Last updated: May 26, 2019
Topic: BusinessEnergy
Sample donated:

Distilled H2O used was obtained from an all glass electrically heated still and maintain stored in a 5 litres good leached and stopper bottle, pH 5.8A±as determined by corning pH metre and surface tenseness 72A± 0.2m Nm-1 at 20oC.

Clash and daze are the forces that induce tablets to bit, cap or interruption. As a consequence equipment such as Curio Friabilator was developed. The unit causes self scratch of the tablets as the cylinder subdivision rotates. The tablets besides undergo daze as they fall 6 inches on each bend. After 4 proceedingss of this procedure or 100 revolutions, the tablets are weighed and compared to their original weight.

The value is expressed as per centum w/w.Acceptable bounds of weight loss are less than 1 per centum. By and large, when cresting occurs or tablets break during the trial, crumbliness values are non valid and are non calculated. When tablets lose wet on aging, they may go more crumbly. ( Javaid, 1993 )

The setup was manufactured by Curio, theoretical account FB-098.It was supplied by Technologies link, Islamabad Pakistan.

3-Disintegration Test Apparatus:

The setup was manufactured by Curio, theoretical account DS-0702.It was supplied by Technologies link, Islamabad Pakistan. It was manufactured under specification

4-Double Beam UV Spectrophotometer ( Hitachi, U-2001 Spectrophotometer, Japan )

Determination of spectrophotometer measurings are based on the soaking up of beaming energy by organic molecules at a particulate wavelength in the UV ( UV,180-380nm ) or seeable part ( 380-800nm ) .The soaking up of visible radiation at specific wavelengths due to electronic excitement is by and large characteristic of the chemical nature of the absorbing species and can be used for the finding of substances.

Harmonizing to Beer Lambert ‘s jurisprudence, the optical density at a specific wavelength is straight relative to the concentration of solute and way length of the sample.

Mathematically, it is expressed as,

A=acl

Where:

A=Absorbance,

a= Absorptivity,

c=Concentration and

l=Thickness of the cell or way length ( Javaid, 1993 )

3.3-METHODS:

1. Length and Thickness:

The length and thickness of tablets was measured with micron ( Vernier ) callipers. Mean of six tablets were taken for accurate consequence.

2. Hardness:

The hardness of tablets were determined by puting a tablet between right and left speculators and so get down look intoing hardness by turning on hardness examiner, until the tablet fractured and noted the reading. The same procedure with 4 tablets and the mean force in kilogram was calculated. Mean of six tablets were taken for accurate reading.

The apparatus consist of control panel, the item is given below:

Controls:

1. Get down

It is used to get down the Apparatus.

2. Stop

It is used to halt the Apparatus.

3. Print

It is used to publish the consequences.

4. Manner

It is used to alter the units i.e. ( kg & A ; Ibs ) .

Operation

Power on the setup by the Button on the Back side of the setup.

The Screen will demo the zeroing place so ready for trial thickness.

Then press start push Button.

Open the pan and topographic point the tablet in the borders between two skiding bars.

The setup will automatically give the thickness and so switch to hardness. Result will be in kilogram.

Record the reading and repetition on at least two more tablets.

After operation clean the setup and shut the pan.

The setup was supplied by Technologies Link, Islamabad Pakistan.

3. Weight Variation trial:

20 tablets were indiscriminately taken so the person and entire weight were determined by analytical balance and mean weight was calculated.The consequence of tablets was compared with B.P specification.

4. Decomposition Trial:

The U.S.P decomposition process was used in which six tablets from each trade name was kept in basket assembly suspended in a beaker incorporating distilled H2O keeping at 37A±0.5A°C with up and down frequence of 27 to 33 rhythms per minute, the clip required for complete decomposition of six tablets with in U.S.P specification.

Operation:

It is established to supply guidelines for the usage DISINTEGRATION TEST APPARATUS

ON the instrument form the button nowadays at the right sidelong side of the instrument.

Press the “ Power ” button and so “ HEAT ( 1 ) ” & amp ; “ STIRR ( 2 ) ” buttons present on the front panel.

Heating is start till the temperature of the liquid is 360 to 380C. The warming procedure is indicated by winking of ruddy visible radiation under “ HEAT ( 1 ) ” button. When the temperature reaches 370C, the ruddy visible radiation Michigans winking and the green visible radiation begins to wink.

For clip scene there are two manners i.e. “ Stopwatch ” and “ Lab counter ” .

Press “ M ” button to toggle between “ Stopwatch ” & amp ; “ Lab counter ” manner. The “ M ” button has two i.e. a-? ( above ) and a-„ ( below ) bespeaking towards lab counter and stop watch manner severally. The lamination of “ a-„ ” or “ a-? ” with ruddy visible radiation indicates that the several manner is activated.

When utilizing “ Stopwatch ” manner, merely press the “ ST/STOP ( 3 ) ” button followed by pressing “ OSCI ( 8 ) ” , the instrument starts operation.

To halt the stop watch, imperativeness “ ST/STOP ( 3 ) ” . Press “ RESET ( 4 ) ” to acquire zero clip on the show.

When utilizing the lab counter manner, imperativeness Shift button, “ 00.00 ” is displayed on the screen. The two nothings at the right side to the point shows clip in seconds and those at the left side shows clip in proceedingss. Press Shift button repeatedly to switch to the desired place. The activated nothing figure starts eye blink.

Press set button to put the specified clip.

Press “ ON/OFF ( 7 ) ” button, the clip starts in the countdown mode. When the clip reaches zero, the instrument bleeps.

