Estimation of topiramate by colorimetric method rohit bharti
project ppt
1. GREEN APPROACH FOR DEVELOPMENT OF ORALLY
DISINTEGRATING TABLETS
Research Student
Kishor V. Kande
(M.Tech)
RESEARCH GUIDE
PROF. P. V. DEVARAJAN
9/16/2016 1
OPEN DEFENCE
INSTITUTEOF CHEMICAL TECHNOLOGY, MUMBAI
2. 9/16/2016 2
INTRODUCTION
According to US FDA:
“A solid dosage form containing medicinal substance, which disintegrates
rapidly usually within a matter of seconds, when placed upon the tongue”.
More rapid drug absorption from the pre-gastric area i.e. mouth, pharynx
Easy administration for patients who are mentally ill, disabled and uncooperative
Improved stability, low sensitivity to environmental condition
No water needed
Increase bioavailability of drug
Definition of Orally Disintegrating Tablets
ODTs
Advantages
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TECHNOLOGIES
CONVECTIONAL
TECHNOLOGIES
Freeze Drying
Tablet Moulding
Direct Compression
Spray Drying
Sublimation
Mass Extrusion
PATENTED
TECHNOLOGIES
Zydis Technology
Orasolve Technology
Durasolv Technology
Wowtab Technology
Flashdose Technology
Flashtab Technology
AdvaTab
Oraquick Technology
Area Wise Distribution of
Technologies used
Conventional Tablet Compression (85%)
Tablet moulding (9%)
Freeze-Drying (4%)
Tablet Loading (1%)
AlHusban, Farhan, Yvonne Perrie, and Afzal R. Mohammed. "Formulation of multiparticulate systems as lyophilised orally disintegrating
tablets." European journal of pharmaceutics and biopharmaceutics 79, no. 3 (2011): 627-634.
4. 9/16/2016 4
LIMITATIONS OF CURRENT
TECHNOLOGY
Limitations
High
Friability
Taste
Masking
Rapid
Disintegra
tion
Moisture
Sensitive
Processing
Time
Cost of
Final
Product
5. AIM, OBJECTIVE AND RATIONALE
9/16/2016 5
To develop microwave assisted orally disintegrating tablets of LMG
with rapid dissolution.
Objective
Develop
Placebo
ODT
Decrease
DT &
Increased
strength
Increase
dissolution
rate of drug
Lamotrigin
ODTs
Taste
Masked
Formulation
6. WHY MICROWAVE TECHNOLOGY FOR
ODT
9/16/2016 6
To make a porous tablet for reducing disintegration time (DT)
Increased hardness with low (DT)
Reduce processing time
Reduction in formulation cost
Process Scalability
Principal Behind Formation of Porous Tablet
Microwave irradiation produces water vapor from the water carrier in wet
molded tablets and could also dissolve the surface of sugar alcohol granules to
form new bridges between particles.
Sano, S., Iwao, Y., Kimura, S., Itai, S., 2011. Preparation and evaluation of swelling induced-orally disintegrating tablets by
microwave irradiation. Int. J. Pharm. 16,252–259.
7. DRUG PROFILE
9/16/2016 7
Parameter Value
Drug Lamotrigine (LMG)
Molecular Wt. 256.1
Mol. formula C9H7Cl2N5
Category Anticonvulsant
Solubility Very slightly soluble in water
Half life 25 +/- 10 hours (healthy
individuals); 42.9 hours
(chronic renal failure )
Log P 2.5
Polar surface area 90.71
Polarizability 23.7
Structure
IUPAC Name: 6
(2,3dichlorophenyl)-1,2,4-
triazine-3,5-diamine
BCS class II (Low solubility
& High permeability)
8. WHY ODT FOR LAMOTRIGINE
9/16/2016 8
Lamotrigine is an anticonvulsant drug indicated for treatment of bipolar I disorder
and for various types of epilepsy
Conventional tablets cannot be given to epilepsy patients, ODT tablets makes
treatment easier for immediate therapeutic action
Difficulty in swallowing (Dysphagia) is a common problem of all age groups,
especially elderly and pediatrics
9. Aim: LMG and LMG + excipients (1:1) compatibility study by FTIR in
presence of microwave irradiation at 490 watt for 5min.
