FORMULATION AND EVALUATION OF LANSOPROZOLE ......Modified release dosage form may be classified as...

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Saibabu et al. European Journal of Pharmaceutical and Medical Research

753

FORMULATION AND EVALUATION OF LANSOPROZOLE DELAY RELEASE

PELLETS

Ch. Saibabu*, K. Harikrishna, S. K. Karishma, G. Praveen Kumar, N. Yajjari and Y. Sri Sruthi

Department of Pharmaceutics, M.L. College of Pharmacy, Singarayakinda, A.P-523101.

Article Received on 21/02/2020 Article Revised on 11/03/2020 Article Accepted on 01/04/2020

INTRODUCTION

Drug Delivery System[1]

The treatment of acute diseases or chronic illness has

been achieved by delivery of drugs to the patients for

many years. These drug delivery systems include tablets,

injectables, suspensions, creams, ointments, liquids and

aerosols. Today these conventional drug delivery

systems are widely used. The term drug delivery can be

defined as techniques that are used to get the therapeutic

agents inside the human body. Modified release DDS

include systems with pH-dependent, extended, delayed or

pulsed drug release. Sustained, extended or prolonged

release drug delivery systems are terms used

synonymously to describe this group of controlled drug

delivery.

Classification Modified release dosage form may be classified as

Extended release.

Sustained release.

Controlled release.

Site-specific and receptor targeting.

Delayed release.

Delayed Release Solid Oral Dosage Forms[7]

The correct selection and balance of excipients and

processes in solid dosage formulations are designed

either for improving the micromeritic or macromeritic

properties of materials during manufacture and/or for

providing a desired drug delivery system. The most

commonly used pharmaceutical delayed release solid

oral dosage forms today include tablets, capsules,

granules and pellets.

Lansoprazole

Lansoprazole is a proton pump inhibitor (PPI) which

inactivates the final step in the gastric acid secretion

pathway in gastric parietal cells in a dose-dependent

manner. ... Lansoprazole comes under the BCS II

SJIF Impact Factor 6.222

Research Article

ISSN 2394-3211

EJPMR

EUROPEAN JOURNAL OF PHARMACEUTICAL

AND MEDICAL RESEARCH

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ejpmr, 2020,7(4), 753-766

ABSTRACT

The work was carried out to delay the release of Lansoprazole by using enteric polymer Methacrylic acid

copolymer (type C). The study includes preformulation of drug and excipients, formulation and evaluation, release

kinetics and stability studies of capsules. Drug Loading was given to sugarsheres by using different binders i.e.,

Klucel- LF and L- HPC with different concentrations. The amount of drug bound to sugarsheres increases with an

increased concentration of HPC(L-type) (17.5% and 22%). But at high concentration of HPC (22%), lumps were

observed. Finally, 17.5% w/w HPC was optimized as binder for drug coating. Sub coating was given to drug

loaded pellets to avoid direct contact with enteric coating. Sub coating was given with HPC and Corn starch

combination at an average weight build-up of 6.1% w/w of sub coated pellets. Enteric coating was given to

Lansoprazole pellets by Methacrylic acid copolymer type C (30% aqueous dispersion). Enteric coating was

optimized at an average weight build-up of 53% w/w of enteric coated pellets and release profile was compared

with Innovator. In enteric coating, plasticizer plays major role in film formation of pellets. Among TEC and PEG

6000, TEC was found to have good film forming capacity. Plasticizer concentration was optimized at 20% of dry

polymer weight. Enteric coated pellets were evaluated for assay, acid resistance and dissolution; E6 enteric coated

pellets were found to be optimized and were filled into capsules. These capsules were evaluated and the results

were found to be more similar with innovator. Different kinetic models were applied to optimized enteric coated

formulation (E6) and observed that it follows zero order kinetics with Higuchi diffusion mechanism. Stability

studies were conducted at 40ºC / 75% RH (accelerated stability testing) for 3 months. Assay, acid resistance,

dissolution release profile of optimized enteric coated formulation (E6) complies with Innovator and was found to

be stable.

KEYWORDS: Lansoprazole, Preformulation, enteric coating, delay released pellets.

