COLLEGE OF PHARMACY DEPARTMENT OF ... OF PHARMACY DEPARTMENT OF PHARMACEUTICS LABORATORY MANUAL...

PRINCE SATTAM BIN ABDULAZIZ UNIVERSITY

COLLEGE OF PHARMACY

DEPARTMENT OF PHARMACEUTICS

LABORATORY MANUAL

PHARMACEUTICS IV

PHT-414

LEVEL VII

EXPERIMENTAL COORDINATOR -

Dr. MUQTADER MOHAMMED

Email:- [email protected]

Academic Year 2016-17

Semester II

PSAU-COP, Al-Kharj- KSA

mailto:mo.ahmed@psau

1

P PRESENT

A ABSENT

E EXCUSED

G GROUP – EXPERIMENT PERFORMED IN GROUP

S SINGLE- EXPERIMENT PERFORMED INDIVIDUALLY

C EXPERIMENT COMPLETED

I EXPERIMENT INCOMPLETE

A EXCELLENT

G GOOD

C POOR

Sl.

no

Content &

Learning outcomes

EVALUATIONS pag

e# Attendance Performance Worksheet GLP

P A E G S C I A B C

1 PH Partition Theory, , you will be able to

calculate and determine the partition coefficient.

3 Disintegration , study of disintegration time for

different type of tablet formulations.

3.2 Disintegration of uncoated tablets.

3.3 Disintegration of coated tablets.

3.4 Disintegration of enteric coated tablets.

4 Drug Dissolution time profile study.

4.1 Drug dissolution of Paracetamol/Acetaminophen

tablet marketed formulation.

4.2 Drug dissolution of ciprofloxacin tablet

marketed formulation

5 Enhancement of solubility by preparation of

solid dispersion techniques.

5.1 Preparation of solid dispersion by physical

mixture method.

5.2 Preparation of solid dispersion by solvent

evaporation techniques.

6 Influence of vehicle on the solubility of

Ciprofloxacin HCl.

7 Demonstration of in-vitro diffusion study of

Tran dermal drug delivery systems.

2

CERTIFICATE OF LAB PERFORMANCE

SL# ACTIVITY NAME A B C

1.

2.

3.

4.

5.

Sl.

no

Content &

Learning outcomes

EVALUATIONS Attendance Performance Worksheet GLP

P A E G S C I A B C

1 PH Partition Theory, , you will be able to

calculate and determine the partition coefficient.

3 Disintegration , study of disintegration time for

different type of tablet formulations.

3.2 Disintegration of uncoated tablets.

3.3 Disintegration of coated tablets.

3.4 Disintegration of enteric coated tablets.

4 Drug dissolution time profile study.

4.1 Drug dissolution of Paracetamol/Acetaminophen

tablet marketed formulation.

4.2 Drug dissolution of ciprofloxacin tablet

marketed formulation

5 Enhancement of solubility by preparation of

solid dispersion techniques.

5.1 Preparation of solid dispersion by physical

mixture method.

5.2 Preparation of solid dispersion by solvent

evaporation techniques.

6 Influence of vehicle on the solubility of

Ciprofloxacin HCl.

7 Demonstration of in-vitro diffusion study of

Tran dermal drug delivery systems.

Marks Awarded:

3

Introduction & grading about the Course Outline

Pharmaceutics IV: PHT-414

Grading

Final Exam 15

Viva/synopsis/other activities 5

Record, GLP, ACTIVITIES 5

Total 25

4

Partition Coefficient

Practical-1: Date

Aim:

Determination of the Partition Coefficient of Citric Acid (drug) between Water (aqueous phase) and 2-Methylpropan-1-ol (isobutyl alcohol) (non aqueous phase).

Introduction

If a solute is added to two immiscible solvents, A and B. in contact with each other, the solute distributes itself between the two and equilibrium is set up between the solute molecules in solvent A and the solute molecules in solvent B. The ratio of the concentration of the solute in the two solvents is

where K is known as the partition coefficient or distribution coefficient.

Chemicals

2-Methylpropan-1-ol (density = 0.805 gdm-3), 0.2 M Citric acid (drug already dissolved in the aqueous phase – water), 0.1 M NaOH, phenolphthalein indicator

Apparatus

100 ml separating funnel, titration apparatus, 5 ml pipette

Procedure

1. Record the room temperature.

2. Using suitable apparatus pour 25 ml of the 0.2 M Citric acid solution and 25 ml of 2-methylpropan-1-ol into a 100 cm3 separating funnel. Stopper the funnel and shake vigorously for 6 minutes. (Release pressure in the funnel by occasionally opening the tap.)