Name Category
Ac-Di-Sol superdisintegrant
Explotab (SSG) superdisintegrant
Crosspovidone superdisintegrant
PVP K-25,30,90 Binder
Pregeletinized starch Binder
DC Lactose Diluent
Avicel (MCC) Diluent
Perlitol-200 (Mannitol) Diluent
Magnesium stearate Lubricant
βCD Complexing agent (For solublization)
HP-βCD Complexing agent (For solublization)
PREFORMULATION STUDY
9/16/2016 9
10. Lamotrigine:
A
B
frequency, cm–1 Bond functional group
A 3400–3250 N–H Stretch 1°, 2° amines
B 1650–1580 N-H Bend 1° amines
C 1335–1250 C-N Stretch Aromatic amines
D 850-550 C-CL Stretch Alkyl halides
E 3500-3200 0-H Stretch Alcohols, phenols
C D
9/16/2016 10
11. 9/16/2016 11
(a) Pure LMG, (b) LMG+Ac-Di-Sol after 24hr., (c) LMG+Ac-Di-
Sol after 1 month, (d) LMG+ SSG after 24hr., (e) ) LMG+ SSG
after 1 month.
(a) Pure LMG , (b) LMG + Crospovidone after 24hr., (c) LMG +
Crospovidone after 1 month., (d) LMG + Mannitol after 24hr., (e) LMG
+ Mannitol after 1 month, (f) LMG + PVP K-25 after 24hr., (g) LMG +
PVP K-25 after 1 month.
(a) Pure LMG, (b) LMG + DC Lactose after 24hr., (c) LMG + DC
Lactose after 1 month, (d) LMG + β-CD after 24hr., (e) LMG + β-
CD after 1 month, (f) LMG + HPβ-CD after 24hr., (g) LMG +HPβ-
CD after 1 month
16. 9/16/2016 16
HPLC METHOD VALIDATION
Precision
Sr. No System precision Method precision
1 892281 896926
2 911213 916932
3 914210 907892
4 891839 904897
5 899837 895789
6 918334 916893
AVG 904619 906554.8
SD 11506.45 9248.971
% RSD 1.271966 1.020233
Precision study for Lamotrigine analysis by HPLC
System and method precision was found to be good (% RSD<2)
LOD and LOQ
The LOD and LOQ concentrations were found to be 0.185 μg/ml and 0.563 μg/ml
respectively.
17. 9/16/2016 17
HPLC METHOD VALIDATION
Stability of analyte in solution
Lamotrigine was found to be stable as a solution in the mobile phase, when the standard
solution of strength 10 μg/ml was analyzed at 0, 6, 24 and 48 hrs. post preparation. No
peaks corresponding to the degradation products were observed and there was no
significant change in the drug peak area. A low %RSD value (1.145) indicated that there
was no significant change in the drug peak areas (%RSD>2).
Specificity
Samples of the placebo formulations revealed clean chromatograms with no interference
from the tablet excipients. The ability of the method to separate the drug from its
degradation products and the non-interference from the tablet excipients indicates the
specificity of the method.
The RP-HPLC method developed was found to be
precise, rapid, specific and stability indicating. The
method enabled good separation of the drug and the
degraded products with a linearity range of 1-10 μg/mL
and an R² of 0.9998 for Lamotrigine (LMG)
20. PREPARATION OF HUMIDITY CHAMBER
To prepare humidity chamber we used salt
solution
60gm of potassium sulphate in 20 ml of
water
Solution is poured in desiccator
It generates above 95 % humidity
Use of salt solutions for assuring constant relative humidity conditions in contained environments , Gonzalo Quincot et al.
PTDC/ECM/099250/2008 – Project Report .
9/16/2016 20
27. 9/16/2016 27
LMG COMPLEX FORMATION
Molecular Modeling
Minimized Macromodel 3D Complex of
LMG-β-CD
(b)
(a) Represents the molecular interactions between LMG and β-CD complex in 1:1 ratio at 0 ns. (b) Represents inclusion complex
of LMG- β-CD after 10ns .The yellow dotted lines indicate hydrogen bond interactions between the amide groups of LMG and
the hydroxyl groups of β-CD
(a)
DFT (density functional Theory) calculation: The aqueous solvation energy was calculated for LMG and LMG-β-
CD complex using DFT calculations. The value of aqueous solvation energy for LMG was found to be -16.92
kcal/mol and for LMG and β-CD complex was -198.89 kcal/mol. The higher negative energy value higher is the
solubility. Therefore it can be concluded that solubility of LMG was enhanced due to complexation with β-CD.