*Corresponding Author: Ch. Saibabu

Department of Pharmaceutics, M.L. College of Pharmacy, Singarayakinda, A.P-523101.

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classification drug which has poor aqueous solubility &

bioavailability.

Figure 1: Strucute of lansoprazole.

Experimental work

Materials

All Material were procured like Lansoprazole from

Hetero Drugs, Sugar Spheres (#20/#25) From Werner, L-

Hydroxypropyl Cellulose From Aqualon, Hydroxypropyl

Cellulose From Aqualon, Magnesium Carbonate From

Merck, Titanium Dioxide From Kronos, Methacrylic

Acid Copolymer Type C From Degussa, Triethyl Citrate

From Morflex, Polyethylene Glycol 6000 From Clariant,

Corn Starch From Basf, Sodium Lauryl Sulphate From

Merck, Mannitol From Spi Pharma, Polysorbate From 80

Crillet 4, Talc From Luzenac Pharma ltd Etc.., All

instruments used in the project Electronic Single pan

balance from Sartorius Mechanical Sifter with Sieve #24,

30, 50, 60, 80 and 100 Mesh # 12, 14, 16, 18, 40,60,100

from Retsec, Tapped density tester USP from Electro

lab, Analytical Sieve Shaker from Retsec Blender Rimek

Mechanical stirrer from Remi motors Bombay, Fluidized

Bed Dryer from Retch, Fluidized Bed processor(Wurster

coater) Plam glatt, from Japan, Capacity: 1.5 kg,

Disintegration Test Apparatus USP from Electro lab,

Moisture analyser from Sartorius, Stability chambers

from Thermo lab, pH meter from Eutech Cyberscan-100,

Dissolution Test Apparatus USP from Electro lab, HPLC

from Waters.

Methods

S.NO Name of ingredients D1(mg) D2(mg) D3(mg) D4(mg) D5(mg) D6(mg) 1. Lansoprazole USP 30 30 30 30 30 30 2. Sugar spheres(#20,25) USP-NF 108.8 110 110 110 135 150 3 Sucrose 19.8 19.8 19.8 19.8 19.8 19.8 4. Mgco3 light 22.4 22.4 22.4 - - - 5. Mgco3 Heavy - - - 22.4 22.4 22.4 6. Corn starch 20 5 20 5 5 5 7. L-HPC(LH-11) 20.7 30 20.7 - - - 8. L-HPC(LH-31) - - - 30 24 24 9. SLS - - 8.7 8.7 8.7 8.7 10. HPC-L(Nisso HPC-L) - - - - - 4.5 11. HPC-L(Klucel-LF) - - - - 6 - 12. Purified water Q.S Q.S Q.S Q.S Q.S Q.S 13. Total weight 221.7 217.2 225.9 225.9 250.9 264.4

Formulation trails

Sub Coating

Table 1: Formulation for Sub coating.

S. No Sub coating D5S1 D5S2 D5S3 D5S4 1 Drug pellets 250.9 250.9 250.9 250.9 2 Pharma grade Sugar 10 30 30 30 3 Corn Starch 5 5 5 5 4 L-HPC(LH11) 5 15 15 10 5 HPC(L Type) - - 2

6 HPC(Nisso HPC) -

- -

7. Purified water Q.S Q.S Q.S Q.S

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Enteric coating

Table 2: Formulation for Enteric coating.

S.No. ENTERIC COATING E1 E2 E3 E4 E5 E6 E7 1 Sub coated pellets S3 302.9 302.9 302.9 302.9 302.9 302.9 302.9 2 Eudragit L30D55 24.75 24.85 25.25 37.86 37.86 42.9 47.98 4 Triethyl citrate 2.475 2.485 2.525 3.786 - 4.29 4.798 5 Polyethylene glycol - - - - 3.786 - - 6 Talc 1.7325 1.7395 1.7675 2.6502 2.6502 3.003 3.3586 7 Polysorbate 80 0.495 0.497 0.505 0.7572 0.7572 0.858 0.9596 8 Purified water q.s q.s q.s q.s q.s q.s q.s

Total 332.35 332.47 332.94 347.95 347.5 353.95 359.96

1. PREFORMULATION STUDIES Preformulation study is an investigation of physical and

chemical properties of a drug substance alone and when

combined with excipients. It is the first step in the

rationale development of dosage form.

