formulation and evaluation of trihexyphenidyl …. rpa131400251014.pdf · 2018. 7. 1. ·...

301 | P a g e International Standard Serial Number (ISSN): 2319-8141

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International Journal of Universal Pharmacy and Bio Sciences 2(6): November-December 2013

INTERNATIONAL JOURNAL OF UNIVERSAL

PHARMACY AND BIO SCIENCES IMPACT FACTOR 1.89***

ICV 5.13*** Pharmaceutical Sciences RESEARCH ARTICLE……!!!

FORMULATION AND EVALUATION OF TRIHEXYPHENIDYL

HYDROCHLORIDE TABLTES

Rajesh Akki1*

, P V Ayodhya Neelima1, N Vijaya lakshmi

1, K Manasa

1,

Munagala Gayatri Ramya2

1Hindu College of Pharmacy, Amaravathi Road, Guntur-522 002

2University College of Pharmaceutical Sciences, Acharya Nagarjuna University,

Nagarjuna Nagar, Guntur-522 510.

KEYWORDS:

Trihexyphenidyl,

optimization and process

parameters, Preformulation

studies.

For Correspondence:

Rajesh Akki *

Address:

Department Of

Pharmaceutics, Hindu

College of Pharmacy,

Guntur-522 002.

ABSTRACT

The study was undertaken with an aim to formulate antiparkinson agent

on oral drug delivery. The selected antiparkinson agent was

Trihexyphenidyl hydrochloride. The active pharmaceutical ingredient of

Trihexyphenidyl hydrochloride was selected and formulated as

immediate release of oral conventional tablets of 2mg.Preformulation

studies were carried and the results were found to be satisfactory.

Experimental started with the process variables such as Bulk density,

Angle of repose, and Compressibility index of the API. The compatible

excipients were selected for formulation development. The content

uniformity, Assay, and dissolution profile of Trihexyphenidyl

formulation was compared with the Innovator’s product. Binder

variation study, disintigrant variation study and lubricant variation study

was performed..However further formulation development involves

optimization and process parameters. In present work direct

compression were employed to prepare tablets. Microcrystalline

cellulose and Pharmatose DCL21 is used as diluents. Pregelatinised

starch, corn starch and sodium starch glycolate are selected as

disintegrants. Tablets are compressed using 8mm flat punches with

Rimek mini press II, a 12 station rotary compression machine. Post

compression parameters hardness, friability, weight variation,

disintegration time, wetting time, content uniformity and dissolution

studies are studied. The developed trails were tested for in-vitro

dissolution profile and compared with the reference product of

trihexyphenidyl-2 from Watson laboratories.

- 302 - | P a g e International Standard Serial Number (ISSN): 2319-8141


INTRODUCTION:

Trihexyphenidyl (Artane, Apo-Trihex, Parkin, Pacitane), also known as benzhexol, is

an antiparkinsonian agent of the antimuscarinic class. It has been in clinical usage for decades. The

drug is available as the hydrochloride salt. Trihexyphenidyl is used for the symptomatic treatment

of Parkinson's disease in mono- and combination therapy. It is active in postencephalitic,

arteriosclerotic, and idiopathic forms. The drug is also commonly used to treat extrapyramidal side

effects occurring during antipsychotic treatment. It reduces the frequency and duration of oculogyric

crises as well as of dyskinetic movements and spastic contractions. Excessive salivation may also

respond. Trihexyphenidyl may improve psychotic depression and mental inertia frequently

associated with Parkinson's disease and symptomatic problems caused by antipsychotic treatment.

The drug cannot cure Parkinson's disease, but may provide substantial alleviation of symptoms. An

estimated 50 to 75% of patients with Parkinson's disease will react positively and experience a 20 to

30% symptomatic improvement. To increase therapeutic activity trihexyphenidyl is often given

concomitantly with levodopa, other antimuscarinic or antihistaminic (e.g. diphenhydramine) agents.

Combination treatment with dopaminergic agonists such as cabergoline is also possible. This is

often termed a 'multidimensional approach'.It has also been prescribed for Essential Tremors.

