-11تركيبة صيدلانية عراقية لمستحضرهيدروكسيد الالمنيوم الجاف 225ملغم /5مل , هيدروكسيد المغنسيوم 200 ملغم /5 مل وسميثكون 25ملغم /5مل معلق فموي لعلاج عسر الهضم ، الحرقة، وانتفاخ البطن مع دراسة ثباتيتها.

Abstract

Abstract This work has been carried out to develop national drug product contains dried aluminum hydroxide (225 mg) , magnesium hydroxide (200 mg) and simethicon (25mg / 5ml) as oral suspension is used to treat dyspepsia, heartburn, flatulence .Several formulations were prepared using different suspensions bases , preservatives and suspending agent. 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 an antiviral suspension of good homogeneity. The expiry date calculated to be not less than (3) years.

Keywords:- dried aluminum hydroxide , magnesium hydroxide, simethicone , anti acid, antigas , dyspepsia, heartburn, flatulence

Introduction This medication is used to treat the symptoms of high stomach acid such as stomach upset, heartburn, and acid indigestion. It is also used to relieve symptoms of extra gas such as belching, bloating, and feelings of pressure / discomfort in the stomach/gut. Simethicone helps break up gas bubbles in the gut. Aluminum and magnesium antacids work quickly to lower the acid in the stomach. Liquid antacids usually work faster/better than tablets or capsules. This medication works only on existing acid in the stomach. It does not prevent acid production. It may be used alone or with other medications that lower acid production (e.g., H2 blockers such as cimetidine / ranitidine and proton pump inhibitors such as omeprazole [1] . The combination of aluminum hydroxide , magnesium hydroxide, and simethicone is used to treat heartburn, acid indigestion, upset stomach, and bloating caused by gas [2]. Dried aluminium hydroxide is white or almost white, amorphous powder, practically insoluble in water, It dissolves in dilute mineral acids and in solutions of alkali hydroxides. Magnesium hydroxide is white or almost white, fine, amorphous powder, practically insoluble in water, it dissolves in dilute acids, Simethicone clear, colorless liquid of various viscosities, practically immiscible in water, very slightly miscible or practically immiscible in anhydrous ethanol, miscible with ethyl acetate, with methyl ethyl ketone and with toluene [3]. Aluminum hydroxide , magnesium hydroxide and simethicon oral suspension is a generic drug isnot manufactured in Iraqi factories ; therefore, the aim of this study is a necessity to have an Iraqi formula for this dosage form with its stability study compatible with specifications of united state pharmacopeia. This study is considered one of the important documents for the purposes of registration in the ministry of health. The formula contains dried gel aluminum hydroxide (225 mg/5ml) (Antacid), magnesium hydroxide (200mg / 5ml) (Antacid), simethicone (25mg / 5ml) (Antigas) as active ingredient.

Materials and methods Several formulations with different oral suspension base were prepared and selected the best formula. The selected formula contains methyl paraben, propyl paraben , sorbitol , limon flavor , saccharin sodium , xanthan gum , citic acid , sodium citrate , peppermint flavor and distilled water as inactive ingredient. In suitable beaker transfer distilled water , heat to boil , then dissolve respectively the following ,methyl paraben and Propyle paraben, then cool to room temperature.In another beakers triturate avicel with distilled water ,triturate xanthan gum with distilled water, mix together all mixtures, then add respectively the following with continuous mixing for (15 min), sorbitol, dried Aluminum hydroxide, magnesium hydroxide, simethicone, citric acid dissolved in distilled water, sodium citrate dissolved in distilled water, lemon flavor, peppermint flavor. complete the volume with distilled water, check the pH; it should be between (5.5 - 8) , 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 In this study, different formulas of suspension were prepared according to the specification of British pharmacopeia 2013. A white homogenous suspension of acceptable consistency was produced and the physicochemical also our formula showed excellent stability at different temperatures (R.T, 40, 50, and 60) ◦C. The results of stability study for selected formula presented in tables (1),(2). 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 physical – chemical changes of aluminum hydroxide ,magnesium hydroxide and simethicone oral suspension [4]. Storage time (month) Temp. (°C) % of aluminum hydroxide % of magnesium hydroxide % of simethicone appearance Zero time R.T 107.27 101.81 100 White homogenous suspension

1 R.T 107.27 101.81 100 40 107.06 101.6 99.79 = 50 107.04 101.58 99.77 = 60 106.96 99.23 99.69 =

2 R.T 107.17 101.71 99.9 = 40 106.96 101.5 99.69 = 50 106.94 101.48 99.67 = 60 106.86 101.4 99.8 = 3

R.T 107.07 101.61 99.59 = 40 106.86 101.4 99.38 = 50 106.84 101.38 99.36 = 60 106.76 101.3 99.28 = 4

R.T 106.97 101.51 99.49 = 40 106.76 101.3 99.28 = 50 106.74 101.28 99.26 = 60 106.66 101.2 99.18 = 5

R.T 106.87 101.41 99.39 = 40 106.66 101.2 99.18 = 50 106.64 101.18 99.16 = 60 106.56 101.1 99.08 = 6

R.T 106.77 101.31 99.29 = 40 106.56 101.1 99.08 = 50 106.54 101.08 99.06 = 60 106.46 101 98.98 =

Regarding the expiry date of the prepared formula we followed the Zero - order rate of reaction that is expected for kinetic of dried aluminum hydroxide , magnesium hydroxide and simethicone oral suspension particularly in the first stage of reduction of concentration. T90%=0.1C/K Where: C=concentration at zero tim K= rate of reaction T= time The expiry date calculated of dried aluminum hydroxide , magnesium hydroxide and simethicon oral suspension presented in table (2) .

Table -2 - The (T 90 %) of aluminum hydroxide ,magnesium hydroxide and simethicone oral suspension at different temperature. Temp.(°C) T90% year of Al(OH)2 T%90 day of Al(OH)2 T90% year of Mg(OH)2 T90% day of Mg(OH)2 T 90 % year of Simethicone T 90 % day of Simethicone R.T°C 4 1460 3.5 1277 3.4 1241 40 °C 3.5 1277 3.3 1204 3.2 1168 50 °C 3 1095 2.9 1058 2.9 1058 60 °C 2 730 2.5 912 2.5 912

References 1- online from , http://www.webmd.com/drugs/2/drug-56561/antacid-ii-plus-simethicone-oral/details 2- online from , http://www.emedicinehealth.com/drug- aluminum_hydroxide_magnesium_hydroxide_and_simethicone/article_em.htm, September 3, 2015. 3- British Pharmacopoeia press, 2013, British Pharmacopoeia, U.K. 4- Kim Huynh,(2009),Accelerating aging, Handbook of stability testing in