Description

Lansoprazole is an off-white to cream colored crystalline

hygroscopic powder.

2. KINETIC ANALYSIS OF IN-VITRO RELEASE

RATES OF DELAYED RELEASE CAPSULES OF

LANSOPRAZOLE.

3. EVALUATION OF DELAYED RELEASE

FORMULATIONS AND COMPARISION WITH

INNOVATOR

Delayed release formulations include enteric coated

pellets and capsule formulations.

Assay Acid resistance Drug Release Dissolution (acid stage followed by buffer stage) Kinetic studies of Innovator and Optimized

formulation

Stability studies of Optimized formulation

Assay (by HPLC)

Procedure Weigh and mixed the contents of not less than 20

capsules. Accurately weigh pellets equivalent to about

20mg of Lansoprazole were transferred into 100ml

volumetric flask. About 50ml of diluents was added to

the flask and was sonicated for about 15min and cool,

diluted to the required volume with diluents like

acetonitrile and mixed. A portion of the solution is

filtered through 0.45 µm filter and filtrate was analyzed

by HPLC, by preparing the standard for the same.

Preparation of Diluent A (0.1N Methanolic NaOH)

4gms of NaOH was weighed and transferred into a beaker containing 100ml of water and sonicated to

dissolve.

This solution was transferred into a 1000ml of volumetric flask and diluted to volume with

methanol.

Preparation of Diluent B

Prepared a degassed mixture of water, acetonitrile and triethlyamine in ratio 600:400:10v/v and

adjusted the pH to 10.0 ± 0.05 with ortho phosphoric

acid.

Preparation of Buffer (pH 7.4)

10ml of Triethyl amine was transferred into a beaker containing 1000ml of water and adjusted the pH to

7.4 ± 0.05 with ortho phosphoric acid.

Preparation of Mobile Phase

Prepared a degassed mixture of water, acetonitrile and triethlyamine in ratio 600:400:10 v/v and


acid.

Preparation of Standard Solution

About 30mg of Lansoprazole working standard was accurately weighed and transferred into 100ml

volumetric flask. About 60ml of diluents was added

and sonicated to dissolve. Diluted to volume with

diluents acetonitrile.

4ml of above solution was transferred into 100ml volumetric flask and diluted to volume with diluents

B and mixed.

Preparation of Sample Solution

500ml of 0.1N HCl was transferred into each vessel and allowed the medium to temperature 37±0.5

0C.

One capsule in each vessel was placed and operated at 75 rpm for 1 hour.

At the end of 1st hour 0.1N HCl was discarded from each vessel and the pellets were collected in 100ml

of volumetric flask and dried.

Entire quantity of pellets of each vessel were transferred immediately into dry individual 100ml

volumetric flasks with aid of suitable filter or mesh

and ensure complete transfer of pellets to the

volumetric flask.

About 60ml of diluent was added and sonicated for 20 minutes with shaking until the pellets are

completely dissolved.

Diluted to volume with diluents acetonitrile.

A portion of solution was filtered through 0.45μ filter and first few ml of filtrate was discarded

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4ml of above solution was transferred into 100ml volumetric flask and diluted to volume with diluent

B.

A portion of solution was filtered through 0.45μ filter and first few ml of filtrate was discarded.

Procedure

10 μl of mobile phase, standard solution (5 times) and

sample solution were separately injected into HPLC. The

chromatograms were recorded and peak responses were

measured.

Evaluation of system suitability parameters

Column efficiency as determined for peak from 5 replicate injections of standard solution was NLT

2000 theoretical plates and tailing factor for same

peak was NMT 2.

The % RSD for five replicate injections of standard solution was NMT 2.

