| الملخص | Abstract
This work has been carried out to develop national drug product contains miconazol nitrate (400 mg) as suppositories, is used for vaginal yeast infections .
Several formulations were prepared using different suppositories bases, preservatives. Selection of best formula relied solely on physicochemical testing of sample .
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 suppositories of good homogeneity, smoothness and hardness .
The expiry date calculated to be not less than (3) years.
Keywords:- Miconazol nitrate, Vaginal suppository, Stability study .
Introduction
Vulvovaginal candidiasis (VVC), sometimes referred to as candidal vaginitis, monilial infection, or vaginal yeast infection, is a common cause of vaginal irritation . It has been estimated that approximately (75 %) of all women will experience at least one episode of (VVC) during their lifetime. (VVC) is caused by an overabundance or overgrowth of yeast cells (primarily Candida albicans) that normally colonize in the vagina. Several factors are associated with increased rates of (VVC) in women, including pregnancy, uncontrolled diabetes mellitus, and the use of oral contraceptives or antibiotics. Other factors that may increase the incidence of (VVC) include the use of douches, perfumed feminine hygiene sprays, topical antimicrobial agents, and tight, poorly ventilated clothing and underwear. There is no direct evidence that (VVC) is transmitted by sexual intercourse [1] .
Miconazole is an imidazole antifungal used as miconazole base or nitrate in the treatment of superficial candidiasis, and of the skin infections dermatophytosis and pityriasis versicolor . It has also been given intravenously by infusion in the treatment of disseminated fungal infections, but other zoles are now[2] .
Miconazol nitrate Suppositories are indicated for the local treatment of vulvovaginal candidiasis (moniliasis) [3].
Miconazol nitrate works by weakening the cell membrane of the fungus, resulting in the death of the fungus. Miconazol nitrate vaginal suppository it used for vaginal yeast infections [4] .
Miconazol nitrate is a white or almost white powder, very slightly soluble in water, sparingly soluble in methanol, slightly soluble in ethanol (96 per cent) [5] .
Procedure:
Several formulations with different cream base were prepared and selected the best formula. The selected formula contains poly ethylene glycol 600 ( P.E.G), poly ethylene glycol 400 (P.E.G) ,preservative as inactive ingredients.
Pass the powder of miconazole nitrate through sieve (250 mic.) , in stainless steel mixer with jacket , transfer the stated amount of the following , fatty acid and preservative ,melt together at (50 ◦C) , dissolved with mixing for (15 min) , add miconazole nitrate (10 g) portion by portion to above mixture with continuous mixing for (20 min) , then homogenize for (10 min) , send the sample to quality control, when release transfer to the filling machine,pour into (2 g) mould plastic, pass through cooler,check the weight of suppositories, and should be comply with the limit of (B.P 2013),seal the plastic mould suppositories, by sealing machine.
Stability study :
Stability study was conducted on the product for (6) months at different temperatures ( room temperature , refrigerator , 30 ) ◦C to determine the expiration date and the best storage conditions.
Results and Discussion
A White to Creamy white torpedo shaped smooth suppository was obtained and the physico - chemical properties of it is presented in table (1) .On the other hand , stability studies is presented in tables (2) and (3).
In this study, different formulas of suppository were prepared according to the specification of British Pharmacopoeia 2013.
A White to Creamy white torpedo shaped smooth suppository of acceptable consistency was produced . The formula showed excellent stability at different temperatures (Ref. R.T, and 30, ) ◦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 miconazole nitrate (400 mg) with time at different temperatures.
Storage time (month) Temp.
◦C)) % of miconazole nitrate appearance
Zero time Room tempreture (R.T) 102.6 White to Creamy white torpedo shaped smooth suppository
1 Refrigerator
(Ref.) 102.6 = = =
R.T 102.27 = = =
30 101.83 = = =
2
Ref 102.38 = = =
R.T 101.94 = = =
30 101.05 = = =
3
Ref 102.16 = = =
R.T 101.61 = = =
30 100.27 = = =
4
Ref 101.78 = = =
R.T 101.26 = = =
30 99.49 = = =
5
Ref 101 = = =
R.T 100.28 = = =
30 98.51 = = =
6
Ref 100.56 = = =
R.T 99.63 = = =
30 97.64 = = =
Table -2-The stability of Miconazole nitrate suppositopry (400 mg) , concentration of Miconazole nitrate at zero time =102.6 % of the label amount
30◦C % Concentration at ◦C % Concentration at R.T Concentration at Ref. % Time /day
101.83 102.27 102.6 30
101.05 101.94 102.38 60
100.27 101.61 102.16 90
99.47 101.26 101.78 120
98.51 100.28 101 150
97.64 99.63 100.56 180
Regarding the expiry date of the prepared formula we followed the Zero - order rate of reaction that is expected for kinetic of Miconazole nitrate suppository particularly in the first stage of reduction of concentration.
T90%=0.1C/K
Where:
C=concentration at zero time
K= rate of reaction
T= time
Table -3- The (90%) at different temperature.
T90%Year T90%day Temp.
4 1460 R.T◦C
3.5 1277 Ref.◦C
3 1095 30◦C
References
1- Onlinefrom, http://www.digitalnaturopath.com/cond/C443001.html,
vaginitis/vaginal infection
2- Sean C Sweetman, 2010, printed by LEGO S.P.A., Martindale 36 the complete Drug Reference, Pharmaceutical Press, USA.
3-Onlinefrom,http://www.medicineonline.com /drugs/m/2305/MONISTAT-3-miconazole-nitrate-200-mg-Vaginal-Suppositories.html.
4- Onlinefrom, http://www.drugs.com/cdi/miconazole-suppositories.html
5- British Pharmacopoeia press, 2013, British Pharmacopoeia, U.K.
6- Kim Huynh,(2009),Accelerating aging, Handbook of stability testing in pharmaceutical development,springer ,USA . | en_US |