Direct compression method is selected upon several trails at last formula was optimized. During

development of formula in process tests such as LOD, Bulk density, Tapped density,

Compressibility index and Hausner’s ratio were evaluated for granules and weight variation,

hardness, thickness, disintegration were evaluated for the core tablets. Finished products were

evaluated for Disintegration, content uniformity Assay, Related substances and

dissolution.Trihexyphenidyl hydrochloride was selected and formulated as immediate release of oral

conventional tablets of 2mg.The objective of the present study is as follows:-

Preformulation Studies, Formulation of Oral conventional tablet of Trihexyphenidyl hydrochloride

by Wet Granulation and Direct Compression method. Evaluation of tablets for their Physical

parameters, Drug Content, Disintegrating time, Assay, content uniformity and Dissolution Rate.

Selection of formulation based on the Evaluation. Evaluation of Marketed formulation. Comparison

of optimized formulation and Marketed formulation.

MATERIALS AND METHODS:

Trihexyphenidyl hydrochloride was a gift sample from Natco pharma, Hyderabad. All other

chemicals and excepients were purchased from Local Market.

Table: 1 PREFORMULATION STUDIES OF DRUG

S.no. Angle of

repose (θ)

Compressibility

Index (%)

Hausner’s ratio

Bulk

density

Tap

density

1 43 38 1.47 0.52 0.30

http://en.wikipedia.org/wiki/Antiparkinsonian

http://en.wikipedia.org/wiki/Antimuscarinic

http://en.wikipedia.org/wiki/Parkinson%27s_disease

http://en.wikipedia.org/wiki/Extrapyramidal_symptoms

http://en.wikipedia.org/wiki/Antipsychotic

http://en.wikipedia.org/wiki/Oculogyric_crisis



http://en.wikipedia.org/wiki/Levodopa

http://en.wikipedia.org/wiki/Diphenhydramine

http://en.wikipedia.org/wiki/Cabergoline



TABLE: 2 SOLUBILITY STUDIES

.% of Solubility

Time

intervals

(min)

pH4.5aceate buffer pH 6.8 phophate buffer 0.1N HCl Water

Average Average average Average

15 102.2 97.5 89.3 103.1

30 105.4 100.5 92.6 104.4

45 102.7 98.8 89.3 102.2

60 106.0 98.5 90.3 101.0

90 100.5 96.3 82 100.5

Drug-Excipient Compatibility studies

Drug is in intimate contact with one or more excipients in all the dosage forms. Later it could affect

the stability of drug. Knowledge of drug-excipients interaction is useful in selecting an appropriate

excipient. Drug and excipients are stored at 55° for 14 days, 40°C at RH 75% for 14days, 28 days.

After 14, 28 days they are subjected for analysis of description, assay, LOD, purity.

TABLE 3: DRUG EXCIPIENT COMPATIBILITY

TEMPERATURE AND HUMDITY 550 40

0 + 75% RH

DAYS 0TH

14TH

7TH

14TH

28TH

S.No

Excipients Ratio Description

Initial Final

1 API 1 BLD BLD

2 MCC (pH 101) 1 BLD BLD

3 MCC (pH 102) 1 BLD BLD

4 Povidone USP(PVPK-30) 1 BLD BLD

5 HPMC E5 1 BLD BLD

6 Corn starch 1 BLD BLD

7 Pre gelatinised starch 1 BLD BLD

8 Sodium starch glycolate 1 BLD BLD

9 Magnesium stearate 1 BLD BLD

10 Stearic acid 1 BLD BLD

11 Colloidal silicon dioxide 1 BLD BLD

12 API + Avicel(ph101) 1:10 BLD BLD

13 API + Avicel(ph102) 1:10 BLD BLD

14 API + Povidone usp(k-30) 1:5 BLD BLD

15 API + HPMC E5 1:5 BLD BLD

16 API + Cornstarch 1:5 BLD BLD

17 API + SSG 1:5 BLD BLD

18 API + PGS 1:5 BLD BLD

19 API + Magnesium stearate 1:0.5 BLD BLD

20 API + Stearic acid 1:0.5 BLD BLD

21 API + colloidal silicon

dioxide

1:0.5 BLD BLD

BLD – Below limit of detectable



Preparation of tablets using direct compression method

Table:4 Formulations:

