A STUDY OF STABILITY AND COMPATIBILITY OF EXTEMPORANEOUS PRODUCTS (LINCTUS SIMPLEX PEADIATRIC) IN MANUFACTURING DEPARTMENT AT GENERAL HOSPITAL MELAKA

BY: MOHD ASHRAF BIN MOHD YUSOFF AMMAR ASIF BIN ABDUL AZIZ SUHAIL BIN SHARIR
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Extemporaneous preparations
Made facilitate to take drugs especially paediatrics and elderly who cannot swallow pills or tablets.

Provide the dosage strength that rarely used by patient.

To fulfil the demand the manufacturer department of Hospital Melaka prepared drugs as extemporaneous to be supplied for the patient at all district hospital, country clinic and for general hospital.

Problems of Extemporaneous Preparation

Not achieve the desired compatibility and stability. Reports from others hospital shows that the preparation expired faster than its due date.

For Example, the Linctus Simplex has a lifespan about 6 months, but according to feedback from other hospitals and clinics the products only stand about 2 months because of discolorations and precipitations in the preparation made.

Linctus Simplex
Due to discoloration of the Linctus Simplex patient become less confident to use the product. This will cause many Linctus Simplex had been thrown and wastage happen. Pharmacist from manufacturing department had conducted a test to determine the exact life shelf of the Linctus Simplex and the more effective storage condition. The objective of the research is to determine the exact shelf-life of this product furthermore promote a new expiry date of this product.

Linctus Simplex ( contine )

After the exact expiry dates of this product have been known, the pharmacy manufacturing department can estimate actual production that needs to be done and further avoid wastage. This research also aim for study the more effective ways of storage to Hospital and other clinics for keeping it shelf life longer

AIM OF THE STUDY

The aim of this study is to determine the shelf life of extemporaneous compounding of Linctus Simplex in General Hospital Melaka.

OBJECTIVES OF THE STUDY

To determine the stability and compatibility of the Linctus Simplex in Manufacturing Department, General Hospital Malacca.

To ensure the quality of extemporaneous products.

To determine that in use shelf life applied to the product is not appropriate and should be reconsidered.
To able to suggest the suitable shelf life and storage of the product.

Method
Study Design Involves direct observation of sample Linctus Simplex taken from Manufacturing Department of General Hospital Melaka from 1 March 2011 until 5 July 2011.

Method
15 samples of Linctus Simplex that freshly prepared is taken randomly for the pharmacy manufacturing department and was placed at 5 different places. The places are the manufacturing store, refrigerator, cold room, out-patient pharmacy and a regular room. The manufacturing store temperature is below 25 Celsius, the refrigerator temperature is about 2-4 Celsius, the cold room temperature is around 4-8 Celsius and the normal room temperature ranged for 23-32 Celsius. The observation is done every week by comparing with the newest batch of the simplexes.
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SAMPLE SELECTION
The entire sample was taken from batch 110301, 110308, and 110315 and then repacked with the standard 60ml plastic bottle to 5 bottles. The data is collected everyweek by comparing it with the newest batch.

Inclusion Factors
Linctus Simplexes are prepared for the usage in hospital Melaka ONLY. Production of Linctus Simplex batch 110301, 110308, and 110315.

Exclusion Factors
Linctus simplex that prepared for other hospitals (Alor Gajah Hospital, Peringgit District clinic)

RESULTS & DISCUSSION

Type Of Sample Linctus Simplex Paediatric 60 ml Linctus Simplex Paediatric 60 ml Linctus Simplex Paediatric 60 ml Group Number Of Sample 1 Duration of sample observation 1 March 21 June 2011 8 March-28 June 2011 Batch Number Type of test to be evaluated Observation Density Of colour / Colour change Observation Density Of colour / Colour change Observation Density Of colour / Colour change

110301

110308

15 March-5 July 2011

110315

Table of group of samples, dates of preparation and batches number of preparations.