28. 9/16/2016
28
Lamotrigine Solubilization by β-CD and HP-βCD
Continue…..
Phase Solubility studies
y = 0.8099x + 1.0179
R² = 0.9815
0
1
2
3
4
5
6
7
8
9
10
0 5 10 15
DrugconcentrationmM
HP-βCD concentration mM
Stand. curve of LMG in HP-βCD
y = 0.5795x + 0.9912
R² = 0.9768
0
1
2
3
4
5
6
7
8
0 5 10 15
DrugConcentrationmM
βCD Concentration mM
Stand. Curve OF LMG in β-CD
These solubility curves of LMG in the presence of βCD and HP-βCD can be classified as AL
type according to Higuchi and Connors and may be attributed to the formation of soluble 1:1
LMG-βCD and LMG-HP-βCD inclusion complex
The calculated stability constant K1:1 of LMG with β-CD and HP-βCD were 524.72 and
331.81/M respectively, which indicated the cavity size of βCD and HP-βCD is optimal for
entrapment of the LMG molecules and it provides a better solubilization effect
Solubility Constant (K1:1)= Slope / Intercept (1-Slope)
Compexation process was done by the wet kneading method,
by wetting the physical mixture of LMG-β-CD and LMG-
HP-β-CD in the 1:1 molar ratio in a mortar with ethanol and
water mixture (1:1 by volume). Wet mixture was kneaded
thoroughly in a mortar and pestle to obtain a paste like
consistency. The paste was then dried in an oven at 50 0C
temperature, pulverized by passing through sieve no. 60 and
stored in a desiccator till further use
29. 9/16/2016 29
CHARACTERIZATION OF LMG COMPLEX
a) FTIR Spectrophotometry
(a) Pure LMG (b) βCD and (c) IR spectra of LMG- β-CD complex(d)
LMG- HP-β-CD spectra.
b) The X-ray Diffraction study (XRD)
XRD pattern for (a) Lamotrigine and (b) LMG-
βCD complex
XRD spectra of LMG revealed crystalline nature (a). Absence of sharp reflection of LMG in the
complex LMG-βCD (b) suggested partial conversion of crystalline LMG in amorphous form or
decreased crystallinity in complex.
30. 9/16/2016 30
Continue….
c) Differential Scanning Calorimetry (DSC)
Overlay DSC Thermograms of (a) LMG, LMG- βCD complex, (b)
LMG, LMG-HP- βCD
The DSC thermo gram revealed sharp melting
endotherm of LMG at 221 0C. The DSC thermo
gram of prepared complex of LMG-βCD showed
reduced intensity of endothermic peaks and slightly
shifted to lower temperature (a) suggesting
incomplete complexation. Also the complex LMG-
HP-βCD in (b) shows a total reduction of endotherm
which indicated complex formation.
On the basis of
complexation results
decided to go with wet
kneeding method with βCD
and HP-βCD which are
best solubilizing agents for
LMG proved by Phase
solubility study and
complex characterization.
31. 9/16/2016 31
DRUG LOADING IN OPTIMIZED PLACEBO
FORMULATION
Ingredients (mg/tablet) DC20 DC21 DC22 DC23
Complex (equivalent to 25mgLMG ) 135.82 - 135.82 -
Complex (equivalent to 25mgLMG ) - 159.35 - 159.35
DC Mannitol 56.18 56.18 51.18 51.18
Crospovidone 5 5 10 10
PVP k-25 2 2 2 2
Mg. Stearate 1 1 1 1
Tablet wt.(mg) 200 223.53 200 223.53
Hardness(Kg/Cm) Initial 2 2 2 2
After MWT* 2.8 3 2.8 3
30 min Humidity
then MWT*
5.5 6 5.5 6
DT (Second) Initial 129 10min10sec 102 8min10sec
After MWT* 115 8min 90 6 min
30 min Humidity
then MWT*
50 6min30 sec 23 5min 30sec
*Microwave treatment for 3.5 minutes at 490 watt
32. 9/16/2016 32
For lower DT batches DC22 and DC23 were prepared with increased concentration of
crospovidone.
