تصييغ السميثيكون 40 ملغم /مل كقطرة فموية

Abstract

Abstract The present work has been carried out to develop pharmaceutical product contains (40mg/ml) simethicone as an oral drop. The drop it is used as an antiflatulent in infants and children.Different batches have been prepared including different oral drop bases and preservatives.Selection for better combination relied solely on physical and chemical testing of samples. Stability study was conducted on the product for(6) months at different temperatures (25,40,50,60) °C to determine the expiration date and the best storage conditions. From this study we obtained oral drops suspension as an antiflatulent, of good homogeneity. The expiry date calculated to be not less than (2) years From the date of production.

Keywords: simethicone, flatulence., oral drop.

Introduction Simethicone is dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane. It is used as an adjunct in the symptomatic treatment of flatulence, functional gastric bloating, and postoperative gas pains. For self-medication, the drug is used as an antiflatulent to relieve symptoms commonly referred to as gas, including upper bloating, pressure, fullness, or stuffed feeling. Simethicone also has been used prior to gastroscopy to enhance visualization and prior to radiography of the intestine to reduce gas shadows. Although there is gastroscopic evidence that simethicone aids in the elimination of gas from the GI tract, the relationship of gas accumulation to what patients commonly refer to as symptoms of gas under ordinary conditions is not clear; however, the drug also has been shown to be effective in relieving these symptoms. Preparations of simethicone with antacids, antispasmodics, or digestive enzymes are available.The clinical use of simethicone is based on its antifoam properties. Silicone antifoams spread on the surface of aqueous liquids, forming a film of low surface tension and thus causing collapse of foam bubbles. Simethicone reportedly allows mucus-surrounded gas bubbles in the GI tract to coalesce and be expelled.[1]. Simethicone has been used for treating the symptoms of infant colic.[2] Simethicone is a clear, colorless liquid of various viscosities, practically insoluble in water, very slightly soluble or practically insoluble in anhydrous ethanol, miscible with ethyl acetate, with methyl ethyl ketone and with toluene .[3]. The formula of simethicone oral drop contains simethicone (40 mg /ml) as an active ingredient and also contains sodium saccharin, sodium citrate, citric acid ,glycerin, propylene glycol, methyl paraben, propyle paraben, peach flavor,sorbitol, ethanol (96%) and deionized water as inactive ingredients. Table -1- list of ingredients

Item No. Constituents Quantity / 100 ml 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Simethicone Citric acid Sodium citrate Methyl paraben Propyle paraben Sodium saccharin Glycerin Propylene glycol Sorbitol Ethanol (96%) Peach flavor Distilled water 4 gm 2 gm 3 gm 0.2 gm 0.02 gm 4 gm 10 gm 10 gm 20 gm 5 ml 0.01 gm add to 100 ml

Experimental work In suitable Pyrex beaker transfer sodium citrate, citric acid, methyl paraben, propyle paraben, ethanol (96%) and distilled water, the solution heated up to (60)◦c for (15 minutes) with stirrer, in another suitable beaker transfer the following material: glycerin, propylene glycol, sorbitol ,sodium saccharin, peach flavor simethicone and distilled water, mix for(10 minutes) , mix all beakers with homogenous for (15) minutes, check the pH; it should be between (3.5 – 4.6 ),fill in (30) ml amber glass bottle.

Stability study Stability study was conducted on the product for (6)months at different temperatures(25,40,50,60)◦C to determine the expiration date and the best storage conditions.

Results and Discussion The result of stability study showed that the simethicone oral drop product has good stability. In this study, different formulas were prepared according to the specification of United state pharmacopeia (30).The product showed a good stability (physically and chemically stable) at different temperature (25, 40, 50, and 60) °C. According to this study, the expiration date has been estimated to be not less than( 2 ) years from the date of manufacturing at room temperature.

Table -1-The physical and chemical changes of simethicone oral drop (40 mg/ml) within time at different temperatures.

Storage time (month) Temp. °C % content of simethicone pH appearance Zero time R.T 99.48 4.5 white homogenous suspension

1 25 99.45 4.5 white homogenous suspension 40 98.79 4.5 white homogenous suspension 50 98.21 4.5 white homogenous suspension 60 98.15 4.5 white homogenous suspension

2 25 99.40 4.5 white homogenous suspension 40 98.53 4.5 white homogenous suspension 50 98.21 4.5 white homogenous suspension 60 98.1 4.5 white homogenous suspension 3

RT 99.35 4.5 white homogenous suspension 40 98.3 4.5 white homogenous suspension 50 98.09 4.5 white homogenous suspension 60 97.9 4.5 white homogenous suspension 4

25 99.32 4.5 white homogenous suspension 40 98 4.5 white homogenous suspension 50 98.01 4.5 white homogenous suspension 60 97.8 4.5 white homogenous suspension 5

25 99.25 4.5 white homogenous suspension 40 97.8 4.5 white homogenous suspension 50 97.16 4.5 white homogenous suspension 60 96.6 4.5 white homogenous suspension 6

25 99.2 4.5 white homogenous suspension 40 97.65 4.5 white homogenous suspension 50 96.21 4.5 white homogenous suspension 60 96.1 4.5 white homogenous suspension

Table - 2 -The stability of simethicone oral drop , concentration of simethicone at zero time =99.48 of the label amount

60 °C 50 °C 40 °C Concentration at 25°C Time /day 98.15 98.21 99.79 99.45 30 98.1 98.21 98.53 99.40 60 97.9 98.09 98.3 99.35 90 97.8 98.01 98 99.32 120 96.6 97.16 97.8 99.25 150 96.1 96.21 97.65 99.2 180

The 90% at different temperature. Table -3- T90% Year T90% day Temp. °C 3 1095 25 2.3 839 40 1.8 657 50 1.5 547 60

References: 1- American Society of Health System Pharmacists; AHFS Drug Information (2009). Bethesda, M.D. , p. 2975. 2- Novak, K.M. (ed.)(2008). Drug Facts and Comparisons Edition. Wolters Kluwer Health. St. Louis, Missouri , p. 1757. 3- British Pharmacopoeia press, (2013), British Pharmacopoeia, U.K. 4 - United states Pharmacopoeia press,( 2010), U.S.P 30, U.S.A.

الخلاصة : نفذ هذا العمل لتطوير منتج صيدلاني يحتوي على (40 ملغم / مل) سيميثيكون كقطرة فم. يتم استخدام القطرة كمضاد لغازات البطن في الرضع والأطفال. حضرت عدة تركيبات باستخدام قواعد قطرات فم مختلفة والمواد الحافظة. اختيرت أفضل تركيبة بالاعتماد على الاختبارات الفيزياوية والكيمياوية للعينات. أجريت دراسة الاستقرار على المنتج لمدة (6) أشهر في درجات حرارة مختلفة ( 40,25 ,60,50 ) م° لتحديد تاريخ انتهاء الصلاحية وأفضل ظروف التخزين. من هذه الدراسة حصلنا على قطرات فم معلقة كمضاد للفيروسات، جيدة التجانس. تاريخ انتهاء الصلاحية محسوب على أن لا يقل عن سنتان من تاريخ الانتاج.