3. Separate approximately 15 ml of EACH layer and collect them in TWO

clean beakers. (Discard the fraction near the junction of the two layers.)

4. Pipette 5 ml of the aqueous layer into a titration flask and titrate it with 0.1 M sodium hydroxide solution using 2 drops of phenolphthalein indicator.

5. Using another pipette, deliver 5 ml of the non-aqueous layer into a

titration flask and titrate it with 0.1 M sodium hydroxide solution using 2 drops of phenolphthalein indicator.

5

Observation :

Trial Volume of 0.1 M NaOH

titre for aqueous layer/

cm3

Volume of 0.1 M

NaOH titre for non-

aqueous layer/ cm3

Calculation:

M1V1=M2V2

M1(UNKNOWN MOLARITY/ CONC), V1( VOLUME IN CONICAL FLASK)

M2( MOL OF BUREETE SOLUTION ), V2(VOL CONSUMED IN TITRATION)

FOR NON-AQUOUS LAYER

M1= M2V2

V1

FOR AQUOUS LAYER

M1= M2V2

V1

7. For each experiment, calculate the ratio of the concentration of citric acid in the non-aqueous layer in relation to the aqueous layer.

If calculated Partition Coefficient: K = O/W is ≤ 10 relatively hydrophilic, K = O/W

is ≥ 104

Hydrophobic in nature.

Concentration of solute

(unknown)

M1

In aqueous layer

In non-aqueous layer

6

Report : The partition coefficient for the given drug sample was found to be ________ . Inference : As per the result the compound was found to be hydrophilic / hydrophobic in nature.

Student ID / Reg No

Comment on your results.

********************************

7

Exp.No: Date:

Effect of pH on the Partition Coefficient of acidic and basic drugs

Aim

Determination of the effect of pH on Partition Coefficient of Citric Acid (drug)

between (aqueous phase) and 2-Methylpropan-1-ol (isobutyl alcohol) (non

aqueous phase).

Introduction (pH - Partition Theory)

For a drug to cross a membrane barrier it must normally be soluble in the

lipid material of the membrane to get into membrane it has to be soluble in the

aqueous phase as well to get out of the membrane. Many drugs have polar and non-

polar characteristics or are weak acids or bases. For drugs which are weak acids or

bases the pKa of the drug, the pH of the GI tract fluid and the pH of the blood

stream will control the solubility of the drug and thereby the rate of absorption

through the membranes lining the GI tract.

Brodie et al. stated that when a drug is ionized it will not be able to get through the

lipid membrane, but only when it is non-ionized and therefore has higher lipid

solubility.

Chemicals

2-Methylpropan-1-ol (density = 0.805 gdm-3), 0.2 M Citric acid (drug already

dissolved in the aqueous phase – Buffer solutions with different pH ), 0.1 M NaOH,

phenolphthalein indicator

Apparatus

100 ml separating funnel, titration apparatus, 5 ml pipette

8

Procedure

1. Record the room temperature.

2. Using suitable apparatus pour 25 ml of the 0.2 M Citric acid solution and

25 ml of 2-methylpropan-1-ol into a 100 cm3 separating funnel.

Stopper the funnel and shake vigorously for 6 minutes. (Release pressure in

the funnel by occasionally opening the tap.)

3. Separate approximately 15 ml of EACH layer and collect them in TWO

clean beakers. (Discard the fraction near the junction of the two layers.)

4. Pipette 5 ml of the aqueous layer into a titration flask and titrate it with 0.1 M

sodium hydroxide solution using 2 drops of phenolphthalein indicator.

5. Using another pipette, deliver 5 ml of the non-aqueous layer into a

titration flask and titrate it with 0.1 M sodium hydroxide solution using 2

drops of phenolphthalein indicator.

6. Repeat steps (2) to (5) with another separating funnel using either one of

the following as aqueous solutions

a. Acetate buffer pH 4.5

b. Phosphate buffer Ph 7.2 Observation

Trial Buffer (pH) Volume of 0.1 M NaOH

titre for aqueous layer/

cm3

Volume of 0.1 M

NaOH titre for non-

aqueous layer/ cm3

9

Calculation:

M1V1=M2V2

M1(UNKNOWN MOLARITY/ CONC), V1( VOLUME IN CONICAL FLASK)

M2( MOL OF BUREETE SOLUTION ), V2(VOL CONSUMED IN

TITRATION)

FOR NON-AQUOUS LAYER

M1= M2V2

V1

FOR AQUOUS LAYER

M1= M2V2

V1

7. For each experiment, calculate the ratio of the concentration of citric acid in

the non-aqueous layer in relation to the aqueous layer.