Batch DC22 batch revealed very low DT (23 sec) after MWT, while DC23 comprising
HPβCD showed very high DT greater than 5 minutes with increased hardness when
subjected to MWT .
Hence batch DC22 comprising LMG-βCD complex which gave us very low DT (23 sec.) and
good hardness (5.5) using MWT would be considered for application of factorial analysis, to
arrive at an optimum formulation.
129 115
50
610
480
390
102 90
23
470
360
330
0
1
2
3
4
5
6
7
0
100
200
300
400
500
600
Initial After MWT* 30 min RH then MWT*
Disintegration & Hardness Test (N=3)
DC20 DC21 DC22 DC23 DC20. DC21. DC22. DC23.
Hardness
(kg/cm)
DisintegrationTime
(Seconds)
Batch Conditions
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OPTIMIZATION USING DESIGN OF
EXPERIMENT (DOE)
Application of 23 factorial analyses for evaluation of critical
quality attributes
Factors: Formulation Variables
Levels
-1 +1
A Crospovidone (%) 5 7.5
B Humidity exposer (Min.) 20 40
C Microwave drying (Min) 2 5
Response Target Range
Y1 Disintegration Time (Sec) 15 25
Y2 Hardness(kg/cm) 4 6
34. 9/16/2016 34
Batches designed by design-expert® software (N=3)
Using Design-Expert®7, analysis of critical quality attributes (CQAs) was carried
out by using appropriate models and from that 3FI model finalized as suggested
by the software.
Batch No Run order A:
Crospovidon
e (%)
B:
Microwave
drying (min)
C: Humidity
exposer
(min)
Response 1
DT (Sec)
Response 2
Hardness
(kg/cm)
31 1 2.50 2 20 67. 33 ± 1.52 3.06 ± 0.11
32 2 2.50 5 40 50.66 ±1.15 5.53 ± 0.11
33 3 7.50 5 20 59.66 ± 0.57 6.53 ± 0.05
34 4 7.50 2 20 15 ± 0.1 2.56 ± 0.11
35 5 7.50 5 40 20.66 ± 1.15 5.93 ± 0.11
36 6 7.50 2 40 24.33 ± 0.2 2.6 ± 0.1
37 7 2.50 2 40 80.33 ±0.57 2.53 ± 0.05
38 8 2.50 5 20 110.33 ±
1.52
6.1 ± 0.45
39 9 5 3.50 30 20.66 ± 1.52 5.53 ± 0.05
Continue…
35. 9/16/2016 35
ANOVA RESULT FOR 3FI MODEL FOR RESPONSE DT (Sec)
Source Sum of Squares DF Mean Square F-value P-value
Prob > F
Comment
Model 19968.291 7 2852.613 34.655 <0.001
Significant
A-Cross P 11397.041 1 11397.041 138.458 <0.0001
B-MW Drying
time
590.0416 1 590.041 7.168 0.0159
C-Humidity
Expo time
3105.375 1 3105.375 37.726 <0.0001
AB 63.375 1 63.375 0.769 0.3925
AC 2.041 1 2.041 0.024 0.8767
BC 4240.041 1 4240.041 51.510 <0.0001
ABC 570.375 1 570.375 6.929 0.0175
Pure Error 1399.333 17 82.313
Cor Total 24582.740 26
Std. Dev. 0.907
Mean 51.52
C.V % 17.61
R2 0.9345
36. 9/16/2016 36
OPTIMIZATION: HALF -NORMAN PLOT FOR DT
• Positive Effect : MWT so DT
• Negative Effect: Crosspovidone concentreation and RH DT.
• Significant effects were selected based on Half normal plot.