Retention time was about 8 min. Calculation

AT=Area of Lansoprazole peak in sample solution

AS=Average Area of Lansoprazole peak from 5 replicate

injection of standard solution

WS=Weight of Lansoprazole working standard in mg

WT=Weight of Test in mg

P=Purity of Lansoprazole working standard

Chromatographic Conditions

Column : Zorax SBC18, 4.6 X 250 mm, 5μm

Flow Rate : 1.0ml/min

Wave length : 281nm

Injection Volume : 10μl

Column temp : Ambient

Run time : 15 minutes.

Dissolution Parameters

Medium : 0.1N HCl

Volume : 500ml

Apparatus : USP-II, paddle

Speed : 75 rpm

Temp : 37±0.50C

Sampling points : 2 hrs

Preparation of 0.1 N HCl

8.5ml of HCl was diluted to 1000ml with water.




Wave length : 281nm



Run time : 15 minutes

Preparation of Diluent A (0.1N Methanolic NaOH)

2gms of NaOH was weighed and transferred into a 500ml of volumetric flask and diluted to volume

with water.

Preparation of Diluent B

Prepared a degassed mixture of water, acetonitrile and triethlyamine in ratio 600:400:10 v/v and


acid.

Preparation of Mobile Phase

Prepared a degassed mixture of water, acetonitrile and

triethlyamine in ratio 600:400:10v/v and adjusted the pH

to 7.0 ± 0.05 with ortho phosphoric acid.



volumetric flask. About 60ml of diluent was added

and sonicated to dissolve. Diluted to volume with

diluents acetonitrile.

4ml of above solution was transferred into 100ml volumetric flask and diluted to volume with diluents

B and mixed.


500ml of 0.1N HCl was transferred into each vessel and allowed the medium to temperature 37±0.5

0C.

One capsule in each vessel was placed and operated at 75 rpm for 1 hour.

At the end of 1st hour 0.1N HCl was discarded from each vessel and the pellets were collected in 100ml

of volumetric flask and dried.

Entire quantity of pellets of each vessel were transferred immediately into dry individual 100ml

volumetric flasks with aid of suitable filter or mesh

and ensure complete transfer of pellets to the

volumetric flask.

About 60ml of diluent was added and sonicated for 20 minutes with shaking until the pellets are

completely dissolved.

Diluted to volume with diluents acetonitrile.

A portion of solution was filtered through 0.45μ filter and first few ml of filtrate was discarded

4ml of above solution was transferred into 100ml volumetric flask and diluted to volume with diluent

B.

A portion of solution was filtered through 0.45μ filter and first few ml of filtrate was discarded.

Procedure

10 μl of mobile phase, standard solution (5 times) and

sample solution were separately injected into HPLC. The

chromatograms were recorded and peak responses were

measured.

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Column efficiency as determined for peak from 5 replicate injections of standard solution was NLT


peak was NMT 2.

The % RSD for five replicate injections of standard solution was NMT 2.

Retention time was about 8 min.

Calculation


AS=Average Area of Lansoprazole peak from 5 replicate





Drug Release (acid stage)

The drug release was calculated by using the following formula:

% Labelled amount of Lansoprazole dissolved in 0.1N HCL

Dissolution Prepared drug loaded pellets of Lansoprazole were taken

evaluated for in vitro drug release. Each formulation of

pellets were filled in capsules, equivalent to 30 mg of

Lansoprazole.

In vitro Drug Release

In vitro drug release of the samples was carried out using

type-II dissolution apparatus (paddle type). The

dissolution medium, 500ml of 0.1N HCL was placed into

the dissolution flask maintaining the temperature of

37±0.5ºC and rpm of 50, and drug was not released and

it is controlled and then carry out the studies in pH6.8

Phosphate buffer for one hour. Six capsules were taken,

one in each vessel for the study. 10ml of sample solution

were withdrawn after 10,20,30,45 and 60 minutes from

each vessel and replace with equal volume of fresh

dissolution medium. The samples were filtered through

0.45µm filter and 5ml from each collected samples were

taken into tubes containing 1ml of 0.25 N NaOH

solution. The samples were analyzed by HPLC by

preparing the standard at the same time and results were

reported.

(Enteric coating stage and capsules)

Acid stage (Dissolution): NMT 10% of Lansoprazole

dissolved in 1hour (USP).

