FORMULATION STUDIES ON A DISPERSIBLE ISONIAZID TABLET FOR PAEDIATRIC USE
1. FORMULATION STUDIES ON A DISPERSIBLE ISONIAZID TABLET FOR PAEDIATRIC USE
Anirban Nandi*(anirbanbcrcp@gmail), Subhabrata Ray and Subrata Chakraborty
Dr. B. C. Roy College of Pharmacy & Allied Health Sciences, Durgapur
INTRODUCTION
Paediatric patient face difficulties in swallowing conventional oral dosage
forms due to dysphasia. Tackling this problem led to the development of
novel type of solid oral dosage forms called dispersible tablets, which
disintegrate and dissolve rapidly in saliva without the need of drinking
water. In such cases, bioavailability of drug is significantly greater than
those observed from conventional tablet dosage form by avoiding first
pass metabolism.
Tuberculosis is an infectious disease caused by the Mycobacterium
tuberculosis. Although the primary infection site always involves the
lungs, other organ systems. Tuberculosis is usually chronic and may be
almost lifelong affected .
It has been estimated that there are worldwide 4,90,000 Paediatric cases
and 64,000 child death/year due to active Tuberculosis (WHO, 2012).
National Institute of Child Health and FDA Paediatric Advisory
Committee report that there is a severe lack of suitable child-friendly
formulations for many drugs that include Isoniazid (INH). Existing oral
immediate release, adult strength dosage forms available are generally not
designed for flexible/alternate use, they are difficult to adopt to dosing
based on age and or weight, which is customary in children. For pediatric
use, dispersible tablets (DTs) offer distinct advantages over other
approaches. This is also endorsed in the 2008 Children Medicine Guide of
UNICEF. This is particularly relevant for tuberculosis, where stability,
long shelf life, increased bioavailability, reduced cost of manufacturing,
transport and storage are all critical for accessible and affordable therapy.
Hence, the work aimed to develop DTs of Isoniazid by wet granulation.
DTs are converted into easy to swallow suspension on contact with saliva,
without the need of extra liquid intake.
The main objective of this study was to develop dispersible paediatric
tablets of Isoniazid by wet granulation. The formulations were prepared
by using a blend of superdisintregrants such as sodium starch glycolate
and Croscarmellose sodium. The study were to investigate the
performance of superdisintregrants and effect of other process variables
on the characteristic of the Isoniazid dispersible formulations and evaluate
the in vitro performance of the formulations.
MATERIALS & METHODOLOGY
Drug and chemicals:-
Isoniazid was a gift sample from lupin pharmaceutical, Gujarat.
Preformulation studies:-
Determination of melting point:-Melting point of isoniazid was
determined by capillary method.
Solubility study:-Solubility analysis of isoniazid was carried out
using different solvent like water, methanol, ethanol, acetone,
chloroform, ether, 0.1(N) HCl and phosphate buffer pH 6.8 / 7.4.
Physical compatible study:-Drug and excipients were taken in the
ratio of 1:1 and the vials were stored in the stability chamber at 40
ºC/75 % RH. These sample was checked for physical changes every
week for a month.
Determination of λ-max of both drugs:-Solution containing 10
µg/ml of isoniazid was prepared and scanned over wavelength range
of 400-200 nm. Wavelength of which highest absorbance was
observed and recorded.
Preparation of stock solution:-Standard stock solution (100 µg/ml)
of isoniazid was prepared in 0.1 (N) HCl.
Preparation of standard solutions of isoniazid:- From the above
prepared standard stock solution of isoniazid (100 µ/ ml) different
aliquots of various concentrations (1, 2.5, 5, 10, 25, 50, 75, 100 µ/ml)
were prepared using 0.1 (N) HCl. The absorbance was measured at λ-
max against the 0.1 (N) HCl as blank.