37. 9/16/2016 37
Predicted Vs actual values were closely related to each other
with a predicted R square value of 0.934
OPTIMIZATION STUDY –DIAGNOSTIC PLOTS
38. 9/16/2016 38
OPTIMIZATION STUDY –MODEL GRAPH FOR
DT
Response surface plots of the disintegration time as a function of concentration
of crospovidone (A) and humidity exposer time (C)
DT= +32.46 – 21.79*A + 4.96*B – 11.37*C + 1.62*A*B + 0.29*AC –
13.29*B*C + 4.88 A*B*C
42. 9/16/2016 42
Optimized formula
Based on the factorial design batches and their response graphs, the highly porous ODT,
formulation was optimized, which gives us very low DT and optimum hardness
Ingredients (mg/tablet) Concentration
Complex (equivalent to 25mgLMG ) 135.82
DC Mannitol 47.36
Crospovidone 10.8
PVP k-25 2
Flavor 2
Sod. Starch Fumarate 2
Tablet wt.(mg) 200
Hardness(Kg/Cm) Initial 2
After MWT* 2.8
30 min Humidity then
MWT*
5.5
DT (Second) Initial 135
After MWT* 120
30 min Humidity then
MWT*
22
44. 9/16/2016 44
IN-VITRO EVALUATION AND
CHARACTERIZATION
a) Pre Compression Parameters
Batch
No.
Bulk Density
(g/cm3)
Tapped Density
(g/cm3)
Angle of
Repose (ϴ)
Carr’s
Index (%)
Hausner’s Ratio
40 0.53±0.006 0.58±0.005 29.18±0.30 8.62 1.09
b) Tablet Parameters
Batch
No.
Thickness
(mm)
Diameter
(mm)
Weight
variation
(mg)
Drug
Content
(%)
Friability
(%)
Wetting
Time
(Sec)
DT
(Sec)
Hardness
(kg/cm)
40 2.24 ± 0.07 2.28 ± 0.08 201± 04 99.13 0.25 16 22 5.2
(n=3)
(n=3)
Tablet Wetting time images at various stages
45. 9/16/2016 45
c) In-vitro Drug Release
Continue….
-20
0
20
40
60
80
100
120
0 5 10 15 20 25 30 35
%Cumuletiverelease
Time (Min)
Batch no 40
Drug
According to these results, the optimized formulation with B-
CD inclusion complex released nearly 100% of the drug
within 5 min, whereas pure LMG exhibited a release of 50 %
after 30 min.
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d) SEM Analysis
Scanning electron microscope images of tablet internal surface
of tablet (a) microwave untreated and (b) microwave treated
(a) (b)
48. 9/16/2016 48
Aim: Design of taste masked ODT of LMG a bitter drug using electronic tongue.
TASTE MASKING AND EVALUATION USING
ELECTRONIC TONGUE
PROCESSES FOR TASTE MASKING
TASTE
MASKING
By sweeteners
and flavoring
agents
Reducing the
sensitivity of
taste buds
Inhibition of
the drugs
dissolution in
the mouth
Microencapsul
ation
By
Complexation
49. 9/16/2016 49
Electronic Tongue
Electronic tongue (ET) is “a multisensor system, which consists of a number of low-
selective sensors and uses advanced mathematical procedures for signal processing
based on pattern recognition and/or multivariate data analysis artificial neural
networks (ANNs) and principal component analysis (PCA), etc”.
By using ET we can do quantitative and qualitative analysis
ET is based on a partially selective sensor that operates on the dissolved samples
Up to date four best known electronic tongues have been developed by
1. Toko in Japan (Toko et al. 1997)
2. The Swedish Sensor Centre S-SENCE (Winquist et al. 1997, 2000)
3. The University of Saint-Petersburg in Russia (Legin et al. 1999, Beullens et al. 2006)
4. Alpha M.O.S. in France (Alpha M.O.S. 2001)
50. 9/16/2016 50
Principle
The electronic tongue works on the basis of potentiometric technique and having multiple
electrodes. This technique determines the concentration of ions in solutions in terms of current flow
as a function of voltage when the polarization of ions occurs around the electrode. This measured
voltage is a function of different chemical composition and hence can be used for the identification
of different taste, as different taste is related to different chemical composition.
Instrumentation of electronic tongue developed by university of Saint-Petersburg
19 cross sensitive potentiometric sensors for the analysis of taste masking formulations. The
potentiometric sensors are distributed as follows
1. 9 PVC plasticized type Anionic sensors
2. 6 PVC plasticized Catanionic sensors
3. 2 Chalcogenide Glass type with pronounced red/ox sensitivity
4. 1 crystalline type
5. Standard glass pH sensor
6. Ag/ AgCl reference electrodes
7. 32-channel digital mV-meter connected to a PC through USB interface. Precision in potential
measurements was 0.1 mV.