S.No Ingredients F1 F2 F3 F4 F5 F6 F7

1 THP 2 2 2 2 2 2 2

2 Pharmatose DCL21 49 46

3 Avicel pH 102 90 89.5 137.5 137.5 137.5 137.5 137.5

4 Corn starch 5.416

5 Pre gelatinized starch 7.5

6 Sodium Starch Glycolate 5 9 9 9.0 9.0 9.0

7 Aerosil 0.75 0.832

8 Magnesium Stearate 0.75 1.25 1.5 1.5 1.5 1.5 1.5

Total 150 150 150 150 150 150 150

S.No Ingredients F8 F9 F10 F11 F12 F13 F14

1 Trihexy phenidyl hydro chloride 2 2 2 2 2 2 2

2 Avicel ph 102 140.5 134.5 138.25 136.75 137.5 137.5 137.5

3 sodium starch glycolate 6.0 12 9.0 9.0 9.0 9.0 9.0

4 Magnesium stearate 1.5 1.5 0.15 2.25 1.5 1.5 1.5

Total 150 150 150 150 150 150 150

TABLE 5: DIRECT COMPRESSION BATCH PROCEDURES:

S.No

Step1 Weigh and

Mix ingredients

After passing

through 40# mesh

Step2 Addition

of ingredients to

blend

After passing

through 40#

mesh

Dry mix blending

time

And instrument used

for blending

Addition of

lubricants

To the dry mix

which is already

passed through

mesh

Lubricati

on

Blending

time

F1

API+DCL

21+Avicel PH

102+PGS

--------- 10 min

Aerosil +

Magnesium stearate

40#

2 min

F2

API+DCL

21+Avicel PH 102

+ corn

starch+SSG

---------- 10 min

Aerosil +

Magnesium stearate

40#

2 min

F3 API+Avicel PH

102+SSG --------- 10 min

Magnesium stearate

40# 2 min

F4

Avicel PH 102 +

SSG

(Mix for 10 min)

API

Double cone blender

,15 min

Magnesium stearate

60# 3 min



F5

Avicel PH 102 +

SSG

(Mix for 10 min)

API Double cone blender

15 min

Magnesium stearate

60# 3 min

F6 API+Avicel PH

102 + SSG -------

Double cone blender

15 min

Magnesium stearate

60# 5 min

F7 API+Avicel PH

102 + SSG ---------

Double cone blender

10,15,20

min(10+5+5min)

Magnesium stearate

60# 5 min

F8 API+Avicel PH

102 + SSG -------- Double cone blender

10 MIN

Magnesium stearate

60# 5 min

F9

API+Avicel PH


10 MIN

Magnesium stearate

60# 5 min

F10 API+Avicel PH


10 MIN

Magnesium stearate

60# 5 min

F11

API+Avicel PH

102 + SSG --------- Double cone blender

10 MIN

Magnesium stearate

60# 5 min

F12 API+Avicel PH

102 + SSG -------- Conta bin blender

18,20,22

Magnesium stearate

40#

2,3,5

min

(2+1+2)

F13 API+Avicel PH

102 + SSG --------

Conta bin blender

16,18,20 min

(16+2+2)

Magnesium stearate

40# 2 min

F14 API+Avicel PH

102 + SSG ------- Conta bin blender

18,20,22

Magnesium stearate

40# 2,3 min

In all the above formulations geometrical mixing was done

TABLE 6: PHYSICAL PROPERTIES OF TABLETS

Formulations Average

weight(mg)

Thickness

(mm)

Hardness

kps

Disintegration

(sec)

Friability

(%)