1. Dissolution (Acid stage)


Medium : 0.1N HCl

Volume : 500ml

Apparatus : USP-II, paddle

Speed : 75 rpm

Temp : 37±0.50C

Sampling points : 1 hr

Dissolution (Buffer stage)


Medium : pH 6.8 sodium phosphate buffer

Volume : 900ml

Apparatus : USP-II (paddle)

Speed : 75 rpm

Temp : 37±0.50C

Sampling points : 10,20,30,45 and 60 min

Preparation of Buffer concentrate

65.4g of sodium dihydrogen phosphate,28.2g of sodium hydroxide,1.2 g SLS was weighed and

transferred into a beaker containing 1000ml of water

and sonicated to dissolve.

Adjust pH to 6.8 ± 0.05 with NAOH or Ortho phosphoric acid.

Preparation of phosphate buffer (pH 6.8) blank

475 ml of 0.1N HCL and 425 ml of buffer concentrate was weighed, transferred into 1000ml of

volumetric flask and diluted to volume with sodium

hydroxide or O-phosphoric acid.

Preparation of 0.25 N NaOH

1g of NaOH pellets was weighed and transferred into a 100ml volumetric flask.

Dissolved in and diluted to volume with water.




Wave length : 281nm



Run time : 15 minutes



volumetric flask.

About 60ml of diluent was added and sonicated to dissolve. Dilute to volume with methanol.

5ml of above solution was transferred into 100ml volumetric flask and dilute to volume with Ph 6.8

sodium phosphate buffer and mixed.

5ml of above solution was transferred immediately into test tube containing 1ml of 0.25N NaOH

solution.

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Proceed as directed under acid stage with a new set of

sample from the same batch. After 1 hr in 0.1N HCl was

discarded and transferred into 1000ml of Sodium

Phosphate buffer, pH 6.8 and run at 75 rpm for specified

time. 10ml of samples were withdrawn from each

dissolution vessel. The sample was filtered through

0.45μm membrane filter and first few ml of the filtrate

was discarded. 5ml of the filtered sample solution was

immediately transferred into test tubes containing 1ml of

0.25N NaOH in a test tube.

Same procedure was followed as directed above for

release profile by maintaining the sink conditions.

Procedure: 10 μl of dissolution medium, standard

solution (5 times) and sample solution was separately

injected into HPLC. Record the chromatograms and peak

responses were measured.


The Column efficiency as determined for peak for 5 replicate injections of standard solution was NLT


peak was NMT 2.

The % RSD of peak areas of the peak from 5 replicate injections of standard solution was NMT 2.

The Retention time was about 8 min.

Calculation


AS=Average area of Lansoprazole peak from 5 replicate





Correction factor

The correction factor (CFn) was calculated at each time

point by using the formula

Dn x 10

C Fn = 1000

Dn = %labelled amount of Lansoprazole at respective

time point.

Calculation for corrected results

For 10 minute = D10

20 minute = D20+CF10

30 minute = D30+ CF20 + CF10

45 minute = D45+CF30+CF20+ CF10

60 minute = D60+CF45+CF30+CF20+ CF10

Evaluation of Capsules and comparision of Capsules

with Innovator

Capsules were evaluated for parameters like

disintegration time, content uniformity, assay, acid

resistance and dissolution which were compared with

innovator.

Kinetic studies of Innovator and Optimized

formulation

Kinetic studies were conducted for Innovator and

Optimized formulation. Zero order plot, first order plot

and Higuchi plots were plotted for Innovator and

Optimized formulation, based on the regression

coefficient values obtained kinetics of Innovator and

Optimized formulation were studied.

Stability studies for Optimized Formulation

Stability studies were conducted for the optimized

enteric coated formulation at 40ºc / 75% RH for about 3

months in stability chamber (Thermo lab). Samples were

analyzed for assay, dissolution at the end of 1st, 2

nd and

3rd

month.

RESULTS

PRE FORMULATION

Table 3: API characterization.

