DESIGN AND IN VITRO EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF LORNOXICAM

DESIGN AND

IN-VITRO

EVALUATION OF SUSTAINED RELEASE

MATRIX TABLETS OF LORNOXICAM

Senthil Kumar K*, Ameer Basha Pothuganti, Mohammed Gulzar Ahmed

Department of Pharmaceutics, Sri Adichunchanagiri college of Pharmacy, B.G. Nagara,

Karnataka-571448.

ABSTRACT

The aim of the present work was to develop sustained release matrix

tablets of Lornoxicam using polymers such as carbopol, Eudragit

RS100, polyvinylpyrrolidone, ethyl cellulose, pectin as carriers in

various concentrations. Matrix tablets were prepared by direct

compression method. Prepared formulations were subjected to various

evaluation parameters like hardness, friability, thickness, % drug

content, weight variation etc. In-vitro dissolution studies were carried

out for 12 hrs. The tablets were subjected to in-vitro drug release in 1.2

pH for first 2 hrs then followed by 6.8 pH phosphate buffer for next 10

hrs and the results showed that among the ten formulations F2 and F4

showed good dissolution profile to control the drug release

respectively. Combination of polymers shows greater retarding of drug

release. The compatibility of the drug and polymer were determined by FT-IR spectroscopy.

Results showed that the drug was compatible with all polymers. The release data was fitted to

various mathematical models such as Higuchi, Korsmeyer-peppas, Hixson crowell, Zero

order and first order to evaluate the kinetics of drug release. The drug release follows mixed

order kinetics and mechanism was found to be non-fickian diffusion. The stability studies

were carried out according to the ICH guideline which indicates the selected formulation (F2

& F4) was stable. In conclusion, the results suggest that the developed matrix tablets of

Lornoxicam shows to improved efficacy and better patient compliance.

KEYWORDS: Sustained release, Matrix tablets, Lornoxicam, carbopol, Eudragit RS100, Polyvinylpyrrolidone, Ethylcellulose, pectin.

Volume 4, Issue 9, 1063-1074. Research Article ISSN 2277– 7105

Article Received on 05 July 2015,

Revised on 26 July 2015, Accepted on 17 Aug 2015

*Correspondence for

Author

Senthil Kumar K

Department of

Pharmaceutics, Sri

Adichunchanagiri college

of Pharmacy, B.G.

Nagara,

INTRODUCTION

Oral drug delivery continues to rise in popularity as formulation scientists look for ways to

control drug release and improve patient convenience. However, developing oral controlled

release tablets for water soluble drugs with constant release rate has always been a challenge

to the pharmaceuticals technologist. Most of these water-soluble drugs, if not formulated

properly may readily release the drug at a faster rate and produce a toxic concentration of the

drug on oral administration.[1]

The basic goal of therapy is to achieve a steady state drug in blood level for an extended

period of time. The design of proper dosage regimens is an important element in

accomplishing this goal. Sustained release, Sustained action, Prolonged action controlled

release. Extended action, time release depot and repository dosage forms are terms used to

identify drug delivery system than are designed to achieve a prolonged therapeutic effect by

continuously releasing medication over an extended period of time after administration of

single dose. In the case of injectable dosage form, this period may vary from day to months.

In the case of orally administrated dosage forms, this period measures in hours and critically

depends on the residence time of the dosage form in the gastrointestinal tract. The term

controlled release has been associated with those systems from which therapeutic agents may

be automatically delivery at predetermined rates over a long period of time. Products of this

type have been formulated for oral injectable and topical use and inserts for placement in the

body cavities.[2] Lornoxicam (Chlortenoxicam), is a non-steroidal Anti-inflammatory drug

(NSAID) of the oxicam class. It has analgesic, anti-inflammatory and anti-pyretic properties.

Lornoxicam is also as a NSAID in relieving symptoms of osteoarthritis, rheumatoid arthritis,

ankylosing spondylitis, acute sciatica and low back pain.Lornoxicam has half-life of 3 to 5

hrs. So, patients are routinely asked to take Lornoxicam for several times in a day. Such

frequent drug administration may reduce patient’s compliance and therapeutic efficacy.[3]

MATERIALS AND METHODS Standard Curve for Lornoxicam

100 mg of Lornoxicam was accurately weighed and dissolved in 100 ml of pH 1.2 to prepare

first stock solution. 5ml of above solution was taken and diluted to 100 ml with the same

solvent to prepare II stock solution. The aliquot amount of stock solution II was further

final solution. Then the absorbance was measured in a UV spectrophotometer at 376 nm

against pH 1.2 as blank. The same procedure was repeated by using phosphate buffer pH 6.8.

Compatibility study using FT-IR: The IR spectrum of drug was recorded using Tensor 27,

Bruker. The observations are shown in figure.