F1 149 2.54 5.95 55 0.09

F2 151 2.42 5.5 55 0.00

F3 151 2.38 5.2 30 0.03

F4 155 2.39 9.7 24 0.07

F5 155 2.69 5.0 5 0.06

F6 153 2.54 6.6 7 0.00

F7 151.5 2.4 6.0 21 0.00

F8 154.7 2.65 4.6 5 0.00

F9 153.4 2.54 5.3 7 0.00

F10 153.5 2.82 4.37 5 0.00

F11 153 2.7 3.74 5.5 0.01

F12 151.8 2.50 6.27 7 0.03

F13 150.2 2.7 4.5 4.5 0.17

F14 151 3.1 6.3 6 0.0015



TABLE: 7 EFFECT OF HARDNESS USING F5 FORMULATION

EVALUATION OF TABLETS

Breakability test in tablets:

To define the procedure for Breakability test for Trihexyphenidyl HCl 2&5 mg. Breakability test is

applied on tablets with single or multiple score lines, to find out the influence of breakability

methodology on uniformity of weight. The test is applied to confirm that the subdivided parts of a

tablet comply with the requirements for uniformity of weight.

Acceptance criteria: Not more than two of the individual weights, out of 20 tablets, deviate

from the average weight by ± 10 % and none deviate by ± 20.0%.

MOISTURE PICK UP STUDIES

To carry out moisture pick up studies or hygroscopic studies of API, blend, finished product.

TABLE: 8 MOISTURE PICK UP STUDIES

25°C

Temp/Humidity

Observation

after 168 hours (API)

Lubricated

Blend Core tablets

29% RH

Description

Off White color

powder

Off white

powder.

White colored round

shaped tablets

debossed with ‘N’ and

‘ T’ on either side of

score line and ‘2’ on

lower side..

% Moisture

pick up

(maximum)

NIL

0.0069%

NIL

43% RH

Description complies complies complies

% Moisture

pick up

(maximum)

NIL NIL NIL

75%RH

Description complies complies complies

% Moisture

pick up

(maximum)

0.0135% 0.06% 0.0681%

Different hardness

F5

Average weight

mg

Thickness

(mm)

Hardness

kps

Disintegration

(sec)

Friability

(%)

