13 402.24±1.38 5.51±0.05 14 ± 0.52 0.30 99.58±2.15
F14 401.10±1.72 5.37±0.03 14 ± 0.59 0.38 99.28±1.86
Dissolution of press coated tablets
4. Effect of rupturable material (EC) combined with erodible material (klucelEXF) in
the outer shell.
By combining rupturable polymer (EC) with erodible polymer (HPC-EXF) lag time increases
with increasing weight ration of EC/HPC-EXF in formulation F8 to F14. But while using EC
alone lag time is lowest as compared to any weight ratio of EC/HPCEXF. This is only
because while combining hydrophilic HPC-EXF with EC; HPC-EXF acts as a binder too. As
tablet comes in the contact of dissolution medium HPC-EXF hydrates but as EC is
hydrophobic in nature it retards the hydration of HPC-EXF and as EC is semi permeable in
nature.
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Fig. 6: Possible scheme for drug release from the time controlled rupturing and EC/HPC-
EXF mixture press coated tablet
Dissolution medium penetrates faster in EC coated tablet compared to along with HPCEXF.
While HPC-EXF forms a compacts with EC and water would not penetrate faster as
compared to EC outer coating shell.
Thus due to both concomitance synergistic effect lag time is increase with increasing weight
ratio of EC/HPC-EXF. As HPC-EXF made a compact with EC; because of different weight
ratio of EC/HPC-EXF, outer shell may get eroded first and then when sufficient internal
pressure built because of AC-Di-Sol present in formulation F1 to F5 outer shell broke into
two halves and cause a stage of rapid drug release. Obviously, the period of lag time was
different and dependent on the weight ratio of EC/HPC-EXF.
The order of the time lag changed according to the weight ratio of EC/HPC-EXF mixture as
follows: (100: 0)-3hr,( 87.5 : 12.5)-6 hr, (75 : 25)-7 hr,(50 : 50)-7.5 hr, (25 : 75)-8.5 hr (12.5:
87.5)-7 hr, (0: 100)-5 hr The lag time and drug release profile of Meloxicam from dry-coated
tablets using different weight ratio of EC/HPC-EXF mixture are given in table and figure.
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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Table 11: Effect of rupturable material (EC) combined with erodible material (Klucel EXF)
in the outer shell on dissolution
Tim
e
(Hr)
% Drug Release
F1 F2 F3 F4 F5 F6 F7
0 0 0 0 0 0 0 0
1 10.5±1.34 2.6±1.74 2.1±1.54 1.5±1.57 1.9±1.34 2.5±1.25 2.9±1.25
2 18.8±1.46 3.4±1.89 4.5±1.89 2.8±1.64 2.5±1.84 3.6±2.4 3.7±1.29
3 100.82±1.6
2
4.2±1.25 5.7±1.64 3.7±1.44 3.6±1.35 4.8±1.58 5.4±1.04
4 99.85±1.27 5.9±1.61 6.8±1.48 6.8±1.32 6.2±1.49 5.9±1.34 6.4±1.37
5 -- 6.7±1.39 10.8±1.62 9.4±2.46 9.9±1.38 9.7±1.89 98.47±2.9
8
6 -- 99.70±1.66 12.4±1.72 11.6±1.34 11.7±1.47 13.6±1.67 100.22±1.
4
6.5 -- 100.25±2.3
2
15.9±1.62 12.5±1.78 13.5±1.89 15.4±1.23 --
7 -- -- 98.32±2.9
8
16.5±1.34 15.9±1.67 18.2±1.25 --
7.5 -- -- 100.08±1.
2
98.82±1.7
8
16.2±1.26 99.26±1.32 --
8 -- -- -- 99.99±2.3
6
18.4±1.64 101.02±1.6
2
--
8.5 -- -- -- -- 100.56±1.2
3
-- --
9 -- -- -- -- 98.25±1.59 -- --
Fig. 7: Drug release profile of Meloxicam from dry-coated tablets using different weight ratio
of EC/HPC-EXF
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Dissolution of press coated tablets: Effect of gellable material (HPC-HF) combined with
erodible material (HPC EXF) in the outer shell. (Formulation F8 to F 14) on drug
release.