Preparation of Tablets:- First weight ingredient and also active
materials as per formula, all materials were passing through # 60
mesh, the powder mass was mixing properly. Then add the binding
solution (which make previously by distilled water). Mix properly
with binding solution and make it wet mass, the wet mass was
sieving through # 8 and granules was prepare, the granules were
drying in a tray drier at 600C for 20 min, after drying add the
lubricant and mix properly, then the granules were compressed by 10-
station rotary press (Rimek Minipress-1,Kalurka) .
Evaluation parameter of the formulation:-
Pre-compression parameters:-
Angle of Repose (θ):-Angle of repose is calculated using following
equation:-
θ = tan-1 h/r, Where, h = height of pile, r = radius of the pile.
Bulk density& tapped density:- Measured via cylinder tapping
method. The porcess of tapping is continued until no further change
in volume is noted. From the finding, Carr”s index (I) & Haussers
Ratio (H) were calculated.
Post Compression Parameters:-
Thickness & diameter:- Measured using vernier calipers
Hardness Test:- measured by using hardness tester (Pfizer hardness
tester).
Friability Test:- Measured using Roche Friabilator.
Weight Variation Test & Drug Content Uniformly:- As per I.P.
In-Vitro disintegration time:-
This in-vitro disintegration time of a tablet is determined using
disintegration test apparatus as per IP specifications. One tablet is
placed in each of the six tubes of the basket. Add a disc to each tube
and run the apparatus using 0.1(N) Hcl maintained at 37 ± 2° C as the
immersion liquid. The time in seconds taken for complete
disintegration of the tablet with no palpable mass remaining in the
apparatus is measured and recorded.
In-vitro dissolution studies:-
In-vitro release study is performed using tablet dissolution test
apparatus USP, apparatus (II).
Ingredients
(mg/tab)
F1 F2 F3 F4 F5
Isoniazid 60 60 60 60 60
Starch 80 40 90 60 70
Manitol 83 120 60 40 30
M C C 25 20 20 62 55
S S G 10 15 20 23 25
Croscarmellose
sodium.
3 5 8 12 15
PVP-K 30 3 5 7 8 8
Talc 2.5 2.5 2.5 2.5 2.5
Mag.stearate 3.5 2.5 2.5 2.5 4.5
Total weight (mg) 270 270 270 270 270
RESULTS & DISCUSSIONS
Preformulation Studies:-
Isoniazid melting range was found from 171˚C to 173˚C, which corresponds to
reported value.
Physical compatibility study:- No visible physical incompatibility could be
detected.
Determination of λ-max of drugs:- λ-max was detected 261.9 nm in 0.1 (N)
HCl medium.
Standard Curve for Isoniazid:-
The standard calibration of curves 261.9 nm show the slope 0.003 and
coefficient of determination (R2) of 0.966.
Pre-compression Parameters Table:-
Formulation
code
Angle of
repose (0)
Bulk density
(gm/cm3)
Tapped
density
(gm/cm3)
Hausner’s
Ratio
Carr’s index
F1 28.30±0.62 0.524±0.01 0.621±0.01 1.185 15.61
F2 30.89±0.74 0.527±0.00 0.620±0.01 1.176 15.00
F3 27.64±o.61 0.683±0.00 0.891±0.01 1.304 23.344
F4 27.24±0.31 0.645±0.00 0.867±0.00 1.344 25.02
F5 25.45±0.49 0.542±0.00 0.611±0.01 1.127 11.29
Formulation
code
Uniformity
of thickness
(mm)
Uniformity
of diameter
(mm)
Hardness
(kg/cm2)
% Friability Uniformity
of weight
(mg)
F1 0.42±0.01 12.39±0.01 1.5±0.24 0.21±0.02 269.85±1.04
F2 0.41±0.05 12.04±0.01 1.5±0.24 0.25±0.33 270.12±1.24
F3 0.40±0.078 12.00±0.01 2.00±0.11 0.18±0.56 270.05±0.78
F4 0.41±0.90 12.04±0.01 2.5±0.11 0.15±0.00 270.47±1.09
F5 0.41±0.00 12.04±0.07 3.00±0.20 0.14±0.96 270.11±0.65
Formulation codes In vitro disintegration time
(sec)
Content uniformity (%)
F1 182±0.1134 98.468±1.3882
F2 169±0.5647 99.144±0.1991
F3 122±0.2561 98.126±0.4464
F4 107±0.1123 98.021±0.2441
F5 83±0.1752 100.115±0.1267
Post-compression Parameters Table:-
Discussion On Compatibility Studies of F-5 Formulation:-
IR spectrum of pure drug, polymer and crushed tablets were studied. The
characteristic absorption peaks of Isoniazid were obtained.