S. No. TEST SPECIFICATION RESULT

1 Description An off-white to cream colored

crystalline hygroscopic powder

An off-white to cream colored

crystalline hygroscopic powder

2 Solubility Soluble in water and slightly soluble

in methanol Complies

3 LOD 1.83 % w/w

4

Bulk density

True density

Haussner’s Ratio

Carr’s/Compressibility Index (%)

0.19-0.24 gm/ml

0.25-0.31 gm/ml

1.26-1.34

21-25

0.808 gm/ml

0.9 gm/ml

1.28

10.2%

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Drug Excipients compatibility study

The objective of the study was to determine the

compatibility of Lansoprazole with commonly employed

excipients.

The physical compatibility of Lansoprazole as a drug

substance with various excipients was carried out with an

aim to select suitable excipients for a stable and robust

formulation. A blend of the drug with the excipients in

the suitable ratio 1:5 was filled in double lined polybags

and exposed to 40°C/ 75% RH. The same blend was

filled in glass vials and exposed to 60°C.they were

observed for any physical change against control samples

kept at refrigerated condition of 2-8°C.

Physical observation

Physical observation of sample was done every week for

any color change or lumps formation and flow, the

results of the physical observation were shown in the

table.

Table 4: Drug Excipients compatibility study results.

S. No. Composition Details

Observations

Storage Condition / Duration

Initial 40

0C/ 75%RH

1M 2M 3M

1 API alone NCC NCC NCC NCC

2 API + Sugar spheres (#20/#25) USP NCC NCC NCC NCC

3 API + L-HPC(LH31) NCC NCC NCC NCC

4 API + Sucrose NCC NCC NCC NCC

5 API + HPC(L-type) NCC NCC NCC NCC

6 API + Magnesium carbonate NCC NCC NCC NCC

7 API + sodium laurly sulphate NCC NCC NCC NCC

8 API + Methacrylic acid copolymer type C NCC NCC NCC NCC

9 API + TEC NCC NCC NCC NCC

10 API + Polysorbate 80 NCC NCC NCC NCC

11 API + Talc NCC NCC NCC NCC

12 API + Corn starch NCC NCC NCC NCC

13 API + Titanium dioxide NCC NCC NCC NCC

EVALUATION OF ENTERIC COATED PELLETS

The following results were compared with the Innovator.

Assay

Table 5: Assay of enteric coated pellets.

% labelled amount of Lansoprazole

INNOVATOR E1 E2 E3 E4 E5 E6 E7

99.6 93 95 98 98.5 97.8 99.2 99.1

Acid resistence

Table 6: Acid resistance of enteric coated pellets.

% labelled amount of Lansoprazole retained in acid

INNOVATOR E1 E2 E3 E4 E5 E6 E7

99.3 80 80 87 93.1 91.5 98.7 99.0

Table 7: Drug release in acid stage.

% labelled amount of Lansoprazole released in acid

Time(hr) INNOVATOR E1 E2 E3 E4 E5 E6 E7 After 1 hr 0.7 13 15 11 5.4 6.4 0.5 0.1

Dissolution

Acid stage: 0.1 N HCl, 300ml, paddle, 100rpm, 120

minutes.

Buffer stage: pH 6.8 phosphate buffer, 1000ml, paddle,

100rpm,

Sampling points 10, 20, 30, 45 and 60 minutes.

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Table 8: Dissolution profile of enteric coated pellets with innovator.

Time(min) Innovator E1 E2 E3 E4 E5 E6 E7

(% labelled amount dissolved in buffer)

10 65 75 77 73 65 73 59 51 20 74 79 79 82 78 87 72 75 30 78 80 80 88 85 92 89 85 45 84 80 80 86 93 90 90 90 60 88 82 82 86 92 90 96 96

Table 9: Percent Drug Release from various Formulations.

Time (Minutes)

Percent drug released E1 E2 E3 E4 E5 E6 E7

10 75 77 73 65 73 59 51 20 79 79 82 78 87 72 75 30 80 80 88 85 92 89 85 45 80 80 86 93 90 90 90 60 82 82 86 92 90 96 96

Table 10: Drug Release Kinetic Parameters of Different Formulations.

