LORXNOXICAM is an NSAIDs and having short duration of half life. The transdermal gel was prepared by incorporating lornoxicam loaded microparticles into a stablized gel base.
Top Quality Call Girl Service Kalyanpur 6378878445 Available Call Girls Any Time
Microparticles Loaded Gel Drug delivery system of Lornoxicam for the Effective Treatment of Rheumatoid Arthritis
1. MICROPARTICLES LOADED GEL OF LORNOXICAM FOR THE
EFFECTIVE TREATMENT OF RHEUMATOID ARTHRITIS
FOR THE DEGREE OF
MASTER OF PHARMACY IN PHARMACEUTICS
BY
R. K VIDYARTHI
B. Pharm.
DEPARTMENT OF PHARMACEUTICAL SCIENCES
FACULTY OF TECHNOLOGY
KUMAUN UNIVERSITY, BHIMTAL CAMPUS, BHIMTAL
2. INTRODUCTION
Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory
autoimmune disease associated with articular, extra-articular and
systemic effects.
RA results in the inflammation of joint tissue, followed by
progressive destruction of bone and cartilage, usually accompanied
by pain, swelling and stiffness.
It may be caused by infection, trauma, degenerative changes,
metabolic disturbances, or other causes.
4. CURRENT AIMS OF TREATMENT
Slow the rate of disease progression.
Control inflammation and pain.
Design appropriate treatment regimen for each patient.
Regular appointments with the clinic and the rheumatologist.
Regular patient monitoring
Monitor patient compliance.
6. C. Biological response modifiers
TNFα inhibitors:
Etanercept,
Adalimumab,
Infliximab
IL-1 antagonist :
Anakinra
D. Corticosteroids and others
Cortisone
Dexamethasone
Hydrocortisone
Methylprednisolone
Prednisone
Prednisolone
Cont…
7. TRANSDERMAL DRUG DELIVERY
Topically administered dosage forms designed to deliver a
therapeutically effective amount of drug across a patient’s
skin.
Provide continuous drug infusion through an intact skin
Developed for topical application onto the intact skin surface
to control the delivery of drug.
Also control subsequent permeation through the skin tissue.
8. Advantages
Bypasses the first pass metabolism
Avoids inactivation of drugs by pH effects and enzymes
present in GI tract
Sustains therapeutic drug levels.
Permits self-administration.
Non-invasive
Avoiding the fluctuation in plasma level of drug.
9. Disadvantages
Only potent drugs are suitable candidates for transdermal
delivery.
Local irritation at the site of application.
May cause allergic reactions.
Molecular weight less than 500 Da is essential.
Sufficient aqueous and lipid solubility, a log P value between
1 and 3 is required for permeation.
10. MICROPARTICLES LOADED GEL
Colloidal drug carriers in the micro- & submicron range.
Overcome solubility problems of poorly soluble drugs.
Contains the active ingredient, is applied to the skin or the mucus
membranes.
Gels are typically prepared from-
liquid phase that has been thickened with other components.
The continuous phase allows free diffusion of molecules through
the polymer matrix.
11. MICROPARTICLES
Microparticles are small spherical particles, with diameters in
the micrometer range (1 μm to 200 μm).
Manufactured from various natural and synthetic polymers
which are biodegradable in nature.
In microparticles drug is dispersed throughout the particle
internal structure is a matrix of drug and polymeric
excipients.
12. Approach
Alternatives to route of administration
At present two dosage forms of lornoxicam are available i.e. tablets
and injections for oral and parenteral administration.
By oral route
Oral route in many instances has side effects associated with
NSAIDs such as gastric bleeding, heartburn, epigastric pain,
ulceration, hepatic dysfunction, etc.
The existing oral dosage form tablet also undergoes first pass
metabolism that results decrease in bioavailability and has poor
aqueous solubility.
13. Cont…
By parenteral route
Although, parenteral dosage forms are available but in case of
chronic therapy or longer treatment this route is not suitable as
parenteral route require invasive techniques.
As in rheumatoid arthritis pain is localized in certain part of body
such as joints & cartilage thus topical route may be more preferable
than other.
Route selected
Topical route has been selected to deliver the microparticulated gel
of Lornoxicam transdermally.