The FTIR spectra of pure Isoniazid indicated the characteristic absorption
stretch for C=O stretch band at 1666.50cm -1 and broad band’s at 3302.13,
3500.00 and 2866.22cm-1 for bonded N-H, N-H2 and C-H, stretch were
obtained. The figure point region FTIR spectra showed a characteristic
sharp peak at 1666.50, 1492.99, 1600cm-1 for C=O, ring -C=C and C=N.
The FTIR spectra of polymers indicates the characteristic absorption for –
C=N,-C-H, =C-H,-OH stretch band at 2137.13, 2848.85, 3280.92,
3523.95 cm-1 were obtained.
The FTIR spectra of crushed tablets indicates the characteristic absorption
stretch for C=O 1666.5 cm-1, N-H 3302.13cm-1, N-H2 3527.80cm-1, C-
H 2873.9cm-1, C=N 1600.92cm-1, -C=C 1488.18cm-1,-C=N 2119.77cm-1,
-C-H 2848cm-1, -OH 3527.80cm-1.
In comparison with the pure Isoniazid, the absorption peak of the spectra
for Isoniazid in its formulation showed no shift and no disappearance of
characteristic peaks suggest that there is no interaction between isoniazid
and other additives. No degradation of Isoniazid molecule was observed
during its formulation development, hence the drug-excipients
combinations used in the formulation development were compatible
under given set of conditions.
In-vitro release studies of Isoniazid formulation revealed that 99% of drug
was release from the formulation (F5) within 45 minutes. Formulation F 5
showed faster drug release in comparison to the marketed formulation of
Isoniazid.
Based on pre- & post compression characteristics of the formulations, the
tablets of formula F-5 were found to satisfy requirements of a dispersible
paediatric tablet of Isoniazid.
Comparative Studies of Isoniazid Dispersible Tablet F-5 Formulation
vs. Marketed Product:-
0
20
40
60
80
100
120
0 10 20 30 40 50 60 70 80 90 100
%
C
D
R
TIME (min)
F 5
Marketed
product
CONCLUTION
Overall results indicates that formulation F 5 was better one and satisfies all
the criteria as dispersible paediatric tablet of INH. Isoniazid showing
enhanced dissolution, may lead to improved bioavailability, improved
effectiveness and hence better patient compliance.
FUTURE DEVELOPMENT
If commercialized, it may fill the absence of an INH DT in the market.
REFERENCES
Guidelines for registration at fixed-dose combination medicinal product
(2005).In thirty-ninth report at the WHO expert committee on specifications
for pharmaceutical preparation. Geneva World Health Organization WHO
Technical Report Series, no.929, Annex J.
Pharmaceutical development for multisource (generic) pharmaceutical
products (working document QAS/08.251/Rev.1).
World Health Organization, Global Tuberculosis Report, 2015
WHO/HTM/TB/2015.22. Geneva, Switzerland report, 2015.32, [Last
accessed - 27. 05. 2016].
http://biospace.com. [Last accessed - 27. 05. 2016].
http.//apps who.int/. [Last accessed - 28.09.2016].
http.//WHO.in. [Last accessed - 28.09.2016].
http.//ich.org [Last accessed - 28.09.2016].
http.//ema.europa.eu [Last accessed - 29.09.2016].
http.//msfaccess.org/ [Last accessed - 29.09.2016].
Schaat HS, Moll AP, Dheda K. Multi drug and excessively drug resistance
tuberculosis in Africa and South America: epidemiology, diagnosis and
management in adult and children. Clinic chest Med 2009; 30. 667-683.