S.NO Formula Zero order First order Higuchi Peppas

K0 R K1 R KH R n R 1 E1 0.90 0.426 0.02 0.57 0.94 0.72 0.612 0.99 2 E2 0.93 0.410 0.02 0.47 0.93 0.7 0.61 0.98 3 E3 1.05 0.47 0.027 0.58 1.03 0.76 0.613 0.994 4 E4 1.24 0.62 0.062 0.82 1.13 0.83 0.62 0.99 5 E5 1.12 0.48 0.032 0.82 1.24 0.94 0.61 0.99 6 E6 1.43 0.72 0.073 0.82 1.24 0.94 0.6 0.98 7 E7 1.44 0.74 0.041 0.87 1.23 0.93 0.52 0.94

Fig. 2: Drug Release Profiles of Enteric coated Formulations, E1 to E4.

Fig. 3: First order plot of drug release from various Enteric coated formulations, E1-E4.

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Fig. 4: Higuchi plot of drug release from various Enteric coated formulations, E1-E4.

Fig. 5: Zero order plot of drug release from Enteric coated formulations, E5 to E7.

Fig. 6: First order plot of drug release from Enteric coated Formulations E5 to E7.

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Fig. 7: Higuchi plot of drug release from enteric coated formulations E5-E7.

EVALUATION OF INNOVATOR CAPSULE

(PREVACID)

EVALUATION STUDIES OF CAPSULES

Enteric coating pellets of formulation E7 were filled into

capsules. Evaluation tests were performed for capsules.

Then the following parameters were compared with

Innovator for evaluation.

Evaluation of capsule formulation (Table No 26)

Parameters Capsule formulation Disintegration time (sec) 45 Assay (%) 99.0 Acid resistance (%) 99.3 Drug Release (%) 0.7

Comparative in vitro dissolution of Innovator and

capsule formulations

Acid stage: 0.1 N HCl, 500ml, paddle, 75rpm, 120

minutes.

Buffer stage: pH 6.8 phosphate buffer, 900ml, paddle,

75rpm,

Sampling points 10, 20, 30, 45 and 60 minutes.

Table 11: Dissolution of innovator and capsule formulation (Table No 27).

Time(min) Innovator Capsule formulation

% Drug dissolved

10 65 51

20 74 75

30 78 80

45 84 86

60 88 90

Figure 8: Comparison of drug release for innovator with capsule.

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Surface morphology study of Enteric coated pellets

Surface Morphology of Enteric Coated pellets were determined by SEM analysis.

Figure 10: SEM image of optimised formulation.

Table 12: OPTIMIZED FORMULATION.

S. No. INGREDIENTS mg/unit

I DRUG LOADING (D4)

1 sugar spheres (#20/#25) 140

2 Lansoprazole 30

3 Sucrose 19.8

4 Magnesium carbonate heavy 22.4

5 Corn starch 5

6 L-HPC (LH31) 30

7 HPC(L-type) 1

8 SLS 8.6

Total 248.2

Drug coated (%) 99.5

II SUB COATING (S3)

12 Drug loaded pellets 248.2

13 Pharma grade Sugar 17

14 Corn Starch 5

15 L-HPC(LH31) 8

16 HPC(L Type) 2

Total 280.2

III ENTERIC COATING(E6)

17 Subcoated pellets 280.2

18 Eudragit L30D55 37.94

19 Triethyl citrate 3.05

20 Polyethylene glycol -

21 Talc 9.299

22 Polysorbate 80 0.89

23 Purified water q.s

Total 331.37

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Chromatograms of optimized formulation

ASSAY CHROMOTOGRAMS:(Standard)

Figure 11: Assay chromatogram of standard.

PEAK RESULTS

LANSOPRAZOLE RETENTION TIME(MIN)

8.633 AREA 1580

Figure 12: Assay chromatogram of standard.

PEAK RESULTS:(Sample)

NAME RETENTION TIME(MIN) AREA LANSOPRAZOLE 8.631 1580

Table 13: Kinetic release studies for Innovator and Optimized formulation.