14. Alternatives to dosage form
To Reduce Dosing Frequency
Lornoxicam is a short half-life oxicam hence, two or more dosing
frequency required in a day. The dosing frequency can be
minimized by preparing its controlled release dosage form.
To improve Bioavailability
Penetration of drug into the vicinity of effected area through topical
route bypass the liver, hence no prehepatic metabolism occur and
effect can be maximized.
Cont…
15. Cont…
To improve solubility
by preparing microparticles the particle size is reduced to micron
range that will improve the solubility of drug.
Dosage form selected
Microparticulate topical gel has been chosen as dosage form to
improve solubility, bioavailability and to reduce dosing frequency.
Drug selected
Lornoxicam- it readily penetrates into synovial fluid, the proposed
site of action in rheumatoid arthritis.
16. DRUG PROFILE
Drug Name – LORNOXICAM
Molecular Formula - C13H10Cl N3O4S2
Molecular Weight - 371.8 da.
Chemical Structure –
IUPAC Name - 6-Chloro-4-hydroxy-2-methyl-N-2-pyridyl-2Hthieno[2,3-e]
[1,2]-thiazine-3- carboxamide 1,1-dioxide.
Description - yellow crystalline powder
Category – analgesic, anti-inflammatory and anti-rheumatic ( NSAID )
17. Melting point- 225 -230 0 C
pKa value- 4.7
Partition coefficient – 1.8
Solubility- Lornoxicam is slightly soluble in chloroform and very slightly
soluble in methanol and acetonitrile and hardly soluble in water.
Distribution- readily penetrates into synovial fluids
Metabolism – Hepatic
Oral Bioavailability- 60- 75%
Elimination half-life – 3 to 4 hrs
Excretion – faeces and urine.
18. Literature Review
Buritova J. et al., (1997) evaluated the anti-inflammatory effects of Lornoxicam in the
carrageenan model of inflammatory nociception. Lornoxicam drug was preadministered in both
peripheral oedema and C-FOS protein. In the study they found that lornoxicam reduces
inflammation in both the carrageenan evoked oedema and spinal C-FOS expression.
Jonathan H. et al., (2000) conducted an analysis to show the penetration for the selection of non
steroidal anti-inflammatory agents through the skin. They suggested that the bio-effectiveness of
the NSAIDs will be a function of both its penetration through the skin and its potency. They also
suggested that the pKa will be an important determination in ionization and hence penetration.
Zhang Y. et al., (2005) investigated the pharmacokinetics of lornoxicam and the relationship
with CYP2C9 polymorphism in healthy Chinese subjects. A single oral dose of 8 mg lornoxicam
was administered to 18 healthy male subjects. Plasma sample was taken after 24 hr and drug was
measured using a validated analytical method. The results showed that the pharmacokinetics of
lornoxicam is dependent on CYP2C9 polymorphism and the presence of CYP2C9 allele
impaired the oral clearance of lornoxicam.
Sankar V. et al., (2005) formulated ophthalmic gel of diclofenac sodium by using polymers
sodium alginate, sodium CMC and hydroxyl propyl methyl cellulose (HPMC) in different
concentrations. The in-vitro release studies of different gel formulations after 9 hours was
expressed in decreasing order as follows HPMC gel>Methylcellulose gel>sodium CMC gel. The
results showed that diclofenac formulations were found to be more stable in HPMC gel
compared to methyl cellulose gel and sodium CMC gel.
19. Cont….
Ramchandani U. et al., (2011) have designed transdermal therapeutic systems to provide
controlled continuous delivery of drugs via the skin to the systemic circulation. NSAIDs are an
excellent drug for transdermal delivery. Furthermore, topical administration via the dermal route
can bypass disadvantages of the oral route. Therefore, transdermal drug delivery has been
considered to be an ideal route for administration of NSAIDs.
Selvaraj S. et al., (2012) had prepared transdermal gel of chitosan loaded microspheres for
ocular delivery of acyclovir as eye ointment. Acyclovir loaded microparticles gel showed better
results for effective management of ocular viral infections.