Graham SM, Grzemska M.R.P. Gie. The background and rationate for a
new fixed-dose combination for first-line treatment at tuberculosis in
children. Int J Tuberc Lung Dis. 2015; 19. 245-250.
Gopinath C, Bindu VH, Nischal A M. A overview on bi layered tablet
technology. J Global Trends Pharma 2013; 4.1077-1085.
Ivanovska V, Rademaker C M, Van D L, Mantel Tecuwisse A K.Pediatric
drug formulation: a review of challenger and progress, paediatrics 2014;
134. 361-372.
Cheng R, Guo X, Burusid Burusid B, Cough R.A review at fast dissolving
tablets. Pharm Tech, 2000; 11. 52-58.
Yang S, Jeong SH, Kimura S, Park K. Orally fast disintegrating tablets;
developments, technologies, taste-masking and clinical studies. Crit Rev
Ther Drug Carrier 2004; 21.433-76.
Bhandari S, Mitta Palli R K, Ramesh G, Yassani M R. Orodispersible
tablets; an overview. Asian J Pharmaceutics. 2008; 8. 22-27.
Chein Y W . Noval drug delivery systems. Marcel de k ker inc. 2nd ed.
New York 1992 PP. 139-140.
Gerbins PP . Remington . The science and practice of pharmacy (PA.
Lippincott Williams & wilkins). 2nd ed, Philadelphia 2005 PP. 916-918.
Shukla V, Nanjawade BK , Manvi F V, Dispersible drug delivery for
FORMULATION TABLE
Chemical Compatibility / FTIR Studies :- Isoniazid, Polymer, Crushed
Tablets.
The dissolution medium consisted of 900 ml 0.1(N) HCl maintained at
(37 ± 0.5) ° C rotated at 50 rpm at 9 samples are withdrawn and replaced
with fresh medium. 9 ml sample are diluted to the aliquots are assayed
spectrophotometrically at λ-max.
![FORMULATION STUDIES ON A DISPERSIBLE ISONIAZID TABLET FOR PAEDIATRIC USE
Anirban Nandi*(anirbanbcrcp@gmail), Subhabrata Ray and Subrata Chakraborty
Dr. B. C. Roy College of Pharmacy & Allied Health Sciences, Durgapur
INTRODUCTION
Paediatric patient face difficulties in swallowing conventional oral dosage
forms due to dysphasia. Tackling this problem led to the development of
novel type of solid oral dosage forms called dispersible tablets, which
disintegrate and dissolve rapidly in saliva without the need of drinking
water. In such cases, bioavailability of drug is significantly greater than
those observed from conventional tablet dosage form by avoiding first
pass metabolism.
Tuberculosis is an infectious disease caused by the Mycobacterium
tuberculosis. Although the primary infection site always involves the
lungs, other organ systems. Tuberculosis is usually chronic and may be
almost lifelong affected .
It has been estimated that there are worldwide 4,90,000 Paediatric cases
and 64,000 child death/year due to active Tuberculosis (WHO, 2012).
National Institute of Child Health and FDA Paediatric Advisory
Committee report that there is a severe lack of suitable child-friendly
formulations for many drugs that include Isoniazid (INH). Existing oral
immediate release, adult strength dosage forms available are generally not
designed for flexible/alternate use, they are difficult to adopt to dosing
based on age and or weight, which is customary in children. For pediatric
use, dispersible tablets (DTs) offer distinct advantages over other
approaches. This is also endorsed in the 2008 Children Medicine Guide of
UNICEF. This is particularly relevant for tuberculosis, where stability,
long shelf life, increased bioavailability, reduced cost of manufacturing,
transport and storage are all critical for accessible and affordable therapy.
Hence, the work aimed to develop DTs of Isoniazid by wet granulation.
DTs are converted into easy to swallow suspension on contact with saliva,
without the need of extra liquid intake.