Formulation F8 to F14 and increase in lag time and with increase in weight ration of HPC-
HF/HPC-EXF. When HPC-HF combines with HPC-EXF in this ratio, the final viscosity of
this mixture increase hydroxyl propyl cellulose HPC-EXF. When it is comes in contact
dissolution medium it forms a gel formation take place. Due to higher concentration of HPC-
EXF this gel formation take place which is not so tight but it eroded and gelled
simultaneously. Formulation F8 shows the drug release by bursting effect as pressure
generate in core tablet is enough to separate two halves or break the coating layer after some
erosion take place of HPC due to specific release profile of 4 hrs. When core tablet present in
formulation hydrates by dissolution medium due to sodium starch glycolate present in it in
presence of microcrystalline cellulose it swells and give burst profile. At initial time point
slow release of drug due to medium required time to contact to core tablet .it hydrates the
core due to tight gelled structure of shell some drug is eject out by diffusion mechanism and
when internal pressure is enough to break the coating layer rapid drug release was observed.
The lag time increase as increasing concentration of viscosity HPC because the erosion of
polymer required time due to which release of drug delayed profile observed. Desired drug
release is achived by using gellable and erodible polymers and drug profile depend on
concentration of polymer and grade The order of the time lag changed according to the
weight ratio of EC/HPC-EXF mixture as follows: (100: 0)-4hr,( 87.5 : 12.5)-6 hr, (75 : 25)-
6.5 hr, (50 : 50)-7.5hr, (25 : 75)- 7.5hr (12.5: 87.5)-8hr, (0: 100)-5hr. The lag time and drug
release profile of Meloxicam from dry-coated tablets using different weight ratio of HPC-
HF/HPC-EXF mixture are given in Table & Figure.
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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Table 12: Effect of gellable material (HPC-HF) combined with erodible material(HPC-
EXF) in the outer shell. (Formulation F8 to F 14) on drug release
Time
(Hr)
% Drug Release
F8 F9 F10 F11 F12 F13 F14
0 0 0 0 0 0 0 0
1 9.8±1.86 4.5±1.25 3.5±1.48 2.9±2.84 1.8±2.78 2.4±1.45 3.6±1.64
2 12.4±1.94 6.4±1.62 5.8±1.56 4.7±1.89 2.6±1.67 3.9±2.64 5.4±1.84
3 16.6±1.73 8.5±1.85 7.4±1.62 5.9±1.65 5.4±1.73 5.4±1.84 6.9±1.95
4 102.25±1.2
4 10.2±1.24 8.9±1.84 6.8±1.58 6.7±1.54 6.8±1.62 8.2±2.08
5 100±1.22 12.6±1.68 9.4±2.43 8.2±1.84 8.2±1.98 8.4±1.07 98.6±1.4
6 -- 98.00±2.6
7 10.6±2.01 11.2±1.47 9.7±2.01 10.5±1.73
100.44±1.
5
6.5 -- 99.96±2.0
1 12.4±2.12 13.6±1.68 10.5±2.34 12.6±1.73 --
7 -- -- 101.2±2.0
5 99.7±1.59 11.7±1.73
101.2±1.8
8 --
7.5 -- -- 99.85±2.3
5
100.32±2.
47
100.54±1.
59
100.25±2.