5. Friability Test:

For crumbliness trial, 10 tablets were indiscriminately taken, so the person and entire weights were determined by analytical balance and mean weight was calculated. The tablets besides undergo daze and scratch as they fall 6 inches on each bend. After 100 revolutions, the tablets were weight and compared to their original weight. The loss due to scratch or clash or daze is the step of tablet crumbliness.

Operation:

It is established to supply guidelines for the usage of FRIABILITY TEST APPARATUS.

Accurately weigh required figure of tablets and topographic point in the membranophone. Fix the membranophone on the Friabilator.

Press “ 2 ( displacement ) ” button, “ 00.00 ” is displayed on the LCD. The two nothings at the right side of the point show seconds while those at the left side are for proceedingss. Press the displacement button repeatedly to switch to the desired place. The activated nothing figure starts eye blink.

Press “ 1 ( set ) ” button to put the coveted clip.

Press “ 3 ( start/stop ) ” button, the clip starts in a countdown mode.

When the clip is over the setup starts bleep.

6.Double beam UV Spectrophotometer:

The term used to denominate instrument which have a beaming energy-dispersing device, such as a beaming power is called Spectrophotometer.

In Double beam spectrophotometer a beginning of UV ( heavy hydrogen ) or seeable ( tungsten ) energy is required to breathe intense and unvarying radiations. A monochromator is used to insulate the coveted wavelength which enters the sample compartment through a narrow slit and base on ballss through the sample contained in a vitreous silica or glass cell. Appropriate exposure cell give information about the comparative soaking up by bring forthing an electrical signal proportional to the transmitted visible radiation. Upon elaboration of this signal the optical density along with wavelength of the sample or its spectrum may be recorded.

Operation:

It is established to supply guidelines for the usage of UV-VISIBLE SPECTROPHOTOMETER.

Get down the computing machine.

Switch on the UV-Visible spectrophotometer. A starting procedure Begins.

When the followers is displayed on the screen ;

( 1 ) Set method. ( 2 ) Run Method. ( 3 ) Set Curve. ( 4 ) List Methods

Press “ ESC ” button and so “ YES/REPEAT ” button. Now the screen shows the followers ;

( 1 ) Print Parameters. ( 2 ) Serial Control. ( 3 ) Mechanical Test. ( 4 ) Low Power.

Press “ 2 ” button, “ Consecutive Control ( Y/N ) ? ” is shown on the screen.

Press “ YES/REPEAT ” button. Now the spectrophotometer is connected to computing machine.

Double chink on the “ SF 1700 ” icon on the desktop of computing machine. A “ Metro lab ” duologue box appears.

“ Spectrum ” Manner:

Click on “ Lamp ” and so snap on “ Spectra ” ; the “ Spectra ” duologue box appears.

Travel to “ register ” bill of fare and snap “ new spectra ” ; the “ New Spectra ” duologue box appears.

Enter the coveted wavelength scope and chink “ All right ” .

“ Insert Cuvette ” box appears. Insert the cuvette, filled with space in to the cuvette holder and chink “ All right ” .

The clean scanning procedure starts. When the space is scanned, an “ Input a Name ” box appears.

Enter the name of solution and chink “ All right ” . The solution scanning procedure starts.

When the scanning is completed, the spectrum is appeared on the screen. Find out the wavelength of maximal optical density.

To salvage the spectrum, travel to register bill of fare and chink on “ save ” . Salvage the spectrum in the coveted finish.

In similar manner scan both sample and standard solutions.

“ PHOTOMETRIC Reading ” Manners:

Click on “ Lamp ” .

Click on “ Photometric Reading ” ; the “ Photometric Reading ” duologue box appears.

Enter the coveted wavelength in “ wavelength ” .

Insert cuvette, filled with space, in to the cuvette holder and chink “ Read Blank ” .

Remove the cuvette from the holder and rinse several times with test solution. Now insert the cuvette filled with trial solution into the cuvette holder and chink “ Read Sample ” .

Note the optical density of trial solution under “ Absorbance ” .

Measure the optical density of both standard and sample solutions in similar manner and infer the consequence by comparing.

Determination of pH:

pH is defined as, For practical intents, its definition is adequate for experiment.

pH should non be checked in greasy stage readying.

8. Clarity:

A liquid is considered clear if its lucidity is the same as that of H2O R or of the dissolver used when examined under the conditions given supra, or if its iridescence is non more marked than that of mention suspension I.

Particulate Contamination: Visible Atoms:

Apparatus:

The setup consists of following process:

_a matt-glass white panel of appropriate size held in a perpendicular place,

_a non-glass white panel of appropriate size held in a perpendicular place next to the black panel,

_an adjustable lamp holder fitted with a appropriate, shaded, white-light beginning and with a suited visible radiation diffusor ( a screening illuminator incorporating two 13 W fluorescent tubings, each 525mm in length, is suited ) .The strength of illuminatination at the sing point is maintained between 2000 lx and 3750 lx, nevertheless higher values are preferred for colored glass and plastic containers.

Method:

Remove any supportive labels from the container and wash and dry the exterior. Gently swirl or invert the container, confirm that air bubbles are non introduced, and observe for about 5 seconds in forepart of the black panel. At last, record the presence of any atoms.

13. Climatic Chamber

Operation:

It is established for Climatic Chamber

Connect the unit power cord to a land 3-prong.

Ensure the right collection by traveling the wheel manually to look into free motion of all burden parts and so exchange ON.

