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INTERNATIONAL JOURNAL OF<br />
RESEARCH ARTICLE<br />
PHARMACEUTICAL INNOVATIONS ISSN 2249-1031<br />
FORMULATION AND EVALUATION OF LORNOXICAM MICROSPONGE<br />
TABLETS FOR THE TREATMENT OF ARTHRITIS<br />
*Karthika.R , Elango.K , Ramesh Kumar.K , Rahul.K<br />
Department <strong>of</strong> Pharmaceutics, College <strong>of</strong> Pharmacy, Madras Medical College, Chennai, India<br />
Abstract<br />
The purpose <strong>of</strong> this study was to design novel drug delivery system containing Lornoxicam<br />
<strong>microsponge</strong>s. Lornoxicam is a Non-steroidal anti-inflammatory drug used for the treatment<br />
<strong>of</strong> various inflammatory diseases. Microsponges containing Lornoxicam <strong>and</strong> Eudragit RS<br />
100 were prepared by quasi emulsion solvent diffusion method. The effects <strong>of</strong> drug to<br />
polymer ratios on physical characteristics <strong>of</strong> the <strong>microsponge</strong>s were investigated.<br />
Compatibility <strong>of</strong> drug with adjuncts was studied by FT-IR. Production yield, loading<br />
efficiency, particle size analysis, surface morphology <strong>and</strong> in-vitro release studies were carried<br />
out. The <strong>microsponge</strong>s were compressed into <strong>tablets</strong>. Mechanically strong <strong>tablets</strong> were<br />
obtained owing to the plastic deformation <strong>of</strong> sponge-like structure <strong>of</strong> <strong>microsponge</strong>s. The<br />
effects <strong>of</strong> different stirring rates, amount <strong>of</strong> solvent, amount <strong>of</strong> emulsifier used on the<br />
physical characteristics <strong>of</strong> the <strong>microsponge</strong>s were investigated. All the factors studied had an<br />
influence on the physical characteristics <strong>of</strong> the <strong>microsponge</strong>s. In-vitro dissolution studies<br />
were done on all <strong>formulation</strong>s <strong>and</strong> the results were kinetically evaluated <strong>and</strong> the release rate<br />
<strong>of</strong> Lornoxicam was found to be modified. This study presents a new approach based on<br />
<strong>microsponge</strong> drug delivery system.<br />
Keywords: Microsponges, Lornoxicam, Quasi-emulsion solvent diffusion method,<br />
Morphology, Release kinetics<br />
INTRODUCTION<br />
Many <strong>of</strong> conventional delivery systems<br />
require high concentrations <strong>of</strong> active<br />
agents to be incorporated for effective<br />
therapy because <strong>of</strong> their low efficiency as<br />
delivery systems. Thus novel drug delivery<br />
systems have been increasingly<br />
investigated to achieve targeted <strong>and</strong><br />
controlled release <strong>of</strong> drugs. Microsponges<br />
are highly crosslinked, patented, porous,<br />
polymeric microspheres that acquire the<br />
flexibility to entrap a wide variety <strong>of</strong><br />
active ingredients that are mostly used for<br />
Volume 3, Issue 2, March − April 2013<br />
prolonged topical administration <strong>and</strong><br />
recently for oral administration.<br />
Microsponges are designed to deliver a<br />
pharmaceutically active ingredient<br />
efficiently at minimum dose <strong>and</strong> also to<br />
enhance stability, elegance, flexibility in<br />
<strong>formulation</strong>, reduce side effects <strong>and</strong><br />
[1, 2]<br />
modify drug release pr<strong>of</strong>iles.<br />
Microsponges are prepared by several<br />
*Corresponding author<br />
Karthika.R<br />
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PHARMACEUTICAL INNOVATIONS ISSN 2249-1031<br />
methods utilizing emulsion systems as<br />
well as by suspension polymerization in a<br />
liquid-liquid system. The most common<br />
emulsion system used is Quasi-emulsion<br />
solvent diffusion method. [2]<br />
Lornoxicam, a congener <strong>of</strong> tenoxicam, is<br />
a new NSAID belonging to the oxicam<br />