Formulation development of sustained release matrix tablets of Lornoxicam

Table 1.Formulations containing various concentrations of excipients

Preparation of Lornoxicam matrix tablets: 6mgof Lornoxicam along with various polymers

such as carbopol, eudragit RS100, ethyl cellulose, polyvinylpyrrolidone, pectin other

excipients (talc, magnesium stearate and MCC) were mixed and tablets were prepared by

direct compression technique. Desired amount of blend was directly compressed into tablets

using rotary tablet compression machine (Multi punch machine). Before compression, the

surface of the die and punch were lubricated with magnesium stearate. All the preparations

were stored in airtight container at room temperature for further studies.

EVALUATION OF LORNOXICAM MATRIX TABLETS

The matrix tablets prepared were evaluated for the following parameters:

Weight variation

Hardness

Friability

Drug content

In-vitro Dissolution Studies

Stability Studies Ingredients F1 mg/ta b F2 mg/ta b F3 mg/ta b F4 mg/ta b F5 mg/t ab F6 mg/tab F7 mg/t ab F8 mg/ta b F9 mg/ta b F10 mg/ta b

Lornoxicam 6 6 6 6 6 6 6 6 6 6

Carbopol 6 12 - - - -

Eudragit RS100 - - 6 12 - - - -

Ethyl cellulose - - - - 6 12 - - - -

Polyvinylpyrrolidone - - - 6 12 - -

Pectin - - - 6 12

Magnesium stearate 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4 2.4

Talc 4 4 4 4 4 4 4 4 4 4

Micro Crystalline

Cellulose q.s q.s q.s q.s q.s q.s q.s q.s q.s q.s

Weight Variation Test

To study weight variation, 20 tablets of each formulation were weighed using an electronic

balance and the test was performed according to the official method.

Table 2.IP standards of Uniformity of weight

Sl.No AvgWt of Tablet % of Deviation

1 ≤ 80mg 10

2 >80 mg – 250 mg 7.5

3 ≥ 250 mg 5

Hardness and Friability

For each formulation, the hardness and friability of 6 tablets were determined using the

Monsanto hardness tester (Cadmach, Ahmedabad, India) and the Roche friabilator (Campbell

Electronics, Mumbai, India) respectively.

Drug Content: Ten tablets were weighed and average weight is calculated. All tablets were

crushed and powder equivalent to 6 mg drug was dissolved in 6 ml of 0.1N NaOH and the

volume was made up to 100 ml with pH 6.8 phosphate buffer. The solution was shaken for 1

h and kept for 24 h. From the stock solution, 1ml solution was taken in 10 ml volumetric

flask and the volume was made with pH 6.8 phosphate buffer. Solution was filtered and

absorbance was measured spectrophotometrically at 376 nm against pH 6.8 phosphate buffer

as a blank. Amount of drug present in one tablet was calculated.

In-vitro dissolution studies

The in-vitro dissolution studies were performed using the USP-II (Paddle) dissolution

apparatus at 50 rpm.Two dissolution medias-acidic buffer pH 1.2 for 2hrsand phosphate

buffer pH 6.8 for 10hrs.Medium is maintained at 37±0.50C. A 5ml was withdrawn at specific

time intervals of 1 hrupto12 hr and same volume of fresh medium was replaced. The

withdrawn samples were diluted to 5ml with pH 6.8, filtered and analyzed on UV

spectrophotometer at 376 nm using pH 6.8 as a blank. Percentage cumulative drug release was

calculated.

STABILITY STUDIES

The optimized formulation was subjected for two month stability study according to ICH

mouth bottles closed tightly. They were then stored at 25ºC/ 60% RH, 40ºC / 75% RH for 3

months and evaluated for their permeation study.

RESULTS AND DISCUSSION

Calibration Curve of Lornoxicam in 1.2 pH buffer.

The absorbance was measured in a UV spectrophotometer at 376 nm against 1.2pH buffer.

Figure 1Calibration Curve of Lornoxicam in 1.2 pH buffer.

Calibration Curve of Lornoxicam in 6.8 pH buffer

The absorbance was measured in a UV spectrophotometer at 376 nm against 6.8pH buffer.

Figure 2 Calibration Curve of Lornoxicam in 6.8 pH buffer. FT-IR spectrum

Infra red spectrum of drug and polymers were recorded over KBr disc method.