57 --
8
99.90±1.7
3
Fig. 8: Effect of gellable material (HPC-HF) combined with erodible material (HPC-EXF) in
the outer shell. (Formulation F8 to F 14) on drug release
STABILITY STUDY:
Effect of rupturable material (EC) combined with erodible material (klucelEXF) in the outer
shell. (Formulation F2) and gellable material (HPC-HF) combined with erodible material
(HPC-EXF) in the outer shell (Formulation F9) on drug release
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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Optimized formulations were studied for stability study at 400C /75% RH for six month.They
are packed in alu pouch and charged for stability study. Then product evaluated fordrug
content and in vitro dissolution test shown in Table No 6.9 and in Figure6.9
Table 13: % Cumulative release of Meloxicam for in phosphate buffer pH6.8 of
Formulations. (F2 and F 9)
Test Analytical Results
Dissolution % Cumulative Release
Time (Min) F2 F9
40°C/75% RH 30°C/65% RH 30°C/65% RH 40°C/75% RH
1 1.2±1.85 1.6±2.23 1.5±2.42 1.7±2.21
2 2.6±1.94 2.9±2.54 3.2±1.98 3.1±2.25
3 4.2±2.52 4.7±2.62 4.9±2.01 5.2±1.46
4 5.9±1.96 6.2±2.08 5.8±2.52 6.1±1.98
5 6.2±2.40 6.8±1.94 6.4±2.64 6.9±2.45
6 98.25±2.66 99.20±1.56 100.24±1.68 98.20±2.54
6.5 99.80±2.45 100.22±2.58 99.9±2.69 99.22±1.85
Drug Content 99.54±2.58 101±1.96 100.21±2.21 99.26±1.65
Fig. 9: % Cumulative release of Meloxicam for in phosphate buffer pH6.8 of formulations.
(F2 and F9)
From above observation it was conclude that drug release profile and drug content there was
no change. It passes 6 M 400C /75% RH.
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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CONCLUSION
The objective of the present work was to develop a pulse type profile of formulation of
Meloxicam by using compression coating technique The formulation is administered at bed-
time provides nocturnal recovery of gastric acid secretion by releasing drug from formulation
in time controlled manner. The following conclusions can be drawn on the basis of above
formulation development studies: The use of hydrophilic polymer with erodible and gellable
properties in the dry coating development of pulse type drug release achieved .Compression
coating tablets utilizing Hydroxypropylcellulose in the outer shell gives timed release profile.
Drug was released burst when complete erosion of shell when low viscosity grade (erodible
polymer) HPC was used. By combining different HPC viscosity grades it is possible to obtain
a time-lags of 3 to 9 hrs with different core composition with different release kinetics. Effect
of rupturable material (EC) combined with erodible material (Klucel EXF) in the outer shell
was studied it was observed using EC alone lag time is lowest as compared to any weight
ratio of EC/HPC-EXF. This is only because while combining hydrophilic HPC-EXF with
EC; HPC-EXF acts as a binder too. As tablet comes in the contact of dissolution medium
HPC-EXF hydrates but as EC is hydrophobic in nature it retards the hydration of HPC-EXF
and as EC is semipermeable in nature. F2 formulation was best formulation with ratio Klucel
EXF: EC N 20 (87.5: 12.5) showed 6 Hr release. It was studied for increasing paddle
rotational speed. It was observed decrease in lag time observed with increasing paddle
rotational speed. Effect of gellable material (HPC-HF) combined with erodible material
(HPCEXF)in the outer shell was studied it was observed drug retardation increased and with
increase in concentration HPC-HF/HPC-EXF. When HPC-HF combines with HPC-EXF in
this ratio, the final viscosity of this mixture increase that of HPC-EXF alone. Upon contact
with dissolution medium there is formation of gel which is due to increase concentration
HPC-EXF.it is eroded and gelled simultaneously F9 formulations were best formulation with
ratio HPCEXF/ HPC-HF (87.5: 12.5) showed 6 Hr release. From above present work it can
be concluded that, press coating of drug is necessary for providing pulsatile release profile.
The polymer coating level and quantity of polymer played a main role for providing pulsatile
release pattern. The optimized formulation F2 passes 3 M400 C /75% RH in Alu pouch. They
are suitable formulation for pulsatile drug delivery of Meloxicam.
Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.
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