class. It is a strong analgesic <strong>and</strong> antiinflammatory<br />
NSAID as compared to<br />
other NSAIDs. Chemically its 6-chloro-<br />
4-hydroxy-2-methyl-N-2-pyridyl-2Hthieno-[2,<br />
3-e]-1, 2-Thiazine-3-<br />
carboxamide-1,1-dioxide. Like all<br />
NSAIDs, it acts by inhibiting the<br />
metabolites <strong>of</strong> COX branch <strong>of</strong><br />
arachidonic acid pathway. Half-life <strong>of</strong><br />
Lornoxicam is 3-5 hours, which increases<br />
the dosing frequency <strong>of</strong> the drug. The<br />
increased dosing frequency leads to side<br />
effects. Thus the present study is aimed at<br />
developing <strong>microsponge</strong> based novel<br />
drug delivery system containing<br />
Lornoxicam. The <strong>microsponge</strong>s <strong>of</strong><br />
Lornoxicam were prepared <strong>and</strong><br />
characterized. They were formulated as<br />
<strong>tablets</strong> <strong>and</strong> subjected to in-vitro<br />
characterization for various attributes. [3]<br />
MATERIAL AND METHODS<br />
Lornoxicam was obtained as a gift<br />
sample from Glenmark Pharmaceuticals<br />
Ltd., Eudragit RS 100 was obtained from<br />
MMC Healthcare, Chennai, Polyvinyl<br />
alcohol was procured from S.D Fine-<br />
Chem Limited, Mumbai, Triethyl citrate<br />
was purchased from Himedia laboratories<br />
Pvt.Ltd, Ethanol was from<br />
ChangshuYangyuan Chemical, China,<br />
Magnesium stearate from Indian<br />
Research Products, Chennai, Micro<br />
crystalline cellulose from Kniss<br />
Volume 3, Issue 2, March − April 2013<br />
Laboratories, Chennai, Talc from S.S<br />
Chemicals, Chennai, Lactose from<br />
Micr<strong>of</strong>ine Chemicals, India. All other<br />
chemicals <strong>and</strong> solvents were <strong>of</strong> analytical<br />
reagent grade.<br />
Preparation <strong>of</strong> Lornoxicam<br />
<strong>microsponge</strong>s<br />
Lornoxicam <strong>microsponge</strong>s were prepared<br />
by quasi emulsion solvent diffusion<br />
method. The internal phase consisted <strong>of</strong><br />
Eudragit RS 100 (100mg) <strong>and</strong> triethyl<br />
citrate dissolved in 5ml ethanol. Triethyl<br />
citrate was used as plasticizer. This was,<br />
followed by addition <strong>of</strong> drug with gradual<br />
stirring. The internal phase was then<br />
poured into polyvinyl alcohol (0.5%w/v)<br />
solution in water, the external phase.<br />
After 2 hours <strong>of</strong> stirring the <strong>microsponge</strong>s<br />
were formed due to the removal <strong>of</strong><br />
ethanol from the system. The<br />
<strong>microsponge</strong>s were filtered <strong>and</strong> dried at<br />
40˚C for 24 hours. The composition <strong>of</strong><br />
<strong>microsponge</strong> <strong>formulation</strong>s are given in<br />
table1.<br />
Fourier transform infrared analysis<br />
Infrared spectroscopy was conducted<br />
using FT-IR spectrophotometer <strong>and</strong> the<br />
spectrum was recorded in the wavelength<br />
region <strong>of</strong> 4000 to 400 cm -1 . The<br />
procedure consisted <strong>of</strong> dispersing the<br />
sample (drug alone, mixture <strong>of</strong> drug <strong>and</strong><br />
excipients <strong>and</strong> the optimized <strong>formulation</strong>)<br />
in KBr <strong>and</strong> compressed into discs by<br />
applying a pressure <strong>of</strong> 5 tons for 5<br />
minutes in a hydraulic press. The pellet<br />
was placed in the light path <strong>and</strong> the<br />
spectrum was recorded. [4]<br />
Surface morphology <strong>of</strong> <strong>microsponge</strong>s<br />
The surface morphology <strong>of</strong> the prepared<br />
<strong>microsponge</strong>s was examined using a<br />
scanning electron microscope, operating at<br />
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PHARMACEUTICAL INNOVATIONS ISSN 2249-1031<br />
20 kV. Dried <strong>microsponge</strong>s were coated<br />
with gold–palladium alloy for 45sec under<br />
an argon atmosphere before observation.<br />