In instance of any unnatural sound from machine during its operation halt the machine and study to maintenance section.

14- Drug Assay Procedure for Tablets and Injections:

Drug checks:

The check for the active ingredient ( s ) in the preparations will be performed utilizing U.V spectroscopic method ( freshly developed or non-pharmacopoeia method ) . The checks will be repeated three times and the consequences will be presented as the mean of 3 findings ( A± criterion divergence ) at lambda ( EZ ) max 265nm.

Testing process for injections:

Preparation of standard solution: Take 100mg of VitaminD3 in 50ml of volumetric flask. Add 10ml formic acid in same volumetric flask and sonicate it for some clip. Add methyl alcohol to do up the volume up to the grade ( 50ml ) .

Then, take 2ml from the stock solution into 100ml volumetric flask.Then, add 1ml of 2,4 dinitrophenylhydrazin compound in 100ml volumetric flask and do up the volume up to the grade up of the flask.Then, take optical density at lambda soap 265nm.

Blank=Methanol.

Preparation of sample: Take 100mg equivalent of VitaminD3 in 50ml of volumetric flask. Add 10ml formic acid in same volumetric flask and sonicate it for some clip. Add methyl alcohol to do up the volume up to the grade ( 50ml ) .

Then, take 2ml of filtrate solution, through filtration ( 0.45 micron filter ) procedure, into 100ml volumetric flask.Then, add 1ml of 2,4 dinitrophenylhydrazin compound in 100ml volumetric flask and do up the volume up to the grade up of the flask.Then, take optical density at lambda soap 265nm.

Blank=Methanol.

U.V spectroscopic method is used to find the drug check by utilizing following expression

% Assay = Absorbance of sample x 100

Optical density of criterion

Testing process for Tablets:

Preparation of standard solution: Take 100mg of VitaminD3 in 50ml of volumetric flask. Add 10ml formic acid in same volumetric flask and sonicate it for some clip. Add methyl alcohol to do up the volume up to the grade ( 50ml ) .

Then, take 2ml from the stock solution into 100ml volumetric flask.Then, add 1ml of 2,4 dinitrophenylhydrazin compound in 100ml volumetric flask and do up the volume up to the grade up of the flask.Then, take optical density at lambda soap 265nm.

Blank=Methanol.

Preparation of sample: Take 100mg equivalent of VitaminD3 in 50ml of volumetric flask. Add 10ml formic acid in same volumetric flask and sonicate it for some clip. Add methyl alcohol to do up the volume up to the grade ( 50ml ) .

Then, take 2ml of filtrate solution, through filtration ( 0.45 micron filter ) procedure, into 100ml volumetric flask.Then, add 1ml of 2,4 dinitrophenylhydrazin compound in 100ml volumetric flask and do up the volume up to the grade up of the flask.Then, take optical density at lambda soap 265nm.

Blank=Methanol.

U.V spectroscopic method is used to find the drug check by utilizing following expression

% Assay = Absorbance of sample x 100

Optical density of criterion

Chapter NO 4

ACCELERATED STABILITY STUDY DATA

ACCELERATED STABILITY DATA OF VITAMIN D3 ( CHOLECALCIFEROL ) Tablet:

Stability tests & A ; Acceptance standards:

The trial parametric quantities mentioned in the stableness specification given below will be monitored during stableness survey of the drug substance. The batches of the merchandise kept on stableness at different storage conditions, should follow with these specifications. In instance of any deviant informations or an OOS state of affairs, a thorough probe shall be performed and based on the findings a determination will be made with respects to farther testing or temperament of the batch.

A-Stability Specification

( Qalsan D Tablets )

Note: The demand for decomposition does non use to Chewable Calcium Carbonate Tablets ( B.P, 2008, Volume 3 ) .

STABILITY DATA

( ACCELERATED STUDY )

Figure 6: Graph high spots relationship between Absorbance and Wavelength ( nm ) of Qalsan D in three different intervals ( Batch 001, 002 and 003 ) .

( a ) At 0 month ( Batch No:001 ) .

( B ) At 3 month ( Batch No:001 ) .

( degree Celsius ) At 6 month ( Batch No:001 ) .

( vitamin D ) At 0 month ( Batch No:002 ) .

( vitamin E ) At 3 month ( Batch No:002 ) .

( degree Fahrenheit ) At 6 month ( Batch No:002 ) .

( g ) At 0 month ( Batch No:003 ) .

( H ) At 3 month ( Batch No:003 ) .

( I ) At 6 month ( Batch No:003 ) .

B-Stability Specification

( Calgo Tablets )

Note: The demand for decomposition does non use to Chewable Calcium Carbonate Tablets ( B.P, 2008, Volume 3 ) .

STABILITY DATA

( ACCELERATED STUDY )

Figure 7: Graph high spots relationship between Absorbance and Wavelength ( nm ) of Calgo Tablets in three different intervals ( Batch 001, 002 and 003 ) .

( a ) At 0 month ( Batch No:001 ) .

( B ) At 3 month ( Batch No:001 ) .

( degree Celsius ) At 6 month ( Batch No:001 ) .

( vitamin D ) At 0 month ( Batch No:002 ) .

( vitamin E ) At 3 month ( Batch No:002 ) .

( degree Fahrenheit ) At 6 month ( Batch No:002 ) .

( g ) At 0 month ( Batch No:003 ) .

( H ) At 3 month ( Batch No:003 ) .

( I ) At 6 month ( Batch No:003 ) .