If calculated Partition Coefficient: K = O/W is ≤ 10 relatively hydrophilic, K = O/W is ≥ 10

4 Hydrophobic in nature.

Increase in P

H increases or decreases the Partition Coefficient

Report: The partition coefficient for the given drug sample was found to be ________ . Inference : As per the result the compound was found to be hydrophilic / hydrophobic in nature and the effect of P

H was found to

be_____________________________________________

Concentration of solute

(unknown)

M1

In aqueous layer

In non-aqueous layer

PH =

10

Student ID / Reg No


Report:

###############

11

Disintegration & Dissolution

Both tests are a measure of Wetting – How quickly the tablet is exposed to the media

Disintegration – the speed and nature of particle release

Dissolution- the speed and nature of API dissolved

12

DISINTEGRATION TEST

Introduction:

The disintegration test is a measure of the time required under a given set of conditions for a

group of tablets to disintegrate into particles which will pass through a 10 mesh screen.

Generally, the test is useful as a quality assurance tool for conventional dosage forms.

Apparatus

The apparatus consists of a basket-rack assembly, a 1000 mL, low-form beaker, 138-160 mm

in height and having an inside diameter of 97-115 mm for the immersion fluid, a thermostatic

arrangement for heating the fluid between 35 °C and 39 °C, and a device for raising and

lowering the basket in the immersion fluid at a constant frequency rate between 29 and 32

cycles per minute, through a distance of not less than 53 mm and not more than 57 mm. The

volume of the fluid in the vessel is such that at the highest point of the upward stroke the wire

mesh remains at least 15 mm below the surface of the fluid and descends to not less than 25

mm from the bottom of the vessel on the downward stroke. At no time should the top of the

basket-rack assembly become submerged. The time required for the upward stroke is equal to

the time required for the downward stroke and the change in stroke direction is a smooth

transition, rather than an abrupt reversal of motion. The basket-rack assembly moves vertically

along its axis. There is no appreciable horizontal motion or movement of the axis from the

vertical.

Basket-rack assembly

The basket-rack assembly consists of six open-ended transparent tubes, each 75.0-80.0 mm

long and having an internal diameter of 20.70-23.00 mm and a wall 1.0-2.8 mm thick; the

tubes are held in a vertical position by two plates, each 88-92 mm in diameter and 5.00-8.50

mm in thickness, with six holes, each 22-26 mm in diameter, equidistant from the centre of the

plate and equally spaced from one another. Attached to the lower surface of the lower plate is

a woven stainless steel wire mesh, which has a plain square weave with 1.8-2.2 mm apertures

and with a wire diameter of 0.570-0.660 mm. The parts of the apparatus are assembled and

rigidly held by means of three bolts passing through the two plates. A suitable means is

provided to suspend the basket-rack assembly from the raising and lowering device using a

point on its axis.

The design of the basket-rack assembly may be varied somewhat provided the specifications

for the glass tubes and the screen mesh size are maintained. The basket-rack assembly

conforms to the dimensions shown in Figure 1.

Discs

The use of discs is permitted only where specified or allowed. Each tube is provided with a

cylindrical disc 9.35-9.65 mm thick and 20.55-20.85 mm in diameter. The disc is made of a

suitable, transparent plastic material having a specific gravity of 1.18-1.20. Five parallel 1.9-

2.1 mm holes extend between the ends of the cylinder. One of the holes is centered on the

cylindrical axis. The other holes are centered 5.8-6.2 mm from the axis on imaginary lines

perpendicular to the axis and parallel to each other. Four identical trapezoidal-shaped planes

are cut into the wall of the cylinder, nearly perpendicular to the ends of the cylinder. The

trapezoidal shape is symmetrical; its parallel sides coincide with the ends of the cylinder and

are parallel to an imaginary line connecting the centres of two adjacent holes 6 mm from the

cylindrical axis. The parallel side of the trapezoid on the bottom of the cylinder has a length of

1.5-1.7 mm and its bottom edges lie at a depth of 1.50-1.80 mm from the cylinder’s

circumference. The parallel side of the trapezoid on the top of the cylinder has a length of 9.2-

13

9.6 mm and its centre lies at a depth of 2.5-2.7 mm from the cylinder’s circumference. All

surfaces of the disc are smooth. If the use of discs is specified, add a disc to each tube and

operate the apparatus as directed under procedure. The discs conform to the dimensions found

in Figure 1.