3 150.2 3 2.7 3.5 0.03

3-5 151.5 2.35 4.5 5 0.07

5-8 154.7 2.69 4.92 5 0.06

8-10 154.2 2.36 9.9 7 0.00



Table : 9 DISSOLUTION PROFILE AT DIFFERENT HARDNESS

FIGURE: 2 EFFECT OF HARDNESS

Table 10 Dissolution profile Results from F1 to F7

Sampling

Time

Percentage of drug release

F1 F2 F3 F4 F5 F6 F7

0 0 0 0 0 0 0 0

10 92 93 94.5 95.4 99 90.9 97.5

20 92.8 94 95.3 97.5 99.4 91.6 98

30 93 94 96.6 98.1 98.4 92.4 98.6

45 94.7 95 97 98.7 98.4 92.68 99.2

0

20

40

60

80

100

120

0 10 20 30 40 50

% O

F D

RU

G R

ELEA

SE

TIME IN MIN

EFFECT OF HARDNESS

3

3 to 5

5 to 8

8 to 10

Time(min) % Drug release at different

Hardness

3kps 3-5kps 5-8kps 8-10kps

0 0 0 0 0

10 96.1% 95.4 99 95.8

20 98.1% 96 99.4 96.1

30 99.7 97 98.4 97

45 99.8 97.8 98.4 98.7



TABLE 11: DISSOLUTION PROFILE RESULTS FROM F8 TO F14

Sampling

Time

Percentage Of Drug Release

F8 F9 F10 F11 F12 F13 F14

0 0 0 0 0 0 0 0

10 100 97.9 97.3 96 92.9 97.6 99

20 100.7 98.2 101 96.4 95 100.2 100.3

30 101 98.6 99.4 96 94.9 100.3 100.5

45 103 97.4 98.8 97.4 95.5 100.4 100.5

Figure: 3 PERCENTAGE DRUG RELEASE F1 TO F5


0

20

40

60

80

100

120

0 10 20 30 40 50

% D

RU

G R

ELEA

SED

TIME

% DRUG RELEASED

F1

F2

F3

F4

F5

0

20

40

60

80

100

120

0 10 20 30 40 50

% O

F D

RU

G R

ELEA

SED

TIME

% DRUG RELEASED

F6

F7

F8

F9

F10




Table 12: Results of Content Uniformity and Assay

0

20

40

60

80

100

120

0 10 20 30 40 50

% O

F D

RU

G R

ELEA

SED

TIME

% DRUG RELEASED

F11

F12

F13

F14

Formulations

Content uniformity

of blend 10 samples Blend

Assay C.U of tablets Assay of tablets

minimum Maximum

F1 92.4 94.4 91.9 92.5 90.4

F2 94 96.5 92.5 93.2 94.5

F3 95 97.9 94.4 96.4 95.4

F4 97.8 106.8 106.9 98.8 109.2

F5 98.4 100 100.6 98.2 99.1

F6 80.9 134.1 101.8 98.5 100

F7 98 100.9 103.2 99.5 98.9

F8 100 103.2 101 101.2 105.1

F9 100.4 105.7 103.3 99.8 103.4

F10 99 102.4 104.3 100.1 103.5

F11 98.4 101.2 103.5 99.5 102.4

F12 94.2 116.4 100.2 96.7 94.5

F13 99.9 108.6 103.3 98.3 96.8

F14 98.4 106.6 100.6 101.1 100.8



Table 13: STABILITY DATA

S.No CHARACTERISTICS

TESTED INITIAL I

st MONTH II

nd MONTH III

rd MONTH

1 Description

White colored round

shaped tablets

debossed with ‘N’

and ‘ T’ on either

side of score line

and ‘2’ on lower

side.

Complies Complies Complies

2 Average Weight (in mg) 150.0 mg 154.0 153.2 152.1

3 Water content (%w/w) 5.5 5.8 5.9%

4 Dissolution (By HPLC) 102.5% 102.4 102.6% 103.6

5 Assay (By HPLC) 101.3% 102.3 % 99.7% 99.86

6 Related substances

Unknown impurity-Total 0.995 0.990 0.900

Unknown impurity-Max 0.960 0.900 0.900

TABLE: 14 PERCENTAGE OF DRUG RELEASE (STABILITY DATA)

Sampling Time Percentage Of Drug Release

30 days 60 days 90 days

0 0 0 0

10 100 100.6 101

20 100.6 101 101.3

30 101.5 101.6 102

45 102.4 102.6 103.6

Figure: 6 PERCENTAGE DRUG RELEASE

0

20

40

60

80

100

120

0 10 20 30 40 50

% O

F D

RU

G R

ELEA

SE

TIME IN MIN

STABILITY DATA

Percentage Of Drug Release 30 days





Table 15: Breakability test

S.No T.w(mg) R1 L1

1 151 70 81

2 152 73 78

3 155 76 79

4 151 76 75

5 152 71 81

6 155 70 85

7 152 76 75

8 152 75 77

9 154 78 76

10 150 75 74

11 155 86 69

12 153 79 73

13 152 77 75

14 152 82 70

15 152 75 77

16 151 74 77

17 154 83 71

18 152 71 81

19 153 87 65

20 154 72 82

Min 70 65

Max 87 85

Avg 76.3 76.05

T.W: Total Weight, R1: Right side half tablet, L1: Left side Half tablet. Not more than two of the

individual weights, out of 20 tablets, deviate from the average weight by ± 10 % and none deviates

by ± 20%.so here breakability test is passed.