SEM photograph was recorded at different<br />
magnifications using Tescan VEGA3SBU<br />
SEM analyzer. [5]<br />
Determination <strong>of</strong> percentage yield [5]<br />
The production yield <strong>of</strong> the <strong>microsponge</strong>s<br />
was determined by calculating accurately<br />
the initial weight <strong>of</strong> the raw materials <strong>and</strong><br />
the weight <strong>of</strong> the <strong>microsponge</strong> obtained,<br />
W Pr<br />
Production yield = × 100<br />
W Th<br />
Where-<br />
W Pr = Practical mass <strong>of</strong> <strong>microsponge</strong>s<br />
W Th = Theoretical mass (polymer + drug)<br />
Determination <strong>of</strong> loading efficiency [5]<br />
Lornoxicam <strong>microsponge</strong>s equivalent to<br />
50 mg <strong>of</strong> the drug was taken in a 100 ml<br />
st<strong>and</strong>ard flask. 25 ml ethanol <strong>and</strong> 25ml <strong>of</strong><br />
6.8 pH phosphate buffer were added <strong>and</strong><br />
shaken for about half an hour <strong>and</strong> the<br />
volume was made upto 100 ml with 6.8 pH<br />
phosphate buffer. 2 ml <strong>of</strong> the solution was<br />
taken <strong>and</strong> diluted to 100 ml with 6.8 pH<br />
phosphate buffer. The absorbance <strong>of</strong> the<br />
resulting solution was measured at 376 nm<br />
<strong>and</strong> the content <strong>of</strong> LOX was calculated.<br />
The loading efficiency (%) <strong>of</strong> the<br />
<strong>microsponge</strong>s was calculated.<br />
DC act<br />
Loading efficiency = × 100<br />
DC Theo.<br />
DC act. = Actual drug content in<br />
<strong>microsponge</strong>s<br />
DC Theo. = Theoretical drug content<br />
Volume 3, Issue 2, March − April 2013<br />
Particle size analysis<br />
Particle size <strong>and</strong> size distribution <strong>of</strong><br />
<strong>microsponge</strong> particles was determined<br />
using optical microscope. The values are<br />
given for the <strong>formulation</strong>s in the form <strong>of</strong><br />
mean particle size.<br />
Micromeritic properties<br />
The drug <strong>and</strong> blend <strong>of</strong> drug with excipients<br />
were evaluated for bulk density, tapped<br />
density, compressibility index, Hausner’s<br />
[6, 7]<br />
ratio <strong>and</strong> angle <strong>of</strong> repose.<br />
Preparation <strong>of</strong> tablet <strong>formulation</strong>s<br />
After the preparation <strong>of</strong> <strong>lornoxicam</strong><br />
<strong>microsponge</strong>s, they were formulated as<br />
<strong>tablets</strong> by “Direct compression method”.<br />
All the ingredients were weighed<br />
accurately <strong>and</strong> mixed thoroughly. The<br />
lubricated blend was then compressed<br />
using 8 mm flat face punch. The<br />
composition <strong>of</strong> different <strong>formulation</strong>s used<br />
in the study is shown in Table 2.<br />
Evaluation <strong>of</strong> Lornoxicam <strong>microsponge</strong><br />
<strong>tablets</strong><br />
The <strong>tablets</strong> <strong>of</strong> <strong>lornoxicam</strong> were evaluated<br />
for uniformity <strong>of</strong> weight. Thickness <strong>and</strong><br />
diameter were measured by vernier<br />
calipers. Hardness was determined using<br />
Monsanto hardness tester <strong>and</strong> friability <strong>of</strong><br />
<strong>tablets</strong> was determined by Roche<br />
friabilator. [7]<br />
Disintegration test<br />
One tablet was placed in each <strong>of</strong> the six<br />
tubes <strong>of</strong> basket, the assembly was<br />
suspended in water, maintained at<br />
temperature 37˚C±2˚C <strong>and</strong> the apparatus<br />
was operated. The time taken to<br />
disintegrate the tablet completely was<br />
noted. [7]<br />
Drug content<br />
Ten <strong>tablets</strong> were weighed <strong>and</strong> ground. The<br />
weight equivalent to 8 mg <strong>of</strong> drug was<br />
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taken <strong>and</strong> transferred to a 100 ml st<strong>and</strong>ard<br />