The use of automatic detection employing modified discs is permitted where the use of discs is

specified or allowed. Such discs must comply with the requirements of density and dimension

given in this chapter.

Procedure

Place one dosage unit in each of the six tubes of the basket and if specified add a disc. Operate

the apparatus using water as the immersion fluid unless another liquid is specified and

maintain its temperature at 35-39 °C. At the end of the specified time, lift the basket from the

fluid and observe the dosage units: all of the dosage units have disintegrated completely. If

one or two dosage units fail to disintegrate, repeat the test on 12 additional dosage units. The

requirements of the test are met if not less than 16 of the 18 dosage units tested are

disintegrated.

14

Figure 1. Diagram for disintegration apparatus

(dimensions are expressed in millimeters)

15

FORMULATION INDIAN PHARMACOPOEIA 1996 (IP) BRITISH PHARMACOPOEIA 2009 (BP)

UNITED STATES

PHARMACOPOEIA 2009

(USP)

Uncoated ed tablets

Uses disintegration apparatus with 250ml or 1 L

of specified medium & for specified time as

per monograph. If 1-2 fail, repeat for 12

different units. 16 out of 18 indicate test is

affirmative.

Uses disintegration apparatus Uses liquid medium

water R or specified medium for 15 min. If 1-

2 fail, repeat for 12 different units. 16 out of

18 indicate test is affirmative.

Uses disintegration apparatus with specified

liquid medium & for specified time as

per monograph. If 1-2 fail, repeat for

12 different units. 16 out of 18

indicate test is affirmative.

Chewable tablets -NA- Disintegration test not applicable.

Same as uncoated tablets. Uses

disintegration apparatus with specified

liquid medium & for 4 hours or as per

monograph. If 1-2 fail, repeat for 12

different units. 16 out of 18 indicate

test is affirmative.

Non-film coated tablets -NA-

Uses disintegration apparatus with water R or

specified liquid medium & for 60 min., if

there is no cracking of coat; continue by

replacing the medium with 0.1 M HCl for

specified time as per monograph. If 1-2 fail,

repeat for 12 different units. 16 out of 18








Film coated tablets -NA-

Uses disintegration apparatus with water R or

specified liquid medium & for 30 min., if

there is no cracking of coat; continue by

replacing the medium with 0.1 M HCl for

specified time as per monograph. If 1-2 fail,

repeat for 12 different units. 16 out of 18








Gastro resistant tablets

(Enteric Coated)

Uses disintegration apparatus with 250ml or 1 L

of specified medium & for specified time as per

monograph. If 1-2 fail, repeat for 12 different

units. 16 out of 18 indicate test is affirmative.

Uses disintegration apparatus with 0.1 M HCl at

37+-2OC for 2-3 hrs (nlt 1 hour), if there is no

cracking or breaking of coat, continue with

phosphate buffer, pH 6.8 at same temperature for 1

hour or as per monograph. If 1-2 fail, repeat for 12


affirmative.

Uses disintegration apparatus with

stimulated gastric fluid TS at 37+-2OC for 1

hour, if there is no cracking or breaking of

coat, continue with stimulated intestinal

fluid at same temperature for specified time

as per monograph.If 1-2 fail, repeat for 12


affirmative.

http://www.usp.org/

16

Exp.No: Date:

Disintegration test of marketed formulations

Aim

To check the time of disintegration of given marketed formulations. The time of

disintegration is a measure of the quality. This is because, for example, if the

disintegration time is too high; it means that the tablet is too highly compressed or the

capsule shell gelatin is not of pharmacopoeial quality or it may imply several other

reasons. And also if the disintegration time is not uniform in a set of samples being

analysed, it indicates batch inconsistency and lack of batch uniformity.

Introduction

The apparatus consists of a basket made of transparent polyvinyl or other plastic

material. It has 6 tubes set into the same basket with equal diameter and a wire mesh

made of stainless steel with uniform mesh size is fixed to each of these six tubes.

Small metal discs may be used to enable immersion of the dosage form completely.