Data Processing
Data processing done by using principle component analysis (PCA)
PCA is a projection method that allows one to efficiently reduce the number of original variables
and reject noise
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Method
All the samples were delivered in the solid form as tablets or powders. Aqueous solution dispersion
of the samples was prepared for measurement by the electronic tongue. Distilled water (100ml)
from a single source was used throughout the experiment as sample diluent and for washing the
sensors. Measurement time was 3 minutes for each sample. Before & after the measurements,
sensor array was washed several times with distilled water to bring the potentials of the sensors to
initial reading
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Evaluation OF TASTE MASKING
a) Lamotrigne (API) and Placebo Interpretation by Principle Component
Analysis
Discrimination of formulation with API and Placebo by (PCA)
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b) 3D Plot for API, Taste Masked Formulations and Related Placebo
Formulations
3D plot for API and taste masked formulation
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c) Projection of Lamotrigine and Taste Masked Formulations
Pattern recognition of taste masked formulation against lamotrigine by PCA
Conclusion
An electronic tongue was successfully used to develop taste masked lamotrigine
ODTs.
58. 9/16/2016 58
In-Vitro Drug Release of Stability Batch
0
20
40
60
80
100
120
0 5 10 15 20
%Cumulativerelease
Time (min)
Drug release for stability batch
1 month 30 0C/ 65 RH
2 month 30 0C/ 65 RH
1 month 40 0C/ 75 RH
2 month 40 0C/ 75 RH
No significant changes were observed in batch no. 40 appearance, weight,
assay and in-vitro release profile of developed Final ODTs formulation
suggested by using factorial design after three months of accelerated stability
study suggesting good stability.
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HIGHLIGHTS
Porous ODTs have been successfully developed by using microwave technology, which
is a green approach for development of ODTs.
Lamotrigine used as a model drug for development of ODTs by microwave technology.
At the time of development of a tablet, water is a crucial parameter for developing pores
in tablets.
Lamotrigine being partially water soluble is made to complex with beta-cyclodextrin to
enhance its water solubility as well as bioavailability with additional advantage of
masking its bitter taste.
Complexation was confirmed by phase solubility study and molecular docking study.
The taste masked formulation was prepared for patient compliance and successful In-
vitro analysis done by using electronic tongue.
The developed formulation is easy, simple and the method is scalable.
CQA, CQM and CPP are successfully optimized by 23 factorial analysis, which resulted
in rapid disintegration and acceptable hardness with approximately 99% drug release
within 5 min for optimized formulation.
ODTs formulations developed by microwave technology were studied for its stability
and results demonstrated 2 months stability.
Developed technology provides an alternative to conventional technologies as well as
some patented technologies.
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CONCLUSION
Microwave assisted approach for the development of
ODTs is successful.
Being a simple, ease of scale-up is yet another major
advantage of Microwave technology.
Moreover Electronic Tongue is promising alternative
to human panel for tasting bitter formulations and
optimization.
61. 9/16/2016 61
ACKNOWLEDGEMENTS
My mentor Prof. Padma V. Devarajan
TEQIP granting me fellowship
Director, Prof. G.D. Yadav
All faculty and staff members
RPG Life Science (Mumbai India) for providing me gift sample of
Lamotrigine
Prof. Laddha. ICT, Mumbai
Prof. Degani ICT, Mumbai
Mr. Maltesh Joshi
PVD lab mates
KGA, PRV, VNT, VBP lab mates, my friends and all my classmates
My Family
ICT Hostel
GOD ALMITY
Apology for any omission
At 2.5% concentration of crosspovidone in DC15 and DC18 we are getting acceptable limit of DT 57 and 48 Second's respectively.
With crosspovidone in presence of MW drying we are getting good hardness witch is in acceptable limit.
There is no core observed with crosspovidone.
Pregeletinized starch (batch no DC15) showing no additional advantage in decreasing DT time as well as increasing hardness compared to formulation containing only lactose (batch no DC18).