flask. 25 ml <strong>of</strong> ethanol <strong>and</strong> 25 ml <strong>of</strong> 6.8<br />
pH phosphate buffer were added <strong>and</strong><br />
shaken for about half an hour <strong>and</strong> the<br />
volume was made up to 100 ml with 6.8<br />
pH phosphate buffer. The above solution<br />
was filtered <strong>and</strong> 5 ml <strong>of</strong> filtrate was taken<br />
<strong>and</strong> diluted to 100 ml with 6.8 pH<br />
phosphate buffer. The absorbance <strong>of</strong> the<br />
resulting solution was measured at 376 nm<br />
<strong>and</strong> the content <strong>of</strong> Lornoxicam was<br />
[7, 8]<br />
calculated.<br />
Uniformity <strong>of</strong> content<br />
Six <strong>tablets</strong> were r<strong>and</strong>omly selected <strong>and</strong><br />
tested for their drug content. The content<br />
<strong>of</strong> active ingredients <strong>of</strong> various<br />
<strong>formulation</strong>s was calculated by measuring<br />
the absorbance <strong>of</strong> diluted solutions using<br />
UV-Visible Spectrophotometer at 376 nm.<br />
[7]<br />
In-vitro drug release studies<br />
Two step dissolution conditions was used<br />
in USP Type II (paddle) dissolution<br />
apparatus to simulate the physiological<br />
conditions <strong>of</strong> GIT – 2 hours in 900 ml <strong>of</strong><br />
simulated gastric fluid (SGF, pH 1.2) <strong>and</strong><br />
10 hours in 900 ml <strong>of</strong> simulated intestinal<br />
fluid (SIF, pH 6.8). The stirring rate was<br />
100 rpm <strong>and</strong> the temperature was<br />
maintained at 37 ± 0.5˚C. Aliquots <strong>of</strong><br />
dissolution medium were withdrawn at<br />
predetermined time intervals <strong>and</strong> the same<br />
volume <strong>of</strong> medium was replenished to<br />
maintain the constant volume. The<br />
absorbance <strong>of</strong> the solutions was measured<br />
at 376 nm <strong>and</strong> the release was calculated.<br />
[8]<br />
Drug release kinetics<br />
The dissolution pr<strong>of</strong>ile <strong>of</strong> optimized<br />
<strong>formulation</strong> was subjected to various<br />
models such as Zero order kinetics<br />
Volume 3, Issue 2, March − April 2013<br />
(percentage drug release against time),<br />
First order kinetics (log percentage drug<br />
unreleased against time), Higuchi<br />
(percentage drug released against square<br />
root <strong>of</strong> time), Korsemeyer-Peppas (log<br />
percent drug released against log <strong>of</strong> time)<br />
<strong>and</strong> Hixson-Crowell (cube root <strong>of</strong><br />
cumulative percentage <strong>of</strong> drug remaining<br />
against time) to assess the kinetics <strong>of</strong> drug<br />
release from prepared Lornoxicam<br />
<strong>microsponge</strong>s.<br />
RESULTS AND DISCUSSION<br />
Compatibility studies<br />
FT-IR spectra were recorded to assess the<br />
compatibility <strong>of</strong> the drug <strong>and</strong> excipients.<br />
FT-IR spectra <strong>of</strong> drug, physical mixture <strong>of</strong><br />
drug <strong>and</strong> excipients were examined. In FT-<br />
IR spectra <strong>of</strong> Lornoxicam powder,<br />
characteristic O-H stretching b<strong>and</strong> at<br />
3448.47 cm -1 , C-Cl stretching b<strong>and</strong> at<br />
794.61 cm -1 , SO 2 streching b<strong>and</strong> at<br />
1427.22 cm -1 <strong>and</strong> aromatic C=S stretching<br />
b<strong>and</strong> at 1188.06 cm -1 were seen. These are<br />
the major peaks <strong>of</strong> the spectra <strong>of</strong> the drug.<br />
All these peaks were present in the spectra<br />
<strong>of</strong> <strong>formulation</strong> <strong>and</strong> thus confirm that the<br />
drug did not interact with the excipients.<br />
Evaluation <strong>of</strong> <strong>microsponge</strong><br />
Particle size <strong>and</strong> shape<br />
The SEM photographs <strong>of</strong> the<br />
<strong>microsponge</strong>s are shown in figure 4.<br />