Table 16: Blending time optimization dry mix based on Content uniformity

F12 F13

18MIN 20MIN 22MIN 16MIN 18MIN 20MIN

97.2 100.3 60.9 99.2 103.1 91.8

96.6 74.8 76.7 94.1 102.4 112.5

98 75 73 102.2 99.9 102.5

99 56.8 69.4 102.9 103.5 79.8

100.7 92.2 25.3 92.4 102.4 122.7

98.2 100.2 80.5 93.6 101.1 99.5

96.6 60.2 55.8 118.7 108.6 93.5

99.8 65 88.3 101.1 103.2 105.6

94.2 75.7 58.8 102.8 103.5 106.3

116.4 95.1 44.2 94.9 104.4 103.9

Avg 99.67 79.53 63.29 100.2 102.7 101.8



Table 17: BLENDING TIME OPTIMIZATION OF BLEND AFTER LUBRICATION

BASED ON CONTENT UNIFORMITY

F 12 F13

2MIN 3MIN 5MIN 2min

97.3 98.8 98.8 99.7

100.1 98.5 97.7 100.6

99.4 100.2 96.1 100.6

98 99.7 95.8 96.8

98 96.8 96.2 102.9

99 96.8 98.6 121.1

100.5 97.7 97.8 99.8

100.8 97.4 96.9 86.3

103.2 98 101.6 99

99.6 98.5 103.9 101.8

Avg 107.5 98.24 98.34 100.9

INNOVATOR DETAILS

Trihexyphenidyl Hydrochloride Tablets, USP 2 mg are 10/32", scored, round, white, flat faced,

tablets imprinted DAN DAN and 5335 supplied in bottles of 100 and 1000. Dispense in a tight

container with child-resistant closure.Store at 20°-25°C (68°- 77°F). WatsonLaboratoriesInc.

Corona, CA 92880 USA

Table : 18

LOTNUMBER L6E0619

Hardness Thickness Weight

content

Disintegration time

Moisture

4.5-5.6 kps 2..5 mm 180 mg 36-40 sec 3.6%

Figure: 7 Percentage Drug Release Of Comparing With Innovator Product

0

50

100

150

0 10 20 30 40 50%O

F D

RU

G R

ELEA

SED

TIME

% DRUG RELEASED

INNOVATOR

F14



TABLE:19 PERCENTAGE DRUG RELEASE OF INNOVATOR SAMPLE AND F14

Time %Drug release

Innovator F14

0 0 0

10 100 99

20 100.5 100.3

30 101 100.5

45 102.9 100.5

RESULTS AND DISCUSSION

The present investigation was undertaken to formulate Trihexy phenydyl hydrochloride used for the

treatment of Parkinson’s disease.Direct compression techniques were used in formulating the drug

into oral conventional tablet. As per the above data solubility is more in pH 4.5 buffers is better than

the other pH 6.8 buffer and water, 0.1NHCL. Drug excipient compatability all are in below the

limit. All the experimental formulation batches have been subjected to various evaluations.viz,

average weight, friability, disintegration, thickness, hardness, dissolution, content uniformity.F1 to F

14 were carried out by Direct Compression method.In formulation F1 Pharmatose DCL

concentrations is decreased to 32.66%; MCC concentration is increased to 60% and Pregelatinised

starch 5% is used for 150mg tablet. DT was found to be 55 seconds; % drug release 94.7%. Assay

and content uniformity are not achieved.In formulation F2 Pregelatinised starch is replaced with

SSG 3.33% and Corn starch 3.61% is used. Content uniformity and assay values are not achieved.In

formulation F3, Pharmatose DCL and Corn starch are removed. Increased the concentration of

Avicel PH102 to 91.66%; SSG 6% is used. DT was found to be 30 seconds, % drug release is 97%.

Content uniformity and assay results are better than previous formulation.In formulation F4 method

of preparation changes. Blending is done at 2 stages with geometrical mixing.. (i) Avicel PH 102 +

SSG for 10minutes. (ii) API for 15 minutes.Content uniformity and assay are better. But dissolution

does not match with the innovator. Formulation F5 was conducted to study the effect of hardness.

There is no effect of hardness on DT and dissolution. Formulation F6 was carried out with new API.

Blending time is 15 minutes. %drug release is 92.68%. Content uniformity and assay results failed.

Formulation F7 was carried out to check the content uniformity by changing the blending time 10,

15, 20 minutes. At 10 and 15 minutes content uniformity and assay achieve better results.

FORMULATION F8 TO F11 WAS CARRIED OUT TO STUDY THE EFFECT OF

EXCIPIENTS.