Drug-Lornoxicam

Figure 3FT-IR Spectrum of Lornoxicam

Table 3.Compatibility of Lornoxicam

FT-IR spectrum Functional group Wave number(cm-1)

Lornoxicam

S=O 1124

C=O 1646

N-H 2923

Figure 4.IR Spectrum of Lor+Carbopol

Table 4.Compatibility of Lor+Carbopol

FT-IR spectrum Functional group Wave number(cm-1)

Lor + Carbopol

S=O 1124

N-H 2928

Figure 5.FT-IR Spectrum of Lor+Eudragit

Table 5.Compatibility of Lor+Eudragit

IR spectrum Functional group Wave number(cm-1)

Lor+Eudragit

S=O 1123

N-H 2920

C-N 1262

Figure 6.FT-IR Spectrum of Lor+Pvp

Table 6.Compatibility of Lor+Pvp

FT-IR spectrum Functional group Wave number(cm-1)

Lor+Pvp

S=O 1123

C-N 1158

Figure 7.FT-IR Spectrum of Lor+EC

Table 7.Compatibility of Lor+Ethyl cellulose

FT-IR spectrum Functional group Wave number(cm-1) Lor+EC

N-H 2977

S=O 1120

C-O-H 1383

Figure 8. FT-IR Spectrum of Lor+Pectin

Table 8.Compatibility of Lor+Pectin

FT-IR spectrum Functional group Wave number(cm-1)

Lor+Pectin

S=O 1145

C-N 1239

C=O 1646

Table 9.Compatibility of F2 formulation

FT-IR spectrum Functional group Wave number(cm-1) F2 formulation

S=O 1026

C-N 1162

Figure 9.FT-IR Spectrum of F2 formulation

Table 10.Post Compression Evaluation Parameters Formulation Weight Variation

(mg)

Hardness (Kg/cm2)

Friability (%)

Thickness (mm)

Drug content (%)

F1 99.54±0.46 3.4±0.25 0.14±0.01 2.22±0.05 97.21±0.29

F2 99.44±0.56 3.2±0.29 0.18±0.076 2.27±0.04 97.51±0.49

F3 99.33±0.67 3.5±0.26 0.25±0.013 2.21±0.05 98.34±0.21

F4 98.55±0.23 3.3±0.24 0.55±0.30 2.16±0.02 98.11±0.82

F5 100.5±0.40 3.6±0.27 0.13±0.06 2.25±0.17 99.57±0.33

F6 99.14±0.86 3.1±0.22 0.17±0.04 2.10±0.01 99.56±0.83

F7 99.24±0.76 3.5±0.26 0.58±0.66 2.24±0.17 98.34±0.21

F8 99.76±0.24 3.8±0.28 0.69±0.46 2.22±0.01 97.51±0.49

F9 99.88±0.12 3.9±0.29 0.59±0.66 2.19±0.02 99±0.81

F10 99.57±0.43 3.2±0.23 0.25±0.103 2.10±0.01 98.37±0.67

Table 11.In-vitro drug release profiles of Formulation F1 to F10. Time

(min) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10

0 0 0 0 0 0 0 0 0 0 0

60 8.1 10.8 7.2 9.99 6.21 6.3 5.4 6.3 4.77 5.22

Figure 10.Cumulative percentage release Vs Time profile of formulations F1,F2,F3,F4

Figure 11.Cumulative percentage release Vs Time profile of formulations F5, F6, F7, F8, F9, F10

STABILITY STUDIES

The best formulations F2 and F4 subjected to stability studies at 40 /75% RH and room

temperature for 2 months. Then the tablets were analysed for physical change, drug content

estimation and in-vitro dissolution studies at an interval of 15 days. Results show that after

analyzing there was no change in case of physical appearance, no significant differences in

the drug content and dissolution study.

CONCLUSION

The present study was carried out to develop sustained release matrix tablets of Lornoxicam

using polymers such as carbopol, EudragitRS100, polyvinylpyrrolidone, ethyl cellulose,

pectin alone and in combinations by direct compression method.Based on the IR studies there

is no possibility of interaction between Lornoxicam and carbopol, Eudragit RS100,

polyvinylpyrrolidone, ethyl cellulose and pectin.

All the prepared formulations were evaluated for both pre-compressive and post-compressive

parameters such as melting point, solubility studies, compatibility studies, angle of repose,

bulk density, tapped density, carr’s index, hausner’s ratio, tablet thickness, hardness,

friability, weight variation and drug content uniformity, the values obtained were found to be

satisfactory and they complies with pharmacopoeial standards.The tablets were subjected to

in-vitro drug release in 1.2 pH for first 2 hrs then followed by 6.8pH phosphate buffer for 10

hrs. Combination of polymers shows greater retarding of drug release. From the above

experimental data it can be concluded that the sustained release matrix tablets of Lornoxicam

have been developed for improved therapeutic efficacy and better patient compliance. The

formulations F2 and F4 produced better controlled with 92.0%and 87.85% of drug release

over a period of 12hrs in comparison to other formulations.

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