The entire basket-rack assembly is movable by reciprocating motor which is fixed to

the apex of the basket-rack assembly. The entire assembly is immersed in a vessel

containing the medium in which the disintegration test is to be carried out. The vessel

is provided with a thermostat to regulate the temperature of the fluid medium to the

desired temperature.

Chemicals & Formulation Any marketed tablet or capsule formulation except states that are intended for use as

troches, or are to be chewed, or are designed as extended-release dosage forms or

delayed-release dosage forms.

Apparatus Disintegration test apparatus and stop watch.

Procedure

1. Uncoated tablets- Tested using distilled water as medium at 37+/-2 C at 29-32

cycles per minute; test is completed after 15 minutes. It is acceptable when there is

17

no palpable core at the end of the cycle (for at least 5 tablets or capsules) and if the

mass does not stick to the immersion disc.

2. Coated tablets- the same test procedure is adapted but the time of operation is 30

minutes.

3. Enteric coated/ Gastric resistant tablets- the test is carried out first in distilled water

(at room temperature for 5 min.; USP and no distilled water per BP and IP), then it

is tested in 0.1 M HCL ( upto 2 hours; BP ) or Stimulated gastric fluid (1 hour;

USP) followed by Phosphate buffer, pH 6.8 (1 hour; BP) or Stimulated intestinal

fluid without enzymes (1 hour; USP).

4. Chewable tablets- exempted from disintegration test (BP and IP), 4 hours (USP).

Note: If 1 or 2 tablets fail to disintegrate completely, repeat the test on 12

additional tablets. The requirement is met if not fewer than 16 of the total of

18 tablets tested are disintegrated

Results

Trial Formulation Specified Time Result (minutes )

Report: disintigartion time of given tablet was found to be ______

Student ID / Reg No


18

Report:

19

DISSOLUTION OF MARKETED TABLET FORMULATION

This test determines the amount of active ingredient(s) released from a solid oral dosage

form, such as a tablet or a capsule, under controlled conditions using a known volume of

dissolution medium within a predetermined length of time.

Basket apparatus. The assembly consists of the following: a vessel, which may be

covered, made of glass or other inert, transparent material, which should not sorb, react

or interfere with the dosage form, the active ingredient or the dissolution medium; a

motor; a drive shaft; and a cylindrical basket. The vessel is partially immersed in a

suitable water-bath of any convenient size or heated by a suitable device such as a

heating jacket to maintain the temperature inside the vessel at 37 ± 0.5 ºC during the test

and to keep the dissolution medium in constant, smooth motion. No part of the assembly,

including the environment in which the assembly is placed, contributes significant

motion, agitation or vibration beyond that due to the smoothly rotating stirring element.

Apparatus that permits observation of the preparation and stirring element during the test

is preferable. The vessel is cylindrical, with a hemispherical bottom and a capacity of 1

litre. Its height is 160–210 mm and its inside diameter is 98 –106 mm. Its sides are

flanged at the top. A fitted cover may be used to retard evaporation. If a cover is used it

provides sufficient openings to allow ready insertion of the thermometer and withdrawal

of samples. The shaft is positioned so that its axis is not more than 2 mm at any point

from the vertical axis of the vessel and rotates smoothly and without significant wobble

that could affect the results. A speed-regulating device is used that allows the shaft

rotation speed to be selected and maintained at a specified rate within ± 4%.

Shaft and basket components of the stirring element are fabricated of stainless steel, type

316 or equivalent, to the specifications shown in Figure 1. A basket having a gold

coating of about 2.5 µm (0.0001 inch) thick may be used. The dosage unit is placed in a

dry basket at the beginning of each test. The distance between the inside bottom of the

vessel and the bottom of the basket is maintained at 25 ± 2 mm during the test.

Figure 1. Basket stirring element

Dimensions in millimetres

20

A and B dimensions do not vary more than 0.5 mm when part is rotated on centre line

axis. Tolerances are ± 1.0 mm unless otherwise stated.

Figure 2. Paddle stirring element.

Dimensions in millimetres

Paddle Apparatus. Use the assembly from Basket apparatus except that a paddle formed

from a blade and a shaft is used as the stirring element. The shaft is positioned so that its

axis is not more than 2 mm from the vertical axis of the vessel at any point and rotates

smoothly without significant wobble that could affect the results. The vertical centre line

of the blade passes through the axis of the shaft so that the bottom of the blade is flush

with the bottom of the shaft. The paddle conforms to the specifications shown in Figure

2. The distance of 25 ± 2 mm between the bottom of the blade and the inside bottom of

the vessel is maintained during the test. The metallic or suitably inert, rigid blade and

shaft comprise a single entity. A suitable two-part detachable design may be used

provided the assembly remains firmly engaged during the test. The paddle blade and

shaft may be coated with a suitable coating so as to make them inert. The dosage unit is

allowed to sink to the bottom of the vessel before rotation of the blade is started. A small,

loose piece of nonreactive material, such as not more than a few turns of wire helix, may

be attached to dosage units that would otherwise float. An alternative sinker device is

shown in Figure 3. Other validated sinker devices may be used.

