Field of invention

The present invention relates to the preperation of pharmaceutical compositions comprising calcium carbonate, magnesium carbonat and simeticone powder DC in the treatment of acid indigestion, heartbum, uncomfortable bloating, flatulence and painful trapped wind, having an improved manufacturing process by using direct compression method.

Background of the invention

Calcium carbonate is an inorganic salt used as gastric antacid, widely used in pharmaceutical industry and its chemical structure is shown in the Figure I. It is also used for dietary supplement. Calcium carbonate has molecular weight of 100.087 g/mol, is a odorless, a fine white powder with chalky taste.

Calcium carbonate is a dietary supplement, needed by the body for healthy bones, muscles, nervous system, and heart. Also, it is generally used as an antacid to relieve heartbum, acid indigestion, and upset stomach, individually.

Figure 1

Magnesium carbonate is an inorganic salt used as an over the counter antacid in pharmaceutical industry and its chemical structure is shown in the Figure 2. Magnesium carbonate has molecular weight of 84.314 g/mol, is a odorless and white solid.

Magnesium carbonate, also known as magnesite, is a mineral supplement used to prevent and treat low amounts of magnesium in the blood. It is also used for heartburn and upset stomach caused by overproduction of acid in the stomach such as stomach upset, heartburn, and acid indigestion. Magnesium is very critical for the normal functioning of human body; nerves, cells, muscles, bones, and the heart.

Figure 2 Simethicone has a chemical name as 3,3,5,5-tetramethyl-2,4-dioxa-3,5-disilahexane; silanedione and its chemical structure is shown in the Figure 3. Simethicone has molecular weight of 238.461 g/mol, is gray, translucent and viscous liquid.

Simethicone is a mixture of polydimethylsiloxane and hydrated silica gel. It is mainly used to relieve the symptoms of excessive gas in the gastrointestinal tract such as namely bloating, burping and flatulence. Another medical use is to treat colic in babies.

Figure 3

Simeticone has been used for decades in the treatment of gastrointestinal disorders such as flatulence, dyspepsia and infant colics. Simeticone is safe and effective up to 500mg oral administration in the treatment of symptoms caused by gases according to an FDA expert. Beside this, a monograph is published about use of simeticone for the symptomatic treatment of excessive gas formation and gas accumulation in the intestinal tract by the German Federal Institute for Drugs and Medical Devices. Simeticone is effective and safe for adults, pregnant women and infants according to tested and verified in a number of clinical studies.

Combination of Calcium carbonate, Magnesium carbonate and Simeticone powder DC is used for the effective relief of acid indigestion, heartburn, uncomfortable bloating, flatulence and painful trapped wind.

Acid indigestion is also known as heartburn, Acid reflux, or pyrosis. Acid reflux is a common condition that affects many people. It happens when some of the acidic stomach contents go back up into the esophagus, travelling up towards the throat. The condition effects throat and oesophagus become flooded from the acid produced by the stomach, causing a burning feeling.

Bloating is a feeling when your belly feels swollen after eating. The reason is generally caused by excess gas production or disturbances in the movement of the muscles of the digestive system. Bloating can often cause pain, discomfort feeling and also It can make human stomach bigger.

Trapped wind is relevant to producing gas in human body. Gas is created during digestion. It is natural to producing gas while food digestion. In some situations, gas gets stuck in human bowels and facing a problem in gas transfer. The problem is that human body creates a lot of gas. If human body can’t release this gas, it remains trapped in the abdomen, causing sharp pain, cramping, swelling, tightness, and even bloating. Some foods are more likely to cause excess gas production that results in trapped wind. Some of them: dairy products of cow’s milk, cheese and yoghurts, high fibre foods such as beans and lentils, onions and garlic, fruits containing high levels of fructose, like strawberries, pineapples and bananas, fizzy drinks and alcohol. Beside this; eating too much or too quickly and chewing gums are the possible reason of trapped wind.

Rennie deflatine is a trademark of Bayer, this products includes active ingredients of calcium carbonate