The main objective of this study was to develop dispersible paediatric
tablets of Isoniazid by wet granulation. The formulations were prepared
by using a blend of superdisintregrants such as sodium starch glycolate
and Croscarmellose sodium. The study were to investigate the
performance of superdisintregrants and effect of other process variables
on the characteristic of the Isoniazid dispersible formulations and evaluate
the in vitro performance of the formulations.
MATERIALS & METHODOLOGY
Drug and chemicals:-
Isoniazid was a gift sample from lupin pharmaceutical, Gujarat.
Preformulation studies:-
Determination of melting point:-Melting point of isoniazid was
determined by capillary method.
Solubility study:-Solubility analysis of isoniazid was carried out
using different solvent like water, methanol, ethanol, acetone,
chloroform, ether, 0.1(N) HCl and phosphate buffer pH 6.8 / 7.4.
Physical compatible study:-Drug and excipients were taken in the
ratio of 1:1 and the vials were stored in the stability chamber at 40
ºC/75 % RH. These sample was checked for physical changes every
week for a month.
Determination of λ-max of both drugs:-Solution containing 10
µg/ml of isoniazid was prepared and scanned over wavelength range
of 400-200 nm. Wavelength of which highest absorbance was
observed and recorded.
Preparation of stock solution:-Standard stock solution (100 µg/ml)
of isoniazid was prepared in 0.1 (N) HCl.
Preparation of standard solutions of isoniazid:- From the above
prepared standard stock solution of isoniazid (100 µ/ ml) different
aliquots of various concentrations (1, 2.5, 5, 10, 25, 50, 75, 100 µ/ml)
were prepared using 0.1 (N) HCl. The absorbance was measured at λ-
max against the 0.1 (N) HCl as blank.
Preparation of Tablets:- First weight ingredient and also active
materials as per formula, all materials were passing through # 60
mesh, the powder mass was mixing properly. Then add the binding
solution (which make previously by distilled water). Mix properly
with binding solution and make it wet mass, the wet mass was
sieving through # 8 and granules was prepare, the granules were
drying in a tray drier at 600C for 20 min, after drying add the
lubricant and mix properly, then the granules were compressed by 10-
station rotary press (Rimek Minipress-1,Kalurka) .
Evaluation parameter of the formulation:-
Pre-compression parameters:-
Angle of Repose (θ):-Angle of repose is calculated using following
equation:-
θ = tan-1 h/r, Where, h = height of pile, r = radius of the pile.
Bulk density& tapped density:- Measured via cylinder tapping
method. The porcess of tapping is continued until no further change
in volume is noted. From the finding, Carr”s index (I) & Haussers
Ratio (H) were calculated.
Post Compression Parameters:-
Thickness & diameter:- Measured using vernier calipers
Hardness Test:- measured by using hardness tester (Pfizer hardness
tester).
Friability Test:- Measured using Roche Friabilator.
Weight Variation Test & Drug Content Uniformly:- As per I.P.
In-Vitro disintegration time:-
This in-vitro disintegration time of a tablet is determined using
disintegration test apparatus as per IP specifications. One tablet is
placed in each of the six tubes of the basket. Add a disc to each tube
and run the apparatus using 0.1(N) Hcl maintained at 37 ± 2° C as the
immersion liquid. The time in seconds taken for complete
disintegration of the tablet with no palpable mass remaining in the
apparatus is measured and recorded.
In-vitro dissolution studies:-
In-vitro release study is performed using tablet dissolution test
apparatus USP, apparatus (II).
Ingredients
(mg/tab)
F1 F2 F3 F4 F5
Isoniazid 60 60 60 60 60
Starch 80 40 90 60 70
Manitol 83 120 60 40 30
M C C 25 20 20 62 55
S S G 10 15 20 23 25
Croscarmellose
sodium.
3 5 8 12 15
PVP-K 30 3 5 7 8 8
Talc 2.5 2.5 2.5 2.5 2.5
Mag.stearate 3.5 2.5 2.5 2.5 4.5
Total weight (mg) 270 270 270 270 270
RESULTS & DISCUSSIONS
Preformulation Studies:-
Isoniazid melting range was found from 171˚C to 173˚C, which corresponds to
reported value.