Particle size analysis showed the particle<br />
size ranging from 75.6 to 45.5 µm <strong>and</strong><br />
spherical in shape. Mean particle size <strong>of</strong><br />
<strong>formulation</strong>s M1 to M5 is given in table 4.<br />
Production yield <strong>and</strong> loading efficiency<br />
Production yield <strong>and</strong> loading efficiency <strong>of</strong><br />
Lornoxicam <strong>microsponge</strong> <strong>formulation</strong> are<br />
given in table 4. Batch M1 to M5 shows<br />
production yield in the range <strong>of</strong> 69.35 to<br />
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89.65 % <strong>and</strong> loading efficiency in the<br />
range <strong>of</strong> 89.25 to 96.39 % as shown in<br />
table 4.<br />
Evaluation <strong>of</strong> <strong>tablets</strong><br />
Micromeritic properties<br />
The Lornoxicam <strong>microsponge</strong> blends were<br />
free flowing as indicated by the values <strong>of</strong><br />
bulk density (0.479 to 0.510 g/ml), tapped<br />
density (0.534 to 0.585 g/ml),<br />
compressibility index (10.29 to 12.82%)<br />
<strong>and</strong> Hausner’s ratio (1.11 to 1.14). Angle<br />
<strong>of</strong> repose ranged from 29.11 to 31.16. The<br />
values are given in Table 3.<br />
Physical <strong>evaluation</strong> <strong>and</strong> Drug content<br />
The Lornoxicam <strong>microsponge</strong> <strong>tablets</strong> were<br />
uniform in weight (0.178 to 0.181g). The<br />
thickness (2.5 mm) <strong>and</strong> diameter (8.00<br />
mm) <strong>of</strong> the <strong>tablets</strong> were uniform. The<br />
hardness <strong>of</strong> <strong>tablets</strong> was found to be<br />
between 4.25 <strong>and</strong> 4.75 kg/cm2, while the<br />
friability <strong>of</strong> the <strong>tablets</strong> ranged between<br />
0.44 <strong>and</strong> 0.6 %. The <strong>tablets</strong> have enough<br />
hardness to withst<strong>and</strong> stress during<br />
transport <strong>and</strong> h<strong>and</strong>ling. The disintegrating<br />
time <strong>of</strong> the various <strong>formulation</strong>s were<br />
found to be between 2.12 <strong>and</strong> 3.0 min.<br />
Disintegrating time was found to be within<br />
the limits as the maximum time for<br />
uncoated <strong>tablets</strong> is 30 min. The drug<br />
content in various <strong>formulation</strong>s varied<br />
between 91.22 <strong>and</strong> 100.6% w/w. (Table 5)<br />
[8]<br />
Uniformity <strong>of</strong> Drug content<br />
The percentage <strong>of</strong> drug content <strong>of</strong> all the<br />
<strong>formulation</strong>s ranged from 96.85 <strong>and</strong> 100.7<br />
% w/w. All the <strong>formulation</strong>s comply with<br />
the test for uniformity <strong>of</strong> content.<br />
In-vitro drug release<br />
The release pr<strong>of</strong>iles obtained for the<br />
<strong>microsponge</strong> <strong>tablets</strong> are presented in figure<br />
Volume 3, Issue 2, March − April 2013<br />
1. The pr<strong>of</strong>iles showed a bi-phasic release<br />
with an initial burst effect. In the first 2<br />
hrs, about 13 to 27% <strong>of</strong> the drug was<br />
released. Cumulative release for the<br />
<strong>microsponge</strong>s after 12 hrs ranged from 86-<br />
96%. Drug release from the <strong>formulation</strong>s<br />
decreased with increase in the amount <strong>of</strong><br />
polymer in the <strong>microsponge</strong>s. [9]<br />
Release Kinetics <strong>of</strong> the Optimized<br />
<strong>formulation</strong><br />
The R 2 values for various release models<br />
are 0.919 for Zero order, 0.994 for First<br />
order, 0.966 for Higuchi, 0.948 for<br />
Korsemeyer-Peppas <strong>and</strong> 0.991 for Hixson-<br />
Crowell kinetics. The drug release follows<br />
first order kinetics <strong>and</strong> the mechanism<br />
followed is Hixson-Crowell.<br />
Effect <strong>of</strong> stirring rate on <strong>microsponge</strong>s<br />