Batches with the drug βCD revealed small black spot in the center of tablet and high swelling when subjected to MWT for 5min at 490 Watt. However spots were not seen when MWT time was reduced from 5min to 3.5min. Drug loaded tablets prepared using βCD DC20 showed lower DT of less than 60 seconds while DC21 with HPβCD exhibited very high DT. Hence, to bring down the DT further, batches DC22 and DC23 were prepared with increased concentration of crospovidone of which DC22 batch revealed very low DT, while DC23 comprising HPβCD showed very high DT greater than 5 minutes with increased hardness when subjected to MWT (Ref table no. 6.6). Hence batch DC22 comprising LMG-βCD complex which gave us very low DT (23 sec.) and good hardness (5.5) using MWT would be considered for application of factorial analysis, to arrive at an optimum formulation.
Concentration of superdisintegrant (crospovidone), humidity exposer time and microwave heating were the three independent variables (or factors) chosen at three levels.
The Model F-value of 1301.58 implies the model is significant. There is only a 0.01% chance that a "Model F-Value" this large could occur due to noise. Values of "Prob > F" less than 0.0500 indicate model terms are significant.
The half-normal plot is used to select effects to be included in the model. Large effects (absolute values) appear in the upper-right section of the plot. The lower-left portion of the plot contains effects caused by noise rather than a true effect.
The dissolution rate of LMG-B-CD complex shows an increase as compared to that of LMG alone. The faster dissolution rate obtained with an inclusion complex can be attributed to the decrease in crystallinity of LMG as confirmed by XRD analysis. Improvement in LMG wettability and formation of readily soluble complexes in the dissolution medium are possible reasons cited in the literature
Plasticized PVC based sensors are used because they show the same type of sensing activity with different active substances and it can be used in sensors with different working principle (Legin et al. 2003). Use of Ion-selective Electrodes (ISEs) allows us to determine the concentration of a specific ion in aqueous and in rare cases, non-aqueous solutions (ISEs like anionic and cationic). On the basis of cross-sensitivity studies in most cases even very non-selective or cross-sensitive sensors would not respond to any ion or substance in solution. Cross-sensitivity parameters based on the sensitivity study of chalcogenide glass electrodes to a set of heavy metals. So that the sensitivity of the sensors with chalcogenide glass membrane to heavy metal cations (e.g. copper, lead, cadmium, zinc, iron and uranium at different oxidation states, etc.) were investigated and used as a sensory electrode (Legin et al. 1999).
Ag/AgCl reference electrodes sensors displayed sensitivity to inorganic and organic taste substances such as: NaCl, KCl and KBr (salty), HCl,
We are able to discriminate between formulations, API alone and placebo formulation. In Fig. 8.1 we can clearly see that right hand side was completely acquired by API alone and taste masked formulations and in left side all placebo formulations were well discriminated. Here we can observe that the distance between API and placebo formulation and the taste masked formulations were relatively large. Fig. 8.1 demonstrates that only API and formulation batch no 23, 24, 25, 27 are in one plane (means they are showing some common characteristics) and batch no 26, 28, 29 and 30 are in another plane (Means there is some difference in their characteristic compared to pure API). Similar trend can be seen in placebo formulation which can be clearly seen in 3D plot (Fig. 8.2)
we can cleary see all the taste masked fomulations and API are clearly discriminated and they lie on different planes. Some of taste masked formulations are overlapped like DC23, DC24 and DC25 and some formulations are in the plane of API. This type of discrimination might be due to different chemical composition and the nature of the formation of cationic and anionic condition in water medium. From the above data we can presume that the electronic tongue was capable of correctly classifying all the samples, even though the substances with the same taste modality might have had a different chemical nature.
API and formulations DC23, 24, 25, 27 seem to be in the same plane and some of them are overlapping with each other. This means they have similar ionic/non ionic activity (these formulations share common characteristics with pure lamotrigine) thus other ingredients are having less impact on taste masking of lamotrigine. But DC29, 28, 30 are dissimilar to the group containing pure API (lamotrigine). In that DC29 the farthest group lies on left side of projection graph. This may be due to the impact of taste maskig ingredients, and can be due to change in ionic/non ionic activity (Martyna et al. 2010). From these results we can conclude that formulation DC29 was showing the best taste masking effect than others.