Physical compatibility study:- No visible physical incompatibility could be
detected.
Determination of λ-max of drugs:- λ-max was detected 261.9 nm in 0.1 (N)
HCl medium.
Standard Curve for Isoniazid:-
The standard calibration of curves 261.9 nm show the slope 0.003 and
coefficient of determination (R2) of 0.966.
Pre-compression Parameters Table:-
Formulation
code
Angle of
repose (0)
Bulk density
(gm/cm3)
Tapped
density
(gm/cm3)
Hausner’s
Ratio
Carr’s index
F1 28.30±0.62 0.524±0.01 0.621±0.01 1.185 15.61
F2 30.89±0.74 0.527±0.00 0.620±0.01 1.176 15.00
F3 27.64±o.61 0.683±0.00 0.891±0.01 1.304 23.344
F4 27.24±0.31 0.645±0.00 0.867±0.00 1.344 25.02
F5 25.45±0.49 0.542±0.00 0.611±0.01 1.127 11.29
Formulation
code
Uniformity
of thickness
(mm)
Uniformity
of diameter
(mm)
Hardness
(kg/cm2)
% Friability Uniformity
of weight
(mg)
F1 0.42±0.01 12.39±0.01 1.5±0.24 0.21±0.02 269.85±1.04
F2 0.41±0.05 12.04±0.01 1.5±0.24 0.25±0.33 270.12±1.24
F3 0.40±0.078 12.00±0.01 2.00±0.11 0.18±0.56 270.05±0.78
F4 0.41±0.90 12.04±0.01 2.5±0.11 0.15±0.00 270.47±1.09
F5 0.41±0.00 12.04±0.07 3.00±0.20 0.14±0.96 270.11±0.65
Formulation codes In vitro disintegration time
(sec)
Content uniformity (%)
F1 182±0.1134 98.468±1.3882
F2 169±0.5647 99.144±0.1991
F3 122±0.2561 98.126±0.4464
F4 107±0.1123 98.021±0.2441
F5 83±0.1752 100.115±0.1267
Post-compression Parameters Table:-
Discussion On Compatibility Studies of F-5 Formulation:-
IR spectrum of pure drug, polymer and crushed tablets were studied. The
characteristic absorption peaks of Isoniazid were obtained.
The FTIR spectra of pure Isoniazid indicated the characteristic absorption
stretch for C=O stretch band at 1666.50cm -1 and broad band’s at 3302.13,
3500.00 and 2866.22cm-1 for bonded N-H, N-H2 and C-H, stretch were
obtained. The figure point region FTIR spectra showed a characteristic
sharp peak at 1666.50, 1492.99, 1600cm-1 for C=O, ring -C=C and C=N.
The FTIR spectra of polymers indicates the characteristic absorption for –
C=N,-C-H, =C-H,-OH stretch band at 2137.13, 2848.85, 3280.92,
3523.95 cm-1 were obtained.
The FTIR spectra of crushed tablets indicates the characteristic absorption
stretch for C=O 1666.5 cm-1, N-H 3302.13cm-1, N-H2 3527.80cm-1, C-
H 2873.9cm-1, C=N 1600.92cm-1, -C=C 1488.18cm-1,-C=N 2119.77cm-1,
-C-H 2848cm-1, -OH 3527.80cm-1.
In comparison with the pure Isoniazid, the absorption peak of the spectra
for Isoniazid in its formulation showed no shift and no disappearance of
characteristic peaks suggest that there is no interaction between isoniazid
and other additives. No degradation of Isoniazid molecule was observed
during its formulation development, hence the drug-excipients
combinations used in the formulation development were compatible
under given set of conditions.
In-vitro release studies of Isoniazid formulation revealed that 99% of drug
was release from the formulation (F5) within 45 minutes. Formulation F 5
showed faster drug release in comparison to the marketed formulation of
Isoniazid.
Based on pre- & post compression characteristics of the formulations, the
tablets of formula F-5 were found to satisfy requirements of a dispersible
paediatric tablet of Isoniazid.