Karthikeyan K. et al., (2012) formulated a bioadhesive carbomer gel incorporated drug loaded
gelatin microspheres for periodontal therapy. The microspheres incorporated carbomer gel was
found to be potential delivery system for the treatment of inflammation and infection in
periodontitis. The formulated microspheres also showed good drug loading, sustained release of
diclofenac and metronidazole hydrochloride for more than 4 hours.
Baviskar D.T. et al., (2013) developed diclofenac sodium gel using carbopol 934P and high
molecular weight hydroxyl methylcellulose for topical and systemic delivery. Results showed
that diclofenac sodium gel containing HPMC, carbopol 934p and carbopol as permeation
enhancer exhibited good anti-inflammatory activity and systemic delivery.
Jayaraja K. et al., (2014) prepared microspheres loaded topical gel delivery system of
ketoconazole an antifungal medication. The prepared microspheres were incorporated into gel
and evaluated for drug release study. Microparticulate loaded topical gel exhibited maximum gel
strength, highest value of mucoadhesion force and remarkable spreadability.
20. Cont….
Nief R.A et al., (2014) developed gel formulation of microsponges of poorly soluble drug
meloxicam (MLX) in order to enhance the release and dissolution of MLX which is the
limitation for preparation in topical forms. The results showed that the microsponge formula
had optimum physical properties and enhanced the dissolution rate of MLX. MLX
microsponge carbopol gel produced a significant improvement of the in vitro release than pure
MLX gel.
Kaur L. et al., (2014) prepared transdermal gel of meloxicam, an oxicam derivative. They
used permeation enhancers and polymers for increasing the drug permeation rate. Polymers,
carbopol 940 and HPMC were used in different concentration in topical gel formulation. Their
in-vitro drug release study showed that the maximum drug permeation through the cellophane
membrane produced by HPMC formulation as compared to carbopol-940.
Habib F. et al., (2011) prepared mucoadhesive buccal patches of lornoxicam using different
polymers and performed in-vivo evaluation and clinical efficacy of patches. The in-vivo animal
experiment showed that lornoxicam formulated in different buccal patches was successfully
delivered to the systemic circulation and showed high absolute bioavailability of lornoxicam.
Karthika R. et al., (2013) formulated and evaluated lornoxicam microsponge tablets for the
treatment of arthritis. Microsponges containing Lornoxicam and Eudragit RS100 were
prepared by quasi emulsion solvent diffusion method. In-vitro dissolution studies showed that
the release rate of Lornoxicam was found to be enhanced
21. Avachat A.M. et al., (2013) carried out permeation study using freshly excised rat skin. Anti-
inflammatory activity of lornoxicam gel was studied in albino Wistar rats and compared with
the marketed formulation of piroxicam (Pirox® gel). In their result they found that optimized
formulation containing 2 % of transcutol P as permeation enhancer gave higher drug release
than other penetration enhancers.
Gulzar A. et al., (2015) developed lornoxicam transdermal gel and its iontophoretic delivery to
enhance its permeation for systemic effect and to avoid side effects and minimize frequency of
administration. They formulated physiochemically stable and non-irritant Lornoxicam gel which
could deliver significant amount of active substances across the skin in-vitro and in-vivo which
elicit the anti-inflammatory activity.
Jain V. et al., (2015) prepared epicutaneous gel of lornoxicam to facilitate the controlled release
of active drug into the skin in order to reduce the systemic exposure and to minimize local
cutaneous reactions of active drug. From their study they concluded that formulated
epicutaneous gel of lornoxicam shows drug release in a controlled manner using micro sponge
technology.
Cont….
22. AIM AND OBJECTIVE
AIM
The aim of the study was formulation and evaluation of microparticulated gel
drug delivery system of lornoxicam for the effective treatment of rheumatoid
arthritis.
OBJECTIVES
The objective of this work was to develop an effective topical preparation for
enhancing drug bioavailability in effected area, improving drug solubility and
controlled release of medication.
To perform preformulation studies for the selection of preparation
techniques.
To overcome potential side effects of the drug and enhance its therapeutic
effectiveness.
To formulate microparticles by using different drug polymer ratios.
Incorporation of microparticles into gel base and its evaluation.
To conduct in-vitro drug release of prepared microparticulated gel.