The effect <strong>of</strong> stirring rate on the size <strong>of</strong><br />
<strong>microsponge</strong>s was studied. As the stirring<br />
speed was increased, <strong>microsponge</strong>s <strong>of</strong><br />
smaller size were obtained. When the rate<br />
<strong>of</strong> stirring was increased from 200 to 400<br />
rpm, the mean particle size decreased from<br />
59.67 µm to 35.81µm. It was also<br />
observed that at higher stirring rates<br />
employed, turbulence was created within<br />
the external phase, polymer then adhered<br />
to the stirrer <strong>and</strong> the production yield<br />
decreased, but the drug content increased,<br />
as shown in table 6. [9]<br />
Effect <strong>of</strong> volume <strong>of</strong> internal phase on<br />
<strong>microsponge</strong>s<br />
It was observed that on increasing the<br />
volume <strong>of</strong> internal phase from 5 to 15 ml<br />
<strong>microsponge</strong>s were not formed. This may<br />
be due to the decrease in viscosity <strong>of</strong><br />
internal phase. It was observed that the<br />
particle size, production yield <strong>and</strong> drug<br />
content decreased on increasing internal<br />
phase volume. The result suggests that the<br />
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amount <strong>of</strong> ethanol need to be controlled<br />
within an appropriate range to affect not<br />
only the formation <strong>of</strong> quasi-emulsion<br />
droplets at the initial stage but also the<br />
solidification <strong>of</strong> drug <strong>and</strong> polymer in the<br />
droplets. The good <strong>microsponge</strong>s were<br />
produced only when 5 ml <strong>of</strong> internal phase<br />
was used, as shown in table 7. [10]<br />
Effect <strong>of</strong> amount <strong>of</strong> emulsifying agent<br />
on <strong>microsponge</strong>s<br />
The production yield <strong>and</strong> mean particle<br />
size were greatly affected by the amount <strong>of</strong><br />
emulsifying agent. The increase in the<br />
amount <strong>of</strong> emulsifying agent resulted in<br />
larger <strong>microsponge</strong>s. This could be due to<br />
the increased viscosity. The increased<br />
amount <strong>of</strong> emulsifying agent decreased the<br />
production yield <strong>and</strong> drug content but<br />
increased the mean particle size as shown<br />
in the table 8. [10]<br />
Conclusion<br />
This study presents a new approach for the<br />
preparation <strong>of</strong> modified <strong>microsponge</strong>s with<br />
prolonged release characteristics. The<br />
prepared <strong>microsponge</strong>s exhibited<br />
characteristics <strong>of</strong> an ideal delivery system.<br />
The unique compressibility <strong>of</strong><br />
<strong>microsponge</strong>s <strong>of</strong>fers a new alternative for<br />
producing mechanically strong <strong>tablets</strong>.<br />
References<br />
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<strong>evaluation</strong> <strong>of</strong> Etodolac entrapped in<br />
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Pharmacy 2011; 1(2): 73-80.<br />
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Viral H Shah, Umesh Upadhyay.<br />
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Lornoxicam : A Newer NSAID.<br />
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Shaikh Siraj, Tarique Khar, Siddik<br />
Patel M, Mohammad Zameeruddin,<br />
Arshad Shaikh. Formulation <strong>and</strong><br />
<strong>evaluation</strong> <strong>of</strong> sustained release<br />
<strong>tablets</strong> <strong>of</strong> Acecl<strong>of</strong>enac using<br />
hydrophilic matrix system. IJPPS<br />
2011; 3(2): 145-148.<br />
5. Sarat Ch<strong>and</strong>ra Prasad M, Ajay M<br />
B, Nagendra Babu, Prathyusha P,<br />
Audinarayana N, Bhaskar Reddy<br />
K. Microsponge Drug Delivery<br />
System : A Review. Journal <strong>of</strong><br />
Pharmacy Research 2011; 4(5):<br />
1381-1384.<br />
6. Debajyoti Ray, Amresh K Prusty.<br />
