| الملخص | Abstract
This work has been carried out to develop national drug product contains (200mg / 5ml) sodium valproate as an oral solution, it is used for the treatment of epilepsy in adults and children.
Several formulations were prepared using different syrup bases and preservatives. Selection of best formula relied solely on physico-chemical testing .
Stability study was conducted on the product for (6) months at different temperatures to determine the expiration date and the best storage conditions.
From the study we obtained syrup colorless and good clarity.
The expiry date calculated to be not less than (3) years.
Keywords:- Sodium valproate, epilepsy, oral solution.
Introduction
Epilepsy is a chronic medical disorder or condition, usually resulting in unpredictable, unprovoked recurrent seizures that affect a variety of mental and physical functions. It is one of the most common neurological diseases, affecting more than (3 million) people in the U.S. and about (50 million) people worldwide. Epilepsy was one of the first brain disorders to be described. It was mentioned in ancient Babylon more than (3.000) years ago.Through the ages, the strange behavior caused by some seizures has led to the creation of numerous superstitions and prejudices [1].
People with epilepsy are prone to having periods of uncontrolled electrical activity in the brain, which may lead to seizures. Sodium valproate helps to control electrical activity in the brain. This reduces the chances of having seizures[2].
Sodium valproate which belongs to a group of medicines known as anticonvulsants, it is a white or almost white, crystalline, hygroscopic powder , very soluble in water, freely soluble in ethanol (96 per cent) [3].
Sodium valproate syrup contains sodium valproate (200mg / 5ml) as an active ingredient and it is a generic drug that is not manufactured in the Iraqi factories. Therefore, the aim of study is to prepare an Iraqi formula for this dosage form with its stability study that is to be compatible with specifications of British pharmacopeia. This study is necessity and it's considered to be one of the important documents for the purposes of registration in the Iraqi ministry of health.
Materials and methods
Several formulations with different cream base were prepared and selected the best formula. The selected formula contains suger, sodium saccharin, methyl paraben, propyl paraben, almond flavor, sorbitol (70 %) , glycerin and distilled water as an inactive ingredients.
In suitable beaker transfer distilled water,heat at (70 °C) in water bath then dissolve the following materials ,methyl paraben , propyle paraben , sodium saccharin, cool to (45 °C) , then add sorbitol (70 %) , glycerin , sodium valproate ,almond flavor,with contiuous mixing for (15 min),check the (pH), it should be between (6.5 - 8),complete the volume with distilled water then mix for (30 min),fill in amber glass bottle.
Stability study :
Stability study was conducted on the product for (6) months at different temperatures (room temperature,40,50 and 60) ◦C to determine the expiration date and the best storage conditions.
Results and Discussion
A white homogenous cream was obtained and the physicochemical properties of it is presented in table (1) .The results of stability studies is presented in tables (2) and (3).
In this study, different formulas of syrup were prepared according to the specification of united state Pharmacopoeia 2013.
A Clear colorless syrup of acceptable consistency was produced and the physicochemical also our formula showed excellent stability at different temperatures (R.T, 40, 50, and 60) ◦C.
According to this study, the expiration date has been estimated to be not less than (3) years from the date of manufacturing at room temperature.
Table -1-The physico – chemical changes of sodium valporate (200mg / 5ml) with time at different temperatures.
Storage time (month) Temp.
◦C)) % of sodium valproate pH
(6.5 - 8) appearance
Zero time R.T 102.24 7.88 Clear colorless syrup
1 RT 102.14 7.88 = = =
40 102.00 7.78 = = =
50 101.78 7.76 = = =
60 101.48 7.74 = = =
2
RT 102.04 7.78 = = =
40 101.9 7.76 = = =
50 101.68 7.74 = = =
60 101.38 7.72 = = =
3
RT 101.94 7.68 = = =
40 101.8 7.66 = = =
50 101.65 7.65 = = =
60 101.27 7.63 = = =
4
RT 101.83 7.66 = = =
40 101.63 7.64 Clear to faint yellow syrup
50 101.39 7.62 = = =
60 101.04 7.60 = = =
5
RT 101.63 7.60 Clear colorless syrup
40 101.4 7.57 Clear to faint yellow syrup
50 101.1 7.55 = = =
60 100.71 7.52 = = =
6
RT 101.43 7.55 Clear colorless syrup
40 101.2 7.52 Clear to faint yellow syrup
50 100.87 7.48 = = =
60 100.54 7.44 = = =
Table - 2 -The stability of sodium valporate solution (200mg / 5ml), concentration of sodium valporate at zero time =102.24% of the label amoun
Conc.at (60 ◦C) % Conc.at (50 ◦C) % Conc.at (40 ◦C) % Concentration at (R.T) % Time / day
101.48 101.78 102 102.14 30
101.38 101.68 101.9 102.04 60
101.27 101.65 101.8 101.94 90
101.04 101.34 101.63 101.83 120
100.71 101.1 101.4 101.63 150
100.54 100.87 101.2 101.43 180
Regarding the expiry date of the prepared formula we followed the Zero – order rate of reaction that is expected for kinetic of sodium valporate solution particularly in the first stage of reduction of concentration.
T95%=0.1C/K
Where:
C=concentration at zero time
K= rate of reaction
T= time
Table -3- The (95 %) at different temperature.
T95%Year T95%day Temp.
4 1460 R.T◦C
3.5 1277.5 40◦C
3 1095 50◦C
2.5 912.5 60◦C
References
1- Marvin M. Goldenberg, Overview of Drugs Used For Epilepsy and Seizures, P T. 2010 Jul; 35(7): 392–415.
2- onlinefrom,http://medguides.medicines.org.uk/nhs/medicine.aspx?
name=Sodium+Valproate&use=Epilepsy&preparation=4
3- British Pharmacopoeia press, 2013, British Pharmacopoeia, U.K.
4- Sean C Sweetman, 2011, printed by LEGO S.P.A., Martindale 37 the complete Drug Reference, Pharmaceutical Press, USA.
5- Janet Woodcock, 2012, P.D.R 66 physicians’ desk reference,USA.
6- Kim Huynh,(2009),Accelerating aging, Handbook of stability testing in pharmaceutical development,springer ,USA . | en_US |