C-Stability Specification

( Osam-D Tablets )

STABILITY DATA

( ACCELERATED STUDY )

Figure 8: Graph high spots relationship between Absorbance and Wavelength ( nm ) of Osam-D in three different intervals ( Batch 001, 002 and 003 ) .

( a ) At 0 month ( Batch No:001 ) .

( B ) At 3 month ( Batch No:001 ) .

( degree Celsius ) At 6 month ( Batch No:001 ) .

( vitamin D ) At 0 month ( Batch No:002 ) .

( vitamin E ) At 3 month ( Batch No:002 ) .

( degree Fahrenheit ) At 6 month ( Batch No:002 ) .

( g ) At 0 month ( Batch No:003 ) .

( H ) At 3 month ( Batch No:003 ) .

( I ) At 6 month ( Batch No:003 ) .

ACCELERATED STABILITY DATA OF VITAMIN D3 ( CHOLECALCIFEROL ) Injection:

Stability tests & A ; Acceptance standards:

The trial parametric quantities mentioned in the stableness specification given below will be monitored during stableness survey of the drug substance. The batches of the merchandise kept on stableness at different storage conditions, should follow with these specifications. In instance of any deviant informations or an OOS state of affairs, a thorough probe shall be performed and based on the findings a determination will be made with respects to farther testing or temperament of the batch.

A-Stability Specification

( Indrop D Injection )

Figure 9: Graph high spots relationship between Absorbance and Wavelength ( nm ) of Indrop D Injection in three different intervals ( Batch 001, 002 and 003 ) .

( a ) At 0 month ( Batch No:001 ) .

( B ) At 3 month ( Batch No:001 ) .

( degree Celsius ) At 6 month ( Batch No:001 ) .

( vitamin D ) At 0 month ( Batch No:002 ) .

( vitamin E ) At 3 month ( Batch No:002 ) .

( degree Fahrenheit ) At 6 month ( Batch No:002 ) .

( g ) At 0 month ( Batch No:003 ) .

( H ) At 3 month ( Batch No:003 ) .

( I ) At 6 month ( Batch No:003 ) .

B-Stability Specification

( ED-3 Injection )

Figure 10: Graph high spots relationship between Absorbance and Wavelength ( nm ) of ED-3 Injection in three different intervals ( Batch 001, 002 and 003 ) .

( a ) At 0 month ( Batch No:001 ) .

( B ) At 3 month ( Batch No:001 ) .

( degree Celsius ) At 6 month ( Batch No:001 ) .

( vitamin D ) At 0 month ( Batch No:002 ) .

( vitamin E ) At 3 month ( Batch No:002 ) .

( degree Fahrenheit ) At 6 month ( Batch No:002 ) .

( g ) At 0 month ( Batch No:003 ) .

( H ) At 3 month ( Batch No:003 ) .

( I ) At 6 month ( Batch No:003 ) .

C-Stability Specification

( Cara-In-D Injection )

Figure 11: Graph high spots relationship between Absorbance and Wavelength ( nm ) of Cara-In-D Injection in three different intervals ( Batch 001, 002 and 003 ) .

( a ) At 0 month ( Batch No:001 ) .

( B ) At 3 month ( Batch No:001 ) .

( degree Celsius ) At 6 month ( Batch No:001 ) .

( vitamin D ) At 0 month ( Batch No:002 ) .

( vitamin E ) At 3 month ( Batch No:002 ) .

( degree Fahrenheit ) At 6 month ( Batch No:002 ) .

( g ) At 0 month ( Batch No:003 ) .

( H ) At 3 month ( Batch No:003 ) .

( I ) At 6 month ( Batch No:003 ) .

Table 10: Comparative Accelerated Stability Studies of Different Brands of Cholecalciferol ( Vitamin D3 ) Tablets.

Chapter NO 5

Statistical GLOSSARY:

OR

“ It is the least/minimum most value, for the survey concerned “ that differentiate between the critical and acceptance part.

Significance degree:

The standard used for rejecting the void hypothesis is called significance degree. The 0.05 or 5 % value is significance degree.

Standard divergence:

The descriptive statistic, in which there is a step of scattering, or spread, of sample informations around the mean and all the informations in a sample is used is called as Standard divergence.

Variable:

It is the thing measured, counted, or identified, the thing of involvement. It is the cardinal component of a statistical analysis. e.g. , Birth weight of a newborn baby, the clip a clock fails or practically any definable measure.

Note:

I used Minitab 15 Statistical package for my Research information analysis by using two manner ANOVA trial.

STATISTICAL DATA OF ACCELERATED STABILITY STUDY OF VITAMIN D3 ( CHOLECALCIFEROL ) TABLETS AND INJECTIONS:

Statistical Data of Accelerated Stability Studies of Qalsan D Tablets in Two-way ANOVA: Responses versus Months, batches ( Based on Assay consequence )

Beginning DF SS MS F P

Calendar months 2 3.7727 1.88634 14.75 0.014

Batchs 2 9.6977 4.84884 37.90 0.003

Mistake 4 0.5117 0.12793

Entire 8 13.9821

S = 0.3577 R-Sq = 96.34 % R-Sq ( adj ) = 92.68 %

Individual 95 % CIs For Mean Based on Pooled StDev

Calendar months Mean -+ — — — — -+ — — — — -+ — — — — -+ — — — —

0 101.493 ( — — — -* — — — – )

3 100.497 ( — — — — * — — — – )

6 99.927 ( — — — — * — — — – )

-+ — — — — -+ — — — — -+ — — — — -+ — — — —

99.40 100.10 100.80 101.50

Individual 95 % CIs For Mean Based on Pooled StDev

Batchs Mean -+ — — — — -+ — — — — -+ — — — — -+ — — — —

1 100.443 ( — — * — — – )

2 101.997 ( — — -* — — – )

3 99.477 ( — — -* — — – )

-+ — — — — -+ — — — — -+ — — — — -+ — — — —

99.0 100.0 101.0 102.0

Consequences: Here, I have observed a p value of 0.014 for the mean analysis of the affects of different methods for months. In this conditional chance, if my hypothesis is true, reveals that three methods significantly differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is much less than 0.05.