23. 1. LITERATURE REVIEW
2. SELECTION OF MATERIALAND EXCIPIENTS
3. PREFORMULATION STUDIES
Drug Identification
• Physical examination
• Melting Point
• UV Spectroscopy
Drug Solubility
Calibration Curve
Partition Coefficient
Compatibility Study with Excipients (FTIR)
4. PREPARATION OF MICROPARTICLES
5. EVALUATION OF MICROPARTICLES
PLAN OF WORK
24. Percentage yield
Particle size and shape determination
Drug content
Percentage drug entrapment
Drug release of microparticles
6. FORMULATION OF MICROPARTICULATE GEL
Preparation of Gel base
Incorporation of microparticles into gel base
7. EVALUATION OF MICROPARTICULATE GEL
Physical examination
Viscosity determination
pH determination
Spreadability
Drug content
Drug release/diffusion studies
8. SUMMARY AND CONCLUSION
Cont…
25. MATERIALS
S. No. Chemical name Supplier of materials
1 Lornoxicam Yarrow Chem. Pvt. Ltd, Mumbai
2 Ethyl cellulose CDH Laboratory Reagents, New Delhi
3 Eudragit RS 100 Otto chemicals
4 HPMC K15M Molychem, India
5 Chloroform Molychem, India
6 Tween 80 Lobachemie, India
7 Potassium dihydrogen phosphate CDH Laboratory Reagents, New Delhi
8 Di-sodium hydrogen phosphate CDH Laboratory Reagents, New Delhi
9 Sodium Chloride CDH Laboratory Reagents, New Delhi
Various chemicals used along with their source
26. Various instruments used along with their manufacturer
S. No Instrument Manufacturer
1 Digital Weighing Balance Biogen, Model PBG200
2 Hot air oven Hicon industries, Delhi
3 Magnetic stirrer Remi Equipment Ltd. Mumbai
4 Mechanical stirrer Remi Equipment Ltd. Mumbai
5 Melting point apparatus U-Tech
6 UV-VIS spectrophotometer Shimadzu 1601, Corporation, Japan
7 Digital pH-Meter Elico, India
8 Dissolution Apparatus Electrolab
9 Microscope Leica Digital Photomicroscope
10 Viscometer Brookfield DV-E-Viscometer
11 KC diffusion cell Orchid Science & Innovative Ind. P.Ltd
27. FORMULATION METHOD OF MICROPARTICULATED GEL
Preparation Of Microparticles
Prepared by the emulsion solvent evaporation method.
The drug and polymers were dissolved in 15 ml of chloroform.
Aqueous phase of 100 ml was prepared in distilled water containing 0.5 % Tween 80 as an emulsifier.
Then organic phase was added to the aqueous phase drop wise with continuous stirring at 2000 rpm.
The formed o/w emulsion was stirred continuously until complete evaporation of chloroform;
the microparticles were filtered washed with excess of distilled water and dried at room temperature in a
desiccator..
S. No Formulation
code
Lornoxicam
(mg)
Ethylcellulose
(mg)
Eudragit RS100
(mg)
1 FM1 200 200 200
2 FM2 200 400 200
3 FM3 200 200 400
4 FM4 200 400 400
5 FM5 200 600 200
6 FM6 200 200 600
28. Cont…
Preparation of Gel Base
- not good, + good, ++ better, +++ best
Method: Required amount of gelling agent was weighed and this was sprinkled over
distilled water very slowly for an hour with moderate agitation. This thickened
solution was allowed to stand overnight for proper swelling and wetting of each
particles of gelling agent.
The gel base for final formulations was prepared using 2% w/v concentration of
HPMC K15M in distilled water as it showed good characteristics of a gel base.
Gelling agent Strength Clarity Homogeneity Consistency Appearance
Carbopol 934 p
0.5% + + Less hazy
1% + + Less hazy
1.5% - + Moderate turbid
HPMC K15M
1% +++ +++ Less clear
2% +++ +++ Moderate clear
3% ++ +++ More clear
Tragacanth
2.5% ++ ++ Less translucent
5.0% ++ ++ Moderate translucent
7.5% + ++ More turbid
29. Cont…
Incorporation of Microparticles Into Gel Base
Microparticles equivalent to 200 mg of drug were weighed and incorporated
into the gel base to prepare a gel of 0.2 % w/w final concentration of drug.