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Group Sample 1 ( 1 March 21 June 2011)

Week Of Observation Out Patient Department (25 celcius and above)
NC
NC NC NC NC NC NC NC NC CC CC

Pharmacy Store (16 Celcius Below)

NC
NC NC NC NC NC NC NC NC NC NC

Refrigator (Below 8 Celcius)

Normal Cold Room Room Temperature temperature (manufacture Room) (28 Celcius (18-25 Celcius) and above)
NC
NC NC NC NC NC CC CC CC CC CC

1
2 3 4 5 6 7 8 9 10 11

NC
NC NC NC NC NC NC NC NC NC NC

NC
NC NC NC NC NC NC NC NC NC CC

12
13 14 15 16

CC
CC CC CC CC

CC
CC CC CC CC

NC
NC CC CC CC

CC
CC CC CC TC

CC
CC CC CC CC

Table of observation group sample 1(batch 110301)

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Sample 1
Place Room Temperature
Out Patient Department

Weeks 7
10

Cold Room Temperature Pharmacy Store Refrigerator

11 12 14

Table of duration taken by sample 1 to change colour concentration

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Group of Sample 2 ( Start 1 Week Behind Sample 1)

Week Of Observation Out Patient Departme nt (25 celcius and above) Pharmacy Store (16 Celcius Below) Refrigator (Below 8 Celcius) Normal Room temperatur e (28 Celcius and above) Cold Room Temperature (manufacture Room) (18-25 Celcius)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

NC NC NC NC NC NC NC NC NC CC CC CC CC CC CC CC

NC NC NC NC NC NC NC NC NC NC CC CC CC CC CC CC

NC NC NC NC NC NC NC NC NC NC NC NC NC NC CC CC

NC NC NC NC NC NC NC CC CC CC CC CC CC CC CC CC

NC NC NC NC NC NC NC NC NC NC CC CC CC CC CC CC

Table of observation group sample 2(batch 110308)

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Sample 2

Place Room Temperature Out Patient Department Cold Room Temperature Pharmacy Store

Weeks 8 10 11 11

Refrigerator

15
14

Table of duration taken by sample 2 to change colour concentration

Group of Sample 3 ( Start 2 Week behind Sample 1)

Week Of Observation Out Patient Department (25 celcius and above) Pharmacy Store (16 Celsius Below) Refrigerator (Below 8 Celsius) Normal Room temperatur e (28 Celcius and above) NC NC NC NC NC NC NC CC CC CC CC CC CC CC CC CC Cold Room Temperature (manufacture Room) (18-25 Celcius)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

NC NC NC NC NC NC NC NC NC CC CC CC CC CC CC CC

NC NC NC NC NC NC NC NC NC NC NC CC CC CC CC CC

NC NC NC NC NC NC NC NC NC NC NC NC NC CC CC CC

NC NC NC NC NC NC NC NC NC CC CC CC CC CC CC CC

Table of observation group sample 3 (batch 110315)

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Sample 3
Place Room Temperature Out Patient Department Cold Room Temperature Pharmacy Store Refrigerator Weeks 8 10 10 12 14

Table of duration taken by sample 3 to change colour concentration

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The time (week) taken by group of sample to change colour at different places

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DISCUSSION
16 14 12 10 8 Lowest Average

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4 2 0 Room Temperature Out Patient Department Cold Room Temperature Pharmacy Store Refrigator

Highest

The highest, average and lowest time (week) taken by group of sample to change colour at different places

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DISCUSSION
The average time needed for samples in room temperature to change colour was 7.6 weeks.
Samples in outpatient department was 10 weeks, follow by cold room temperature which is 10.3 weeks. The average time of samples in pharmacy store to change colour was 10.7. Samples place in refrigerator had higher average time to change colour which was 14.3 weeks.

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Main factor which affects the stability of the samples

Temperature - storage condition for the product also play the important part in stability of the product, the high temperature tend to degrade the product stability faster than lower temperature. Light exposure; samples which were places in room that had more exposure to the light tend to degrade in stability compare to the room that had lower exposure to the light.
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Main factor which affects the stability of the samples

The original formulary use amaranth as a colouring agent -has been banned in the United States by the FDA as it is a suspected carcinogen. Carmoisine used as colouring agent replacement for amaranth, this change can be the reason for instability of the product in term of colour. The recommendation is by using other type of colouring agent than carmoisine and amaranth that more reliable and stable to improve the stability of the product.
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Main factor which affects the stability of the samples

Syrup were made by manufacturing department extemporaneously. Recommendation - using the syrup that were produce from the company that specialize in pharmaceutical preparation

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Conclusion
The factors reduce the stability and comatibility of Linctus Simplex are temperatures, light exposure, colouring agent, and quality of syrup use to prepare the product. Recommended shell life for Linctus Simplex for Paediatric is two months if store in cold room temperature that between 18 and 25 degree Celsius that had low amount of exposure from light especially from sun light.

In order to improve the stability of the product, we recommended this product is store in refrigerator and use amber plastic container.
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