In this research, I have besides observed a p value of 0.003 for the mean analysis of the affects of different methods for batches. In this conditional chance, if my hypothesis is true, reveals that three methods significantly differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is much less than 0.05.

Statistical Data of Accelerated Stability Studies of Indrop D Injection in Two-way ANOVA: Responses versus Months, Batches ( Based on Assay consequence )

Beginning DF SS MS F P

Calendar months 2 2.77416 1.38708 11.47 0.022

Batchs 2 2.96176 1.48088 12.24 0.020

Mistake 4 0.48378 0.12094

Entire 8 6.21969

S = 0.3478 R-Sq = 92.22 % R-Sq ( adj ) = 84.44 %

Individual 95 % CIs For Mean Based on

Pooled StDev

Calendar months Mean — — -+ — — — — -+ — — — — -+ — — — — -+ — —

0 100.943 ( — — — -* — — — – )

3 100.000 ( — — — -* — — — – )

6 99.623 ( — — — -* — — — – )

— — -+ — — — — -+ — — — — -+ — — — — -+ — —

99.40 100.10 100.80 101.50

Individual 95 % CIs For Mean Based on

Pooled StDev

Batchs Mean — — — + — — — — -+ — — — — -+ — — — — -+ — –

1 100.070 ( — — — -* — — — – )

2 100.943 ( — — — -* — — — – )

3 99.553 ( — — — -* — — — – )

— — — + — — — — -+ — — — — -+ — — — — -+ — –

99.40 100.10 100.80 101.50

Consequences: Here, I have observed a p value of 0.022 for the mean analysis of the affects of different methods for months. In this conditional chance, if my hypothesis is true, reveals that three methods significantly differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is much less than 0.05.

In this research survey, I have besides observed a p value of 0.020 for the mean analysis of the affects of different methods for batches. In this conditional chance, if my hypothesis is true, reveals that three methods significantly differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is much less than 0.05.

Statistical Data of Accelerated Stability Studies of Osam-D Tablets in Two-way ANOVA: Responses versus Months, Batches ( Based on Assay consequence )

Beginning DF SS MS F P

Calendar months 2 75.0064 37.5032 16.61 0.012

Batchs 2 5.8756 2.9378 1.30 0.367

Mistake 4 9.0290 2.2572

Entire 8 89.9110

S = 1.502 R-Sq = 89.96 % R-Sq ( adj ) = 79.92 %

Individual 95 % CIs For Mean Based on

Pooled StDev

Calendar months Mean — — — + — — — — -+ — — — — -+ — — — — -+ — –

0 103.613 ( — — — -* — — — – )

3 99.857 ( — — — -* — — — – )

6 96.547 ( — — — -* — — — – )

— — — + — — — — -+ — — — — -+ — — — — -+ — –

96.0 99.0 102.0 105.0

Individual 95 % CIs For Mean Based on

Pooled StDev

Batchs Mean — — -+ — — — — -+ — — — — -+ — — — — -+ — —

1 101.147 ( — — — — — -* — — — — — – )

2 99.383 ( — — — — — -* — — — — — – )

3 99.487 ( — — — — — -* — — — — — – )

— — -+ — — — — -+ — — — — -+ — — — — -+ — —

98.0 100.0 102.0 104.0

Consequences: Here, I have observed a p value of 0.012 for the mean analysis of the affects of different methods for months. In this conditional chance, if my hypothesis is true, reveals that three methods significantly differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is much less than 0.05.

In this stableness survey, I have besides observed a p value of 0.367 for the mean analysis of the affects of different methods for batches. In this conditional chance, if my hypothesis is false, reveals that three methods significantly non differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is much greater than 0.05.

Statistical Data of Accelerated Stability Studies of ED-3 Injection in Two-way ANOVA: Responses versus Months, Batches ( Based on Assay consequence )

Beginning DF SS MS F P

Calendar months 2 75.0064 37.5032 16.61 0.012

Batchs 2 5.8756 2.9378 1.30 0.367

Mistake 4 9.0290 2.2572

Entire 8 89.9110

S = 1.502 R-Sq = 89.96 % R-Sq ( adj ) = 79.92 %

Individual 95 % CIs For Mean Based on

Pooled StDev

Calendar months Mean — — — + — — — — -+ — — — — -+ — — — — -+ — –

0 103.613 ( — — — -* — — — – )

3 99.857 ( — — — -* — — — – )

6 96.547 ( — — — -* — — — – )

— — — + — — — — -+ — — — — -+ — — — — -+ — –

96.0 99.0 102.0 105.0

Individual 95 % CIs For Mean Based on

Pooled StDev

Batchs Mean — — -+ — — — — -+ — — — — -+ — — — — -+ — —

1 101.147 ( — — — — — -* — — — — — – )

2 99.383 ( — — — — — -* — — — — — – )

3 99.487 ( — — — — — -* — — — — — – )

— — -+ — — — — -+ — — — — -+ — — — — -+ — —

98.0 100.0 102.0 104.0

Consequences: Here, I have observed a p value of 0.012 for the mean analysis of the affects of different methods for months. In this conditional chance, if my hypothesis is true, reveals that three methods significantly differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is much less than 0.05.