Designing <strong>and</strong> In-vitro studies <strong>of</strong><br />
Gastric floating <strong>tablets</strong> <strong>of</strong> Tramadol<br />
Hydrochloride. International<br />
Journal <strong>of</strong> Applied Pharmaceutics<br />
2010; 2(4): 12-16.<br />
7. Indian Pharmacopoeia (2010) :<br />
Ministry <strong>of</strong> Health <strong>and</strong> Family<br />
Welfare, Government <strong>of</strong> India,<br />
Controller <strong>of</strong> Publication, New<br />
Delhi, India.<br />
8. Uma Maheswari A, Elango K,<br />
Daisy Chellakumari, Saravanan K,<br />
Anglina Jeniffer Samy.<br />
Formulation <strong>and</strong> Evaluation <strong>of</strong><br />
Controlled Porosity Osmotic<br />
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INTERNATIONAL JOURNAL OF<br />
RESEARCH ARTICLE<br />
PHARMACEUTICAL INNOVATIONS ISSN 2249-1031<br />
Tablets <strong>of</strong> Lornoxicam. IJPSR<br />
2012; 3(6): 1625-1631.<br />
9. Vikas Jain, Ranjit Singh.<br />
Dicyclomine loaded Eudragit based<br />
Microsponge with potential for<br />
Colonic Delivery: Preparation <strong>and</strong><br />
Characterization. Tropical Journal<br />
<strong>of</strong> Pharmaceutical Research 2010;<br />
9(1): 67-72.<br />
10. Manoj Kumar Mishra, Mukesh<br />
Shikhri, Rishikesh Sharma,<br />
Mahesh Prasad Goojar.<br />
Optimization, <strong>formulation</strong><br />
development <strong>and</strong> characterization<br />
<strong>of</strong> Eudragit RS 100 loaded<br />
Microsponges <strong>and</strong> subsequent<br />
colonic delivery. IJDDHR 2011;<br />
1(1): 8-13.<br />
Table 1: Composition <strong>of</strong> Lornoxicam <strong>microsponge</strong> containing eudragit RS 100<br />
Ingredient M 1 M 2 M 3 M 4 M 5<br />
Lornoxicam(g) 0.1 0.3 0.5 0.7 0.9<br />
Eudragit RS 100 (g) 0.1 0.1 0.1 0.1 0.1<br />
Polyvinyl Alcohol (g) 0.5 0.5 0.5 0.5 0.5<br />
Triethyl citrate (ml) 0.5 0.5 0.5 0.5 0.5<br />
Ethanol (ml) 5 5 5 5 5<br />
Water (ml) 200 200 200 200 200<br />
Table 2: Composition <strong>of</strong> Lornoxicam <strong>tablets</strong><br />
Formulation<br />
code<br />
Lornoxicam<br />
<strong>microsponge</strong>s (mg)<br />
Micro crystalline<br />
cellulose (mg)<br />
Magnesium<br />
stearate (mg)<br />
Talc<br />
(mg)<br />
Lactose<br />
(mg)<br />
F1 16.00 30 5.4 9 119.60<br />
F2 10.66 30 5.4 9 124.94<br />
F3 9.60 30 5.4 9 126.00<br />
F4 9.14 30 5.4 9 126.45<br />
F5 8.88 30 5.4 9 126.72<br />
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Table 3: Micromeritic properties <strong>of</strong> Lornoxicam <strong>and</strong> powder blend<br />
Drug <strong>and</strong><br />
Blends<br />
Bulk density*<br />
(g/ml)<br />
Tapped<br />
density* (g/ml)<br />
Compressibility<br />
index* (%)<br />
Hausner’s<br />
ratio*<br />
Angle <strong>of</strong><br />
repose*<br />
Drug 0.312±0.012 0.454±0.014 31.2±0.16 1.452±0.06 47.57˚±0.34<br />
MB1 0.51±0.006 0.585±0.004 12.82±0.21 1.14±0.03 30.2˚±0.19<br />
MB2 0.489±0.002 0.560±0.003 12.67±0.24 1.14±0.07 29.7˚±0.69<br />
MB3 0.479±0.003 0.534±0.006 10.29±0.28 1.11±0.05 31.16˚±0.68<br />
MB4 0.489±0.005 0.560±0.008 12.67±0.34 1.14±0.09 30.1˚±0.83<br />
MB5 0.492±0.04 0.558±0.017 11.82±0.19 1.13±0.05 29.11˚±0.20<br />
* Mean <strong>of</strong> three readings<br />
Table 4: Evaluation <strong>of</strong> Lornoxicam <strong>microsponge</strong>s<br />
Formulation Production yield (%) Loading efficiency (%) Mean particle size (µm)<br />
M1 69.35 89.25 75.60<br />
M2 79.3 90.00 64.20<br />
M3 84.77 93.38 62.20<br />
M4 78.20 96.95 54.40<br />
M5 89.65 96.39 45.50<br />
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% DRUG RELEASE<br />
INTERNATIONAL JOURNAL OF<br />
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PHARMACEUTICAL INNOVATIONS ISSN 2249-1031<br />
Table 5: Physical <strong>evaluation</strong> <strong>and</strong> drug content<br />
Formu<br />
-lation<br />
Uniformity<br />
<strong>of</strong> weight *<br />
Diameter<br />
# (mm)<br />
Thickness<br />
# (mm)<br />
Hardness#<br />
(kg/cm 2 )<br />
Friability<br />
^ (%)<br />
Drug<br />
content #<br />