21

Figure 3. Alternative sinker. Dimensions in millimeters.

Recommended procedure

Conventional-release (or immediate-release) dosage forms

Procedure. Place the stated volume of the dissolution medium (± 1%) in the vessel of the

specified apparatus. Assemble the apparatus, equilibrate the dissolution medium to 37 ±

0.5 °C, and remove the thermometer. The test may also be carried out with the

thermometer in place, provided it is shown that results equivalent to those obtained

without the thermometer are obtained. Place one dosage unit in the apparatus, taking care

to exclude air bubbles from the surface of the dosage unit. Operate the apparatus at the

specified rate. Within the time interval specified, or at each of the times stated, withdraw

a sample from a zone midway between the surface of the dissolution medium and the top

of the rotating basket or blade, not less than 1 cm from the vessel wall. Where multiple

sampling times are specified replace the samples withdrawn for analysis with equal

volumes of fresh dissolution medium at 37 °C or, where it can be shown that replacement

of the medium is not necessary, correct for the volume change in the calculation. Keep

the vessel covered for the duration of the test and verify the temperature (37 ± 0.5 °C) of

the medium at suitable times. Perform the analysis as directed in the individual

monograph using a suitable assay method. Test samples are filtered immediately upon

sampling using in-line filtration, unless filtration is demonstrated to be unnecessary. Use

an inert filter that does not cause adsorption of the active substance or contain extractable

substances that would interfere with the analysis. Centrifugation is not recommended

unless validated for the specific test. The test is to be conducted with six dosage form

units in parallel.

If automated equipment is used for sampling or the apparatus is otherwise modified,

verification is necessary that the modified apparatus will produce results equivalent to

those obtained with the apparatus described in this chapter.

Dissolution medium. A suitable dissolution medium is used. The volume specified refers

to measurements made between 20 °C and 25 °C. If the dissolution medium is a buffered

solution adjust the solution so that its pH is within 0.05 units of the specified pH.

Dissolved gases can cause bubbles to form, which may change the results of the test. In

such cases, dissolved gases must be removed prior to testing.

22

One appropriate method of deaeration is as follows: heat the medium, while stirring

gently, to about 41 °C, immediately filter under vacuum using a filter having a pore size

of 0.45 µm or less, with vigorous stirring and continue stirring under vacuum for at least

5 min, preferably 15 min, until no more bubbles are observed. Other validated deaeration

techniques for removal of dissolved gases may be used.

Time. Where a single time specification is given the test may be concluded in a shorter

period if the requirement for minimum amount dissolved is met. Samples are to be

withdrawn only at the stated times, within a tolerance of ± 2%.

Determine the quantity of active ingredient dissolved at the specified time(s) indicated in

the individual monograph. The result should be expressed as a percentage of the content

stated on the label of the dosage form.

Plot a graph % cumulative drug release Vs Time.

Student ID / Reg No


23

STANDARD GRAPH PROCEDURE of PARCETAMOL

Aim of this experiment: Prepare standard graph of parecetamol API by spectrophotometric method.

EXPERIMENTAL:

Materials: Paracetamol standard of was provided by Jazeera Pharmaceuticals

(P) Ltd. Analytical grade methanol and water.

Diluent Preparation: Methanol and Water (15:85, v/v) used as a diluents.

Standard Preparation: 10mg drug was dissolved in 15ml methanol and was

shaked well. Then 85ml water was added to it to adjust the volume upto

100ml (100ppm). From that 5ml was taken and volume was adjusted upto

50ml with diluents.

Table : 01 standard graph

10 mg in 100 ml

( 0.1mg/ml = 100 mcg/ml )

Concentrations

( mcg/ml )

Absorbance (nm)

2

4

6

8

10

12

14

16

18

20

Instrumentation: UV-Visible double beam spectrophotometer with matched

quartz cells (1cm), Model: Evolution 201, Make: Thermo Scientific, 81 Wyman

Street Waltham, Massachusetts, U.S Selection of Wavelength: Scan standard solution in UV spectrophotometer between 200 nm to 400 nm on spectrum mode, using diluents as a blank. Paracetamol shows λ max at 243 or ________ λ max _.