Prepared microparticles were dispersed into the gel base and other excipients
such as tween 80, methyl paraben were dissolved in ethanol and added to the
gel base.
Tri-ethanolamine was used to adjust the pH of microparticulated gel system.
S. No. Ingredients Quantity (% w/w)
1 LRN microparticles 200 mg
2 HPMC K15M 2.00 gm
3 Ethanol 10 ml
4 Methyl paraben 40 mg
5 Tween 80 1 gm
6 Tri-ethanolamine (5%) q.s
7 Distilled water (q.s) 100 gm
30. RESULTS AND DISCUSSION
PREFORMULATION STUDIES
Physical examination:
Melting point: 226 °C ± 1 °C (n=3).
Determination of λ max (absorption maxima): The observed λ max was
found to be at 376 nm.
UV spectrum of lornoxicam
Properties Results
Description Crystalline powder
Colour Yellow
Odour Characteristics
Taste Bitter
31. SOLUBILITY STUDIES
Results of solubility studies in different solvents
Calibration curve of lornoxicam in phosphate buffer pH
7.4
The calibration curve of lornoxicam in phosphate buffer pH
7.4 was determined in the conc. range of 4-20 µg/ml.
Solvents
Solubility
(gm/ ml)
Scale of
Solubility
D.Water 0.009
Very slightly
soluble
PBS pH 7.4 0.405 Freely soluble
Acetone 0.304
Sparingly
soluble
Chloroform 0.739 Freely soluble
Methanol 0.052 Soluble
Ethanol 0.072 Soluble
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Solubility(g/ml)
Solvents
32. CALIBRATION CURVE OF LORNOXICAM IN PHOSPHATE BUFFER PH 7.4
S. No. Concentration
(µg/ml)
Absorbance
1 4 0.1769
2 8 0.3478
3 12 0.5044
4 16 0.6426
5 20 0.8002
Parameters Lornoxicam
λmax (nm) 376
Correlation coefficient 0.998
Slope (m) 0.039
Intercept (C) 0.015
Straight line equation y=0.039x+0.015
y = 0.039x + 0.015
R² = 0.998
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
0 4 8 12 16 20
Absorbance
Concentration (µg/ml)
Absorbance
Solvent
system
Conc. of
drug in oil
phase
Conc. of
drug in
aqueous
phase
Partition
coefficient
(log p)
n-octanol/
PBS pH
7.4
18.015
µg/ml
9.869
µg/ml
1.8
Partition Coefficient
36. OPTICAL MICROSCOPY
This was done with the help of Leica Digital Photomicroscope. The images are shown below:
Digital microscope photograph of microparticles
42. Drug Content Of Lornoxicam Gel
In-vitro Drug Release Of Lornoxicam Gel
In-vitro drug release studies were performed using a Keshary-Chien diffusion
cell with a receptor compartment capacity of 25 ml. The whole assembly was
fixed on a magnetic stirrer, and the solution in the receptor compartment was
constantly and continuously stirred using magnetic beads at 50 rpm; the
temperature was maintained at 37 ± 0.50 °C.
S. No. Formulation code % drug content (mean±SD)
1 FG1 84.24 ± 1.22
2 FG2 93.25 ± 0.74
3 FG3 87.63 ± 1.54
4 FG4 95.02 ± 1.79
5 FG5 98.79 ± 0.55
6 FG6 86.07 ± 2.20
50
60
70
80
90
100
GF1 GF2 GF3 GF4 GF5 GF6
%DrugContent
Formulations
43. In-vitro Drug Release of Microparticulated gel of Lornoxicam
S.
No
.