In this research instance, I have besides observed a p value of 0.367 for the mean analysis of the affects of different methods for batches. In this conditional chance, if my hypothesis is false, reveals that three methods significantly non differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is much higher than 0.05.

Statistical Data of Accelerated Stability Studies of Calgo Tablets in Two-way ANOVA: Responses versus Months, Batches ( Based on Assay consequences )

Beginning DF SS MS F P

Calendar months 2 92.917 46.4586 12.42 0.019

Batchs 2 33.250 16.6252 4.45 0.096

Mistake 4 14.961 3.7402

Entire 8 141.128

S = 1.934 R-Sq = 89.40 % R-Sq ( adj ) = 78.80 %

Individual 95 % CIs For Mean Based on

Pooled StDev

Calendar months Mean — — — -+ — — — — -+ — — — — -+ — — — — -+ —

0 107.970 ( — — — -* — — — – )

3 104.537 ( — — — * — — — – )

6 100.120 ( — — — * — — — – )

— — — -+ — — — — -+ — — — — -+ — — — — -+ —

100.0 104.0 108.0 112.0

Individual 95 % CIs For Mean Based on Pooled StDev

Batchs Mean + — — — — -+ — — — — -+ — — — — -+ — — — — –

1 102.180 ( — — — — — * — — — — – )

2 103.657 ( — — — — — * — — — — – )

3 106.790 ( — — — — -* — — — — – )

+ — — — — -+ — — — — -+ — — — — -+ — — — — –

99.0 102.0 105.0 108.0

Consequences: Here, I have observed a p value of 0.019 for the mean analysis of the affects of different methods for months. In this conditional chance, if my hypothesis is true, reveals that three methods significantly differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is much less than 0.05.

In this instance of research survey, I have besides observed a p value of 0.096 for the mean analysis of the affects of different methods for batches. In this conditional chance, if my hypothesis is incorrect, reveals that three methods significantly non differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is greater than 0.05.

Statistical Data of Accelerated Stability Studies of Cara-In- D Injection in Two-way ANOVA: Responses versus Months, Batches ( Based on Assay consequence )

Beginning DF SS MS F P

Calendar months 2 92.917 46.4586 12.42 0.019

Batchs 2 33.250 16.6252 4.45 0.096

Mistake 4 14.961 3.7402

Entire 8 141.128

S = 1.934 R-Sq = 89.40 % R-Sq ( adj ) = 78.80 %

Individual 95 % CIs For Mean Based on

Pooled StDev

Calendar months Mean — — — -+ — — — — -+ — — — — -+ — — — — -+ —

0 107.970 ( — — — -* — — — – )

3 104.537 ( — — — * — — — – )

6 100.120 ( — — — * — — — – )

— — — -+ — — — — -+ — — — — -+ — — — — -+ —

100.0 104.0 108.0 112.0

Individual 95 % CIs For Mean Based on Pooled StDev

Batchs Mean + — — — — -+ — — — — -+ — — — — -+ — — — — –

1 102.180 ( — — — — — * — — — — – )

2 103.657 ( — — — — — * — — — — – )

3 106.790 ( — — — — -* — — — — – )

+ — — — — -+ — — — — -+ — — — — -+ — — — — –

99.0 102.0 105.0 108.0

Consequences: Here, I have observed a p value of 0.019 for the mean analysis of the affects of different methods for months. In this conditional chance, if my hypothesis is true, reveals that three methods significantly differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is much less than 0.05.

In this survey, I have besides observed a p value of 0.096 for the mean analysis of the affects of different methods for batches. In this conditional chance, if my hypothesis is false, reveals that three methods significantly non differ from each other in giving the response for the understudy check consequence. My was set at 0.05 and the P value “ the ascertained “ is much higher than 0.05.

Table 12: Parameters of the Statistical analysis of consequences in finding of assay content of Cholecalciferol ( Vitamin D3 ) Tablets during Accelerated Stability Study conditions.

Statistical HYPOTHESIS TESTING DATA ( MONTHS AND BATCHES )

a. Statistical hypothesis proving Data of Qalsan D Tablets ( Months ) .

B. Statistical hypothesis proving Data of Qalsan D Tablets ( Batches ) .

c. Statistical hypothesis proving Data of Calgo Tablets ( Months ) .

d. Statistical hypothesis proving Data of Calgo Tablets ( Batches ) .

f. Statistical hypothesis proving Data of Indrop D Injection ( Months ) .

f. Statistical hypothesis proving informations of Osam-D Tablets ( Batches ) .

Statistical hypothesis proving informations of Indrop D injection ( Batches ) .

Statistical hypothesis proving informations of Osam-D Tablets ( Months ) .

Statistical hypothesis proving informations of ED-3 Injection ( Months ) .

Statistical hypothesis proving informations of ED-3 Injection ( Batches ) .

Statistical hypothesis proving informations of Cara-In-D Injection ( Months ) .

Statistical hypothesis proving informations of Cara-In-D Injection ( Batches ) .