Uniformity<br />
<strong>of</strong> content ҂<br />
Disintegration<br />
time # (min)<br />
(g)<br />
(%w/w) (%w/w)<br />
F1 0.179± 8±0.0 2.5±0.0 4.4±0.45 0.44± 100.6±0.02 100.69±0.52 2.12±0.06<br />
0.006<br />
0.023 3<br />
3<br />
F2 0.179± 8±0.0 2.5±0.0 4.25±0.25 0.47± 96.38±0.05 100.60±1.07 2.19±0.05<br />
0.005<br />
0.012 4<br />
6<br />
F3 0.180± 8±0.0 2.5±0.0 4.75±0.25 0.60± 91.22±0.01 96.85±0.859 2.78±0.01<br />
0.002<br />
0.025 8<br />
F4 0.181± 8±0.0 2.5±0.0 4.25±0.25 0.53± 93.09±0.03 100.7±0.632 2.52±0.05<br />
0.003<br />
0.019 2<br />
F5 0.178± 8±0.0 2.5±0.0 4.35±0.33 0.47± 95.9±0.027 99.76±0.927 3.0±0.02<br />
0.005<br />
0.015<br />
*mean <strong>of</strong> 20 readings. # mean <strong>of</strong> 5 readings. ^mean <strong>of</strong> 3 readings. ҂mean <strong>of</strong> 6 readings<br />
120<br />
100<br />
80<br />
60<br />
40<br />
20<br />
F1<br />
F2<br />
F3<br />
F4<br />
F5<br />
0<br />
0 2 4 6 8 10 12 14<br />
TIME IN HOURS<br />
Figure1: Release study <strong>of</strong> various <strong>formulation</strong>s<br />
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Table 6: Effect <strong>of</strong> stirring rate on Lornoxicam <strong>microsponge</strong>s<br />
Formulation Internal phase composition External<br />
phase<br />
Stirring<br />
rate<br />
Production<br />
yield (%)<br />
Drug Polymer Ethanol water PVA<br />
(rpm)<br />
(g) (g) (ml)<br />
(%)<br />
F5 0.9 0.1 5 200 0.5 200 80.07<br />
0.9 0.1 5 200 0.5 300 75.18<br />
0.9 0.1 5 200 0.5 400 73.96<br />
Mean<br />
particle<br />
diameter<br />
* (µm)<br />
59.67±<br />
3.15<br />
48.19±<br />
6.89<br />
35.81±<br />
4.56<br />
%Drug<br />
content<br />
*<br />
84.17±<br />
1.3<br />
90.02±<br />
2.4<br />
94.23±<br />
1.7<br />
* Mean <strong>of</strong> 5 readings<br />
Table 7: Effect <strong>of</strong> internal phase composition on Lornoxicam <strong>microsponge</strong>s<br />
Formulation Internal phase composition External<br />
phase<br />
Stirring<br />
rate<br />
Production<br />
yield (%)<br />
Drug Polymer Ethanol water PVA<br />
(rpm)<br />
(g) (g) (ml)<br />
(%)<br />
F5 0.9 0.1 5 200 0.5 300 79.29<br />
0.9 0.1 10 200 0.5 300 68.34<br />
0.9 0.1 15 200 0.5 300 66.85<br />
* Mean <strong>of</strong> 5 readings<br />
Mean<br />
particle<br />
diameter<br />
* (µm)<br />
45.5±<br />
5.39<br />
41.99±<br />
6.89<br />
38.25±<br />
7.24<br />
%Drug<br />
content<br />
*<br />
93.95±<br />
1.6<br />
86.21±<br />
0.9<br />
80.05±<br />
0.5<br />
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Log Cum % Drug Remaining<br />
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Table 8: Effect <strong>of</strong> emulsifying agent on Lornoxicam <strong>microsponge</strong>s<br />
Formulation Internal phase composition External<br />
phase<br />
Stirring<br />
rate<br />
Production<br />
yield (%)<br />
Drug Polymer Ethanol water PVA<br />
(rpm)<br />
(g) (g) (ml) (ml) (%)<br />
F5 0.9 0.1 5 200 0.25 300 82.3<br />
0.9 0.1 5 200 0.5 300 78.69<br />
0.9 0.1 5 200 0.75 300 69.05<br />
* Mean <strong>of</strong> 5 readings<br />
Mean<br />
particle<br />
diameter<br />
* (µm)<br />
46.49±<br />
7.11<br />
50.17±<br />
6.45<br />
66.25±<br />
5.67<br />
%Drug<br />
content<br />
*<br />
92.81±<br />
0.8<br />
90.23±<br />
0.4<br />
85.87±<br />
0.6<br />
2.5<br />
2<br />
1.5<br />
y = -0.115x + 2.057<br />
R² = 0.994<br />
1<br />
0.5<br />
0<br />
0 2 4 6 8 10 12<br />
Time<br />
Figure 2: A plot <strong>of</strong> First order kinetics<br />
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Cube root <strong>of</strong> % drug remaining<br />
INTERNATIONAL JOURNAL OF<br />
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5<br />
4.5<br />
4<br />
3.5<br />
3<br />
2.5<br />
2<br />
1.5<br />
1<br />
0.5<br />
0<br />
y = -0.266x + 4.628<br />
R² = 0.991<br />
0 2 4 6 8 10 12 14<br />
Time in Hours<br />
Figure 3: A plot <strong>of</strong> Hixson-Crowell kinetics<br />
Figure 4: SEM image <strong>of</strong> Lornoxicam Microsponges<br />
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