24

###############

Figure : 01 standard graph

25

Exp.No: Date:

DISSOLUTION TEST FOR PARACETAMOL TABLETS, WITH

DIFFERENT FORMULATIONS (U.S.P. 1995)

Conditions:

o Apparatus : II (paddle) o Medium : 900 ml of phosphate buffer pH 5 o Temp. : 37 ± 0.5

oC

o Speed : 50 rpm o Time : 45 min.

Procedure:

1. Place one tablet in the vessel, and then start the apparatus at the above

conditions.

2. At specified time intervals (5, 10, 15, 20, 25, 30, and 45 till 60 min) withdraw 1 ml

sample through a Millipore filtration unit (polyethylene tube with a cotton),

and place the sample in a test tube. Replace the withdrawn sample with 1 ml

fresh phosphate buffer kept at 37 ± 0.5 o

C.

3. Dilute 1 ml of the collected sample with fresh phosphate buffer (in a volumetric flask) ,

mix well.

4. Read the absorbance for the diluted samples at 249 nm against a blank of

phosphate buffer.

5. Calculate the concentration of paracetamol released and express this conc. As a

percentage of the labeled amount.

6. Plot the dissolution curve of paracetamol (% released vs.time).

USP stated that:

The tablet should release not less than 80% of its content within 30 minutes and not less

than 90% of its content within 45 minutes. (For immediate release tablets)

26

Observation of the dissolution for _________________________________ tablets:

Time

(min)

Absorbance

(nm)

Conc.

mcg/ml

Amount of drug dissolve

mg/ml

Cumulative amount of

drug dissolved in

900 ml

Cumulative % drug

dissolved

0

5

10

15

20

25

30

35

40

45

50

55

60

27

Plot the Time versus % release on graph paper and comment on the on the drug released rate?

Report : the % drug release for one hour was found to be __________________________.

28

Student ID / Reg No


Report:

###############

29

Exp.No: Date:

DISSOLUTION TEST FOR CIPROFLOXACIN Hcl TABLETS)

Conditions:

o Apparatus : I (basket) o Medium : 900 ml of distilled water o Temp. : 37 ± 0.5

oC

o Speed : 50 rpm o Time : 60 min.

Procedure:

Place one tablet in the basket, immerse in the vessel, and then start the

apparatus at the above conditions.

At specified time intervals (5, 10, 15, 20, 25, 30 and 45,50,55,60 min)

withdraw 1 ml sample from the dissolution medium, through a Millipore

filtration unit (polyethylene tube with a cotton), and place the sample in a test

tube.

Replace the withdrawn sample with 1 ml distilled water kept at 37 ±0.5o

C.

Dilute as per the requirement.

Read the absorbance for the diluted samples at 272 nm against a blank

distilled water.

Plot the dissolution curve (% released vs. time).

USP stated that: the tablet should release not less than 70% of its content within

30 minutes and not less than 90% of its content within 45 minutes

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STANDARD GRAPH OF CIPROFLOXACIN HCL

Abs (nm) Concentration (mcg/ml)

PLOT

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Observations of the dissolution of ciprofloxacin Hcl tablets: ( CIPRO BAY 500 MG )

Time

(min)

Absorbance

(nm)

Conc.

mcg/ml

Amount of drug dissolve

mg/ml

Cumulative amount of

drug dissolved in

900 ml

Cumulative % drug

dissolved

0

5

10

15

20

25

30

35

40

45

50

55

60

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Plot the Time versus % release on graph paper and comment on the on the drug released rate?

Report : the % drug release for one hour was found to be __________________________.

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Student ID / Reg No


Report:

###############

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Enhancement in solubility of poor water-soluble drugs by solid dispersion

Solid dispersion (SD) has been widely used to improve the dissolution rate,

solubility, and oral absorption of poor water-soluble drugs. SD refers to the group of solid

products consisting of at least two different components, generally a hydrophilic matrix and

a hydrophobic drug; the matrix can be either crystalline or amorphous. Solid dispersion was

first introduced to overcome the low bioavailability of lipophilic drugs by forming eutectic

mixture of drugs with water soluble carriers. Approximate 40% of new chemical entities

(NCE) being synthesized by combinatorial screening programs possessing superior

pharmacological activities are poorly soluble, which is a great obstacle in formulation

development.