Comparative Studies of Isoniazid Dispersible Tablet F-5 Formulation
vs. Marketed Product:-
0
20
40
60
80
100
120
0 10 20 30 40 50 60 70 80 90 100
%
C
D
R
TIME (min)
F 5
Marketed
product
CONCLUTION
Overall results indicates that formulation F 5 was better one and satisfies all
the criteria as dispersible paediatric tablet of INH. Isoniazid showing
enhanced dissolution, may lead to improved bioavailability, improved
effectiveness and hence better patient compliance.
FUTURE DEVELOPMENT
If commercialized, it may fill the absence of an INH DT in the market.
REFERENCES
Guidelines for registration at fixed-dose combination medicinal product
(2005).In thirty-ninth report at the WHO expert committee on specifications
for pharmaceutical preparation. Geneva World Health Organization WHO
Technical Report Series, no.929, Annex J.
Pharmaceutical development for multisource (generic) pharmaceutical
products (working document QAS/08.251/Rev.1).
World Health Organization, Global Tuberculosis Report, 2015
WHO/HTM/TB/2015.22. Geneva, Switzerland report, 2015.32, [Last
accessed - 27. 05. 2016].
http://biospace.com. [Last accessed - 27. 05. 2016].
http.//apps who.int/. [Last accessed - 28.09.2016].
http.//WHO.in. [Last accessed - 28.09.2016].
http.//ich.org [Last accessed - 28.09.2016].
http.//ema.europa.eu [Last accessed - 29.09.2016].
http.//msfaccess.org/ [Last accessed - 29.09.2016].
Schaat HS, Moll AP, Dheda K. Multi drug and excessively drug resistance
tuberculosis in Africa and South America: epidemiology, diagnosis and
management in adult and children. Clinic chest Med 2009; 30. 667-683.
Graham SM, Grzemska M.R.P. Gie. The background and rationate for a
new fixed-dose combination for first-line treatment at tuberculosis in
children. Int J Tuberc Lung Dis. 2015; 19. 245-250.
Gopinath C, Bindu VH, Nischal A M. A overview on bi layered tablet
technology. J Global Trends Pharma 2013; 4.1077-1085.
Ivanovska V, Rademaker C M, Van D L, Mantel Tecuwisse A K.Pediatric
drug formulation: a review of challenger and progress, paediatrics 2014;
134. 361-372.
Cheng R, Guo X, Burusid Burusid B, Cough R.A review at fast dissolving
tablets. Pharm Tech, 2000; 11. 52-58.
Yang S, Jeong SH, Kimura S, Park K. Orally fast disintegrating tablets;
developments, technologies, taste-masking and clinical studies. Crit Rev
Ther Drug Carrier 2004; 21.433-76.
Bhandari S, Mitta Palli R K, Ramesh G, Yassani M R. Orodispersible
tablets; an overview. Asian J Pharmaceutics. 2008; 8. 22-27.
Chein Y W . Noval drug delivery systems. Marcel de k ker inc. 2nd ed.
New York 1992 PP. 139-140.
Gerbins PP . Remington . The science and practice of pharmacy (PA.
Lippincott Williams & wilkins). 2nd ed, Philadelphia 2005 PP. 916-918.
Shukla V, Nanjawade BK , Manvi F V, Dispersible drug delivery for
FORMULATION TABLE
Chemical Compatibility / FTIR Studies :- Isoniazid, Polymer, Crushed
Tablets.
The dissolution medium consisted of 900 ml 0.1(N) HCl maintained at
(37 ± 0.5) ° C rotated at 50 rpm at 9 samples are withdrawn and replaced
with fresh medium. 9 ml sample are diluted to the aliquots are assayed
spectrophotometrically at λ-max.](https://image.slidesharecdn.com/posterpresentationforgcts-171123052031/85/FORMULATION-STUDIES-ON-A-DISPERSIBLE-ISONIAZID-TABLET-FOR-PAEDIATRIC-USE-1-320.jpg)
