formulation and evaluation of pulsatile...

Anjali B & Srinivas N. Int J Trends in Pharm & Life Sci. 2015: 1(1); 1-17.

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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


www.ijtpls.com

Volume: 1, Issue: 1

mailto:[email protected]


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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]


3

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.


4

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




F6 CT-1 Klucel EXF: EC N 20 12.5:87.5


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):


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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




F13 CT-1 Klucel EXF: Klucel HF 12.5:87.5


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


6

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


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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


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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.


10

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.


11

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


12

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.


13

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


14

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.


15

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.


16

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formulation and evaluation of pulsatile...

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