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Exp.No: Date:

Preparation of Solid dispersion (SD) by physical mixture

Preparation by physical mixture

The physical mixture is prepared by using hydrophilic carrier in proportions viz., (--------).

Mixing of drug and carrier in a glass mortar. Solid mass is pulverized and passed through

sieve No. 120 to get uniform sized particles.

Observation

Procedure factor Name Grams

Total amount

Ratio

Polymer

Drug

Report : Solid dispersion (SD) of _____________ drug with ____________prepared by

physical mixture and submitted/ preserved for evaluation .

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Exp.No: Date:

Preparation of Solid dispersion (SD) by Solvent evaporation techniques

Solvent evaporation method

solid dispersions are prepared by solvent evaporation method using carrier PVP K 30 in

proportions viz., (-------). The drug and carrier are dissolved in methanol in a china dish and

the mixture is heated until the solvent evaporated and clear film of drug and carrier is

obtained. The resultant solid dispersion is scraped out with a spatula. Solid dispersions are

pulverized in a mortar and pestle and passed through a 125 µm sieve before packing in an

airtight container.

Observation

Procedure factor Name Grams

Total amount

Ratio

Polymer

Drug

Report : Solid dispersion (SD) of _____________ drug with ____________prepared by

physical mixture and submitted/ preserved for evaluation .

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Student ID / Reg No


Report:

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Exp.No: Date:

INFLUENCE OF VEHICLE ON THE SOLUBILITY OF CIPROFLOXACIN HCL

The study on solubility yields information about the structure and intermolecular forces of

drugs.

The term ‘solubility’ is defined as maximum amount of solute that can be dissolved in a

given amount of solvent. It can also be defined quantitatively as well as qualitatively.

Quantitatively it is defined as the concentration of the solute in a saturated solution at a

certain temperature. In qualitative terms, solubility may be defined as the spontaneous

interaction of two or more substances to form a homogenous molecular dispersion. A

saturated solution is one in which the solute is in equilibrium with the solvent. The solubility

of a drug is represented through various concentration expression such as parts, percentage,

molarity, molality, volume fraction, mole fraction.

Influence of Solvents

In the formulation, water or vegetable oils are normally used as solvents. The solubility of

the drug is due to the polarity of the solvent that is dipole movement. In addition, hydrogen

bonding between solute and solvent is essential. Therefore, structural features and presence

of nonpolar and polar groups in the molecule are important. Syrups and liquid oral solutions

are manufactured using water. The simple maxim of like-dissolve-like is the guiding

principle.

Procedure

Known concentration( 100 mg ) of drug ciprofloxacin Hcl is taken and dissolved in specified

vehicles and volume is make up to 100 ml with the same vehicle

Solute Solvent type

100 mg Ciprofloxacin Hcl

WATER

POLYETHYLENE GLYCOL 200

CASTOR OIL

Keep the prepared labeled bottle on mechanical shaker at constant room temperature 270 C

for 24 hr and analyze for the concentration spectrophotometrically at 272 nm and report the

order of solubility.

Report :

The order of solubility was found to be water > polyethylene glycol 200 > castor oil.

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Student ID / Reg No


Report:

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Exp.No: Date:

Demonstration of in-vitro diffusion study of Tran dermal drug delivery systems

Transdermal drug delivery system is defined as the topically administered medications in the

form of patches which when applied to the skin deliver the drug, through the skin at a

predetermined and controlled rate. Transdermal patches are delivered the drug through the

skin in controlled and predetermined manner in order to increase the therapeutic efficacy of

drug and reduced side effect

of drug.

Definition

A transdermal patch or skin patch is a medicatedadhesive patch that is placed on the skin to

deliver a specific dose of medication through the skin and into the bloodstream.

EVALUATION OF TRANSDERMAL PATCHES

Rolling ball test (Adhesive Test)

This test involves measurement of the distance that stainless steel ball travels along an

upward facing adhesive. The less tacky the adhesive, the further the ball will travel.

IN VITRO SKIN PERMEATION STUDIES

++++++++

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Hope you gain the knowledge about the course for any difficulty now or in future about

the course you can contact the supervisor at any time.

Wish you good luck

Best wishes for the upcoming exam

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COLLEGE OF PHARMACY DEPARTMENT OF ... OF PHARMACY DEPARTMENT OF PHARMACEUTICS LABORATORY MANUAL...

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