Time
(in
hours)
% Cumulative drug release
FG1 FG2 FG3 FG4 FG5 FG6
1 0 0 0 0 0 0 0
2 0.25 2.23 3.06 0.219 4.39 2.63 1.15
3 0.5 8.79 7.71 4.31 16.48 13.01 4.77
4 1 16.16 12.99 11.62 26.25 25.1 9.95
5 2 24.11 19.88 20.25 32.96 39.11 15.46
6 3 29.14 26.95 25.85 39.68 54.79 19.9
7 4 35.28 33.49 31.63 53.66 69.06 27.23
8 5 44.1 37.66 41.68 66.42 78.44 34.43
9 6 49.72 40.08 49.1 75.03 80.92 39.28
10 7 55.46 42.45 55.39 83.76 83.94 45.05
11 8 60.53 44.87 61.46 86.2 87.37 49.67
12 9 65.46 49.21 67.5 88.76 90.08 53.18
13 10 71.72 55.21 72.36 90.96 92.68 55.97
14 11 77.7 58.72 74.7 93.28 95.16 58.97
15 12 80.62 62.03 76.62 95.84 96.68 60.87
0
10
20
30
40
50
60
70
80
90
100
0 1 2 3 4 5 6 7 8 9 10 11 12
%Cumulativedrugrelease
Time (in Hours)
FG1
FG2
FG3
FG4
FG5
FG6
Formu
lation
Zero
order
First
order
Higuchi
matrix
Peppa
s plot
Baker
Lonsdale
‘n'
value
Best Fit
model
FG1 0.859 0.993 0.966 0.909 0.991 0.808 First order
FG2 0.958 0.986 0.990 0.981 0.963 0.712
Higuchi
matrix
FG3 0.979 0.993 0.972 0.883 0.951 1.235 First order
FG4 0.922 0.981 0.987 0.947 0.978 0.707
Higuchi
matrix
FG5 0.981 0.983 0.986 0.961 0.935 0.813
Higuchi
matrix
FG6 0.977 0.996 0.976 0.968 0.970 0.934 First order
Model fitting release profile of formulation FG1 to FG6
44. SUMMARY
A successful attempt was made to formulate six microparticulated gel
formulations of lornoxicam using combination of two polymers viz.
ethylcellulose & eudragit RS 100 in different ratio, and HPMC K15M was used
as gel base.
In preformulation studies showed that the drug was found to be yellow
crystalline powder, bitter in taste and observed melting point of lornoxicam was
found to be 226 0C. The solubility studies showed that the drug was very soluble
in chloroform and very slightly soluble in water.
The partition coefficient of Lornoxicam was found to be 1.8. The UV
spectrograph of drug following Lambert-Beer’s Law from 4 to 24 mcg/ml range
in phosphate buffer pH 7.4, the eq. was found to be Y=0.039x+0.015 with r2=
0.998 value.
FTIR spectroscopy showed that there is no interaction between drug and
polymers.
45. Cont….
The drug content of microparticle formulations was found to be in the range of 74.26
to 98.67%.
The prepared gels of lornoxicam were then subjected to various evaluation
parameters such as physical examination, viscosity, spreadability, drug content and
In-vitro drug release study were determined for all formulations.
The microparticulated gel prepared by HPMC K15M showed good rheological
properties, clarity, spreadability, transparency and extensive release property of drug
from microparticles.
Among the different microparticles loaded gel formulations of lornoxicam, the
formulation FG4 and FG5 were selected as the best formulations on the basis of their
various evaluation parameters and in-vitro drug diffusion studies conducted up to 12
hours.
46. CONCLUSION
Lornoxicam is an effective drug in the management of arthritic conditions. As it has
extensive property of distributing in more amounts in synovial fluid, hence provide better
concentration in joints and cartilages as required treating the arthritic conditions.
Lornoxicam has good physicochemical properties that suits it better candidate for
transdermal drug delivery.
Microparticles loaded gel formulations were good in appearance and were also in the
suitable pH range. The in-vitro diffusion studies revealed that the drug release was
acceptable with the formulations. Among the different microparticles loaded gel
formulations of lornoxicam, the formulation FG4 and FG5 were selected as the best
formulations.
This study confirms that the emulsion solvent evaporation technique is suitable for
preparation of microparticles of lornoxicam with acceptable drug content and drug release
profile. The method of preparation of microparticulated gel was simple and reproducible.
The developed formulation overcomes and removes the shortcomings of the conventional
dosage forms of lornoxicam currently used, which is much needed in this age of
advancement and development.
47. Budhathoki U., Thapa P., “Effect of chemical enhancers on in-vitro release of
salbutamol sulphate from transdermal patches”, Kathmandu university J of
science, engineering and technology, 2005; 1(1):1-8.J
Jain D., Maithani M., Mishra S.K., Khare P., Jain V., “Development and
characterization of dutasteride bearing liposomal systems for topical use”, Curr.