Chapter NO 6

RESULTS AND DISCUSSIONS:

Three trade names of Cholecalciferol ( Vitamin D3 ) tablets i.e. , ( a ) Qalsan D, ( B ) Calgo and ( degree Celsius ) Osam-D incorporating 125, 125 and 400 IU severally of Cholecalciferol were used in this survey.

Qalsan D tablet in record of assay content had no debasement observed and was stable at temperature 40A±2 oC and Relative humidity75A±5 % while Osam-D and Calgo in record of assay content show small bit debasement at given accelerated stableness survey parametric quantities.

The trade names of Cholecalciferol tablets were found to follow with the Pharmacopoeial demands as shown in tabular array ( 10 ) as respects to their fluctuation in assay contents, hardness, crumbliness, decomposition and wet content.

The check content trials of tablet were carried out by utilizing methyl alcohol as space, formic acid and dinitrophenylhydrazin supply by dependable beginnings at EZmax 265nm, utilizing Double beam UV Spectrophotometer.

The per centum of Qalsan D tablet samples of Batch 001, 002, 003 were analyzed and checked at month ( 0, 3, 6 ) at specific temperature and comparative humidness. Graph was plotted between wavelength and optical density as shown in figure ( 6 ) .

From assay content behaviour of these Cholecalciferol tablets, it is apparent from table ( 10 ) , ASS information and figure ( 6 ) that in first 6 months of Batch 001, consequences decreased from 100.89 % to 100 % . In Batch 002, holding 6 months survey, consequences illustrated downward status from 102.92 % to 101.35 % , while in Batch 003 holding 6 months ASS, consequence move from 100.67 % to 98.43 % .

Similarly both “ P ” values of Qalsan D tablets were placed within the bound i.e. , NMT 0.05, as shown in statistical informations.

The per centum of Calgo tablet samples of Batch 001, 002, 003 were analyzed and checked at month ( 0, 3, 6 ) at specific temperature and comparative humidness. Graph was plotted between wavelength and optical density as shown in figure ( 7 ) .

From assay content behaviour of these Cholecalciferol tablets, it is apparent from table ( 10 ) , ASS information and figure ( 7 ) that in first 6 months of Batch 001, consequences decreased from 105.63 % to 98.19 % . In Batch 002, holding 6 months survey, consequences illustrated downward status from 107.79 % to 97.50 % , while in Batch 003 holding 6 months ASS, consequence move from 110.49 % to 104.67 % .

Similarly out of two “ P ” values, one “ P ” value of Calgo tablets was out of the bound while other meets the demand, i.e. , NMT 0.05, as shown in statistical informations.

The per centum of Osam-D tablet samples of Batch 001, 002, 003 were analyzed and checked at month ( 0, 3, 6 ) at specific temperature and comparative humidness. Graph was plotted between wavelength and optical density as shown in figure ( 7 ) .

From assay content behaviour of these Cholecalciferol tablets, it is apparent from table ( 10 ) , ASS information and figure ( 8 ) that in first 6 months of Batch 001, consequences decreased from 104.54 % to 96.18 % . In Batch 002, holding 6 months survey, consequences illustrated downward status from 102.69 % to 97.27 % , while in Batch 003 holding 6 months ASS, consequence move from 103.61 % to 96.19 % .

Similarly out of two “ P ” values, one “ P ” value of Osam-D tablets was out of the bound while other meets the demand, i.e. , NMT 0.05, as shown in statistical informations.

In 2nd survey, three trade names of Cholecalciferol ( Vitamin D3 ) injections i.e. , ( a ) Indrop D, ( B ) ED-3 and ( degree Celsius ) Cara-In-D incorporating 200,000 IU/1ml ( 5mg/1ml ) each of Cholecalciferol were used.

Indrop D in record of assay content show no debasement and was stable at temperature 40A±2 oC and Relative humidity75A±5 % while ED-3 and ED-3 and Cara-In-D injection in record of assay content show debasement and were unstable at temperature 40A±2 oC and Relative humidity75A±5 % .

The trade names of Cholecalciferol injections were found to follow with the Pharmacopoeial demands as shown in tabular array ( 11 ) as respects to their fluctuation in assay contents.

The check content trials of injections were carried out by utilizing methyl alcohol as space, formic acid and dinitrophenylhydrazin supply by dependable beginnings at EZmax 265nm, utilizing Double beam UV Spectrophotometer.

The per centum of Indrop D tablet samples of Batch 001, 002, 003 were analyzed and checked at month ( 0, 3, 6 ) at specific temperature and comparative humidness. Graph was plotted between wavelength and optical density as shown in figure ( 9 ) .

From assay content behaviour of these Cholecalciferol injections, it is apparent from table ( 11 ) , ASS information and figure ( 9 ) that in first 6 months of Batch 001, consequences decreased from 100.44 % to 99.77 % . In Batch 002, holding 6 months survey, consequences illustrated downward status from 100.44 % to 101.35 % , while in Batch 003 holding 6 months ASS, consequence move from 100.67 % to 98.66 % .

Similarly two “ P ” values of Indrop D were placed within the bound, i.e. , NMT 0.05, as shown in statistical informations.

The per centum of ED-3 injection samples of Batch 001, 002, 003 were analyzed and checked at month ( 0, 3, 6 ) at specific temperature and comparative humidness. Graph was plotted between wavelength and optical density as shown in figure ( 10 ) .

From assay content behaviour of these Cholecalciferol injections, it is apparent from table ( 11 ) , ASS information and figure ( 10 ) that in first 6 months of Batch 001, consequences decreased from 104.54 % to 96.18 % . In Batch 002, holding 6 months survey, consequences illustrated downward status from 102.69 % to 97.27 % , while in Batch 003 holding 6 months ASS, consequence move from 103.61 % to 96.19 % .