Optimized formulation Innovator

Release kinetics Correlation coefficient (r2) Correlation coefficient (r2) Zero order equation 0.993 0.583 First order equation 0.422 0.874 Higuchi (diffusion)co-efficient 0.998 0.852

Stability data of formulation

Stability studies were conducted at 40ºC / 75% RH for

about 3 months in stability chamber (Thermo lab).

Samples were collected at 1, 2 and 3 months.

Table 14: Stability data of optimized formulation.

Time

Period Test (%)

Temperature

40ºC / 75% RH

1 month Assay 99.1

Acid resistance 99.0

2 months Assay 99.1


3 months Assay 99.0


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Dissolution profile for stability samples at different storage conditions

Table 15: Dissolution profile for stability samples.

Time(min) 40ºC / 75% RH % drug release

1 month 2 months 3 months 10 51 51 50 20 75 73 72 30 85 84 84 45 98 98 97 60 96 95 95

Figure 13: In vitro dissolution profile of optimized formulation at 40ºC / 75% RH.

CONCLUSION

The present study was to formulate and evaluate delayed

release Capsules of Lansoprazole. The formulation

process was carried out in FBP by suspension layering

technique. Drug Loading was given to sugarsheres by

using different binders i.e., Klucel- LF and L- HPC with

different concentrations. The amount of drug bound to

sugarsheres increases with an increased concentration of

HPC(L-type) (17.5% and 22%). But at high

concentration of HPC (22%), lumps were observed.

Finally 17.5% w/w HPC was optimized as binder for

drug coating. Sub coating was given to drug loaded

pellets to avoid direct contact with enteric coating. Sub

coating was given with HPC and Corn starch

combination at an average weight build up of 6.1% w/w

of sub coated pellets. Enteric coating was given to

Lansoprazole pellets by Methacrylic acid copolymer type

C (30% aqueous dispersion). Enteric coating was

optimized at an average weight build up of 53% w/w of

enteric coated pellets and release profile was compared

with Innovator. In enteric coating, plasticizer plays major

role in film formation of pellets. Among TEC and PEG

6000, TEC was found to have good film forming

capacity. Plasticizer concentration was optimized at 20%

of dry polymer weight. Enteric coated pellets were

evaluated for assay, acid resistance and dissolution; E6

enteric coated pellets were found to be optimized and

were filled into capsules. These capsules were evaluated

and the results were found to be more similar with

innovator. Different kinetic models were applied to

optimized enteric coated formulation (E6) and observed

that it follows zero order kinetics with Higuchi diffusion

mechanism. Stability studies were conducted at 40ºC /

75% RH (accelerated stability testing) for 3 months.

Assay, acid resistance, dissolution release profile of

optimized enteric coated formulation (E6) complies with

Innovator and was found to be stable. Based on the

above data, it was concluded that Lansoprazole Capsules

30mg (E6) complies with the Innovator and may be

considered as an ideal formulation for developing

Lansoprazole delayed release capsules 30mg.

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http://www.sciencedirect.com/science/journal/03785173http://www.sciencedirect.com/science/journal/03785173http://www.sciencedirect.com/science?_ob=PublicationURL&_tockey=%23TOC%235069%231996%23998679998%2374002%23FLP%23&_cdi=5069&_pubType=J&view=c&_auth=y&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=fc167fb5c93927d74469f1bbe4865248http://www.mhra.gov.uk/home/groups/l-unit1/documents/websiteresources/con2032425.pdfhttp://www.mhra.gov.uk/home/groups/l-unit1/documents/websiteresources/con2032425.pdfhttp://www.mhra.gov.uk/home/groups/l-unit1/documents/websiteresources/con2032425.pdfhttp://www.mhra.gov.uk/home/groups/l-unit1/documents/websiteresources/con2032425.pdfhttp://www.mhra.gov.uk/home/groups/l-%20unit1/documents/websiteresources/con2032425.pdfhttp://www.mhra.gov.uk/home/groups/l-%20unit1/documents/websiteresources/con2032425.pdfhttp://www.mhra.gov.uk/home/groups/l-%20%20%20unit1/documents/websiteresources/con2032425.pdfhttp://www.mhra.gov.uk/home/groups/l-%20%20%20unit1/documents/websiteresources/con2032425.pdf

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