Drug Discov. Technol., 2011; 8: 136-45.
Kataria S., Middha A., Sandhu P., Bilandi A., Kapoor B., “Microsphere: A
Review”, International Journal of Research In Pharmacy And Chemistry, 2011;
1(4): 1184-98.
Nikam V.K., Gudsoorkar V.R., Hiremath S.N., Dolas R.T., Kashid V.A.,
“Microspheres A Novel Drug Delivery System: An Overview”. International
journal of pharmaceutical and chemical sciences, 2012; 1(1): 113-28.
Kumar J.R., Muralidharan S., “Development of Microparticle Loaded Gel
(MPLGs) for Prolong Ocular Drug Delivery Containing Ketorolac
Tromethamine”, J. Pharm. Sci. & Res., 2014; 6(3): 148-52.
REFERERNCES
48. Sweetman S.C., “Martindale: The complete Drug Reference”, Pharmaceutical
Press, London; 36th edition; 2006: 77.
“Indian Pharmacopoeia”, Indian Pharmacopoeia commission, Ghaziyabaad; 7th
edition; 2014; 1:190.
Hitzenberger G., Welte S.R., Takacs F., Rosenow D., “Pharmacokinetics of
lornoxicam in man”, Postgrad. Med. J., 1990; 66(4): 22-26.
Buritova J., Besson J.M., “Potent anti-inflammatory/analgesic effects of
lornoxicam in comparison to other nsaids: A c-fos study in the rat”, Inflammo
Pharmacology1997; 5(4): 331-341.
Jonathan H., Jeanetta D.P., Colleen G., “The selection of non-steroidal anti
inflammatory agents for dermal delivery”, Int. J. Pharm., 2000; 207: 31-37.
Mauro B., Alberto E.P., “Effects of lornoxicam, piroxicam, and meloxicam in a
model of thermal hindpaw hyperalgesia induced by formalin injection in rat tail”,
Pharmacol. Res., 2002; 45: 101-05.
49. Zhang Y., Zhong D., Dayong S., Yingjie G., Xiaoyan C., “Lornoxicam
pharmacokinetics in relation to cytochrome P450 2C9 genotype”, British Journal
of Clinical Pharmacology, 2005; 59(1): 14-17.
Hamza Y.S., Aburahma M.H., “Design and in vitro evaluation of novel sustained-
release matrix tablets for lornoxicam based on the combination of hydrophilic
matrix formers and basic pH-modifiers”, Pharm. Dev. Technol., 2010; 15(2):139-
53.
Avachat A.M., Mundada M.S., Wankhede S.S., Patwardhan S.K., “Formulation
and Evaluation of Topical Gel of Lornoxicam Using a Range of Penetration
Enhancers”, Ind. J. Pharm Edu. Res., 2013; 47(2): 168-71.
Mishra V.K., Tripathi S.S., “Formulation development and evaluation of
gliclazide gel using water soluble sodium carboxy methyl cellulose polymer”,
Indian Journal of Research in Pharmacy and Biotechnology, 2013; 1(5): 697-700.
50. Sharma V., Parashar B., Chandel A., “Formulation and Evaluation of
Lornoxicam As Mucoadhesive Microcapsules”, Int. J. Pharm., 2013; 3(3): 527-
33.
Srivastava A., Gowda D.V., Ram A.S., Datta V., Hatna S., “Encapsulation of
Lornoxicam into spermaceti microspheres and comparative bioavailability
study”, International Journal of Drug Delivery, (2014); 6: 07-13.
Khadka D., Gulzar M.A., “Formulation and Evaluation of Transdermal Gel of
Lornoxicam in combination with Chemical Enhancers”, IJRPC 2014; 4(4): 996-
1003.
Vikas J., Pandey P., Shukla N., Sisodiya D., “Design and Characteri-zation of
micro sponge loaded controlled release epicutaneous gel of lornoxicam”,
Journal of applied medical research, 2015: 1(1): 16-21.
Singla K., Rao R., Saini V., “Preparation And Evaluation of Lornoxicam Niosomal
Gel”, Int. Res. Journal of Pharmacy, 2012; 3(4): 378-83.