Similarly out of two “ P ” values, one “ P ” value of ED-3 injection was out of the bound while other meets the demand, i.e. , NMT 0.05, as shown in statistical informations.

The per centum of Cara-In-D injection samples of Batch 001, 002, 003 were analyzed and checked at month ( 0, 3, 6 ) at specific temperature and comparative humidness. Graph was plotted between wavelength and optical density as shown in figure ( 11 ) .

From assay content behaviour of these Cholecalciferol injections, it is apparent from table ( 11 ) , ASS information and figure ( 11 ) that in first 6 months of Batch 001, consequences decreased from 105.63 % to 98.19 % . In Batch 002, holding 6 months survey, consequences illustrated downward status from 107.79 % to 97.50 % , while in Batch 003 holding 6 months ASS, consequence move from 110.49 % to 104.67 % .

Similarly out of two “ P ” values, one “ P ” value of Cara-In-D injections was out of the bound while other meets the demand, i.e. , NMT 0.05, as shown in statistical informations.

Mentioning to different assay consequences in table ( 10 ) and ( 11 ) of Cholecalciferol tablets and injections, the difference in the rates of assay content can be about be explained on the footing of oxidative debasement of Cholecalciferol, since nature of Cholecalciferol debasement is unknown ( Hoffmann-La-Roche, 1989 ) .

Therefore, the stableness is merely explained by transporting out the check for Cholecalciferol after storage under the chosen exaggerated conditions.

This behaviour of debasement from four trade names of Cholecalciferol suggests that in these peculiar environmental conditions i.e. , temperature 40A±2 oC and Relative humidity75A±5 % affect the quality of Cholecalciferol molecule.

In first instance, Qalsan D tablet has stable Cholecalciferol molecule while, Calgo and Osam D tablet required particular attending from the start of fabricating up to concluding packaging.

In 2nd instance of survey, Indrop D has stable Cholecalciferol molecule while ED-3 and Cara-In-D injection require particular attention during fabricating from first measure to last one.

In our surveies, we confirmed the old findings that Cholecalciferol ( Vitamin D3 ) degrades quickly at high temperatures and comparative humidness. The fastest debasement occurs at the combination of elevated temperature and high comparative humidness, when all samples degraded within several yearss.

Chapter NO 7

CONCLUSIONS AND SUGGESTIONS:

Decision:

From consequences and their treatment, the chief decisions of the present probe on the accelerated stableness survey of different trade names of Cholecalciferol tablets and injections may be summarized as follows:

The stableness of the Cholecalciferol was investigated under assorted conditions. Cholecalciferol tablet and injection samples were found to be sensitive to elevated temperatures every bit good as to high comparative humidness. The most stable signifier is obtained in Qalsan D tablet and Indrop D injection preparations.

The Qalsan D tablet and Indrop D injection have stable Cholecalciferol molecule for 2 old ages while debasement of Cholecalciferol in Calgo tablet, Osam-D tablet, ED-3 injection and Cara-In-D injection highlight unstability of molecule under emphasis conditions and should be degraded wholly before 2 old ages.

The difference in assay contents with the advancement of month and batch can be explained on the footing of oxidative debasement phenomenon.

Lowering of assay consequence and alteration in construction of molecule are basic research accelerated stableness consequences for antioxidant like Cholecalciferol.

Three trade names of tablets, consequently of the grade of oxidative debasement of Cholecalciferol are arranged in following sequence:

Qalsan D aˆ? Osam-D aˆ? Calgo

Three trade names of injections, consequently of the grade of oxidative debasement of Cholecalciferol are arranged in following sequence:

Indrop D aˆ? ED-3 aˆ? Cara-In-D

Suggestion:

Some of the most complex preparations include tablet and parenteral vitamins/multivitamins readyings. These may be exposed to temperature and comparative humidness during fabrication, storage, and disposal doing vitamin interaction and loss of the single vitamins. Since Cholecalciferol is peculiarly sensitive to temperature and humidness and is usually present in micro measures, its loss even in little sums may strip the patient of the needed dosage of the vitamin.

In position of the sensitiveness of Cholecalciferol and the influence of factors such as temperature, comparative humidness, visible radiation, O degree and wavelength, presence of other vitamins, in a multivitamin readying, or active/excipients of drug merchandise, an rating of stableness features of Cholecalciferol highly hard. Therefore, the attack adopted in this survey work to simplify the system ab initio to binary mixtures can function as a theoretical account for farther surveies.

This may be used to carry on further systematic surveies on the rating of Cholecalciferol stableness in tablets and injections mixtures.

Designation of the unknown oxidization merchandises of Cholecalciferol in tablet and injection.

Survey of the relationship of debasement rates with temperature and comparative humidness in a peculiar medium and anticipation of normal shelf-life of Vitamin D3 tablet and injection.

Development of Stability-determining methods for the check of a Cholecalciferol in the presence of its debasement merchandise.

Survey of the relationship of debasement rates with viscousness of parenteral medium.

Survey of the relationship of debasement rates of vitamin D3 with dielectric invariable of the medium.

Survey of the debasement rates of Cholecalciferol utilizing different parametric quantities suggested above under anaerobiotic conditions.

Survey of the relationship of debasement rates with Non-Pharmacopoeial methods applied during analysis of Cholecalciferol tablet and injection.

Chapter NO 8