Formulation F8 was done to study the effect of 4% SSG. Here the result shows that there is no effect

on DT and Dissolution. Formulation F9 was done to study the effect of 8% SSG. Here the result

shows that there is no effect on DT and Dissolution. Formulation F10 was done to study the effect of



0.5% magnesium stearate. Here the result shows that there is no effect on DT and Dissolution.

Formulation F11 was done to study the effect of 1.5% magnesium stearate. Here the result shows

that there is no effect on DT and Dissolution.

BLENDING TIME OPTIMIZATION BEFORE AND AFTER LUBRICATION F12 TO F13

In formulation F12, batch size was increased, so occupancy of blend also increases, this may show

effect on content uniformity. In this case blending time is studied at 18, 20, 22 minutes. After

lubrication 2, 3, 5 minutes blending is done. For 18 minutes, results are good.

Formulation F13 was carried out to check and optimize the parameters. Here blending time is

studied at 16, 18, 20 minutes. For 18 minutes results are good. So 18 min blending time is

optimized.

OPTIMIZED FORMULA

In formulation F14 blending are done for 18 minutes. Content uniformity and assay results are good.

% drug release matches with innovator. All parameters match with innovator.

This is the optimized formulation.

CONCLUSION

The active pharmaceutical ingredient of Trihexyphenidyl hydrochloride was selected and formulated

as immediate release of oral conventional tablets of 2mg.Preformulation studies were carried and the

results were found to be satisfactory. The compatible excipients were selected for formulation

development. The oral route of drug administration is the most important method of administering

drugs for systemic effects. The content uniformity, Assay, and dissolution profile of

Trihexyphenidyl formulation was compared with the Innovator’s product. Binder variation study,

disintigrant variation study and lubricant variation study was performed. However further

formulation development involves optimization and process parameters.Post compression

parameters hardness, friability, weight variation, disintegration time, wetting time, content

uniformity and dissolution studies are studied. Tablets containing pregelatinised starch, corn starch

showed disintegration time which are not satisfactory than the tablets containing sodium starch

glycolate. Micro crystalline cellulose PH 102 used in direct compression since it is free flowing

powder. Content uniformity, Assay, disintegration time and percentage drug release of optimized

formulation F-13 and F-14 are mostly matched with marketed product.

Direct compression method is selected upon several trails at last formula was optimized. Finished

products were evaluated for Disintegration, content uniformity Assay, Related substances and

dissolution. The developed trails were tested for in-vitro dissolution profile and compared with the

reference product of trihexyphenidyl-2 from Watson laboratories. The in-vitro dissolution of

formula F14 was nearest to the reference product. In direct compression method, different



formulation were carried out for the selection of excipients, change in concentration of excipients,

method of preparation changing, changing of blending time, study on effect of hardness, effect of

disintegrant , lubricant and blending time.

Blending time optimization plays a major role to achieve content uniformity and Assay. At different

intervals of time blending was conducted and at last optimized the blending time based on the

content uniformity and assay. Impact of hardness against dissolution was performed and optimum

hardness was derived. Impact of disintegrating agent sodium starch glycolate against dissolution was

performed and optimum concentration of disintegrating agent was achieved. Impact of lubricant

against dissolution was performed and optimum concentration of lubricant was achieved. Moisture

pick up studies were performed for API, Lubricated blend, Core tablets to know the hygroscopic

characters. All the results were found to be satisfactory. The optimized batch was performed

stability studies at 40°C±2°C /75%±5%RH for three months. Stability samples were evaluated

initially, after one month, second month and third month. The results were compared with the

predetermined specifications. All the results were found to be satisfactory. Hence the designed and

developed formula of Trihexyphenidyl hydrochloride tablets was stable.

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1. Lachman L., Liberman H. and Kanig J.; The Theory and Practice of Industrial Pharmacy;

Third Edition: 293-345, 346-373.

2. Aulton M.; Pharmaceutics: The Science of Dosage Form Design; International Student

Edition: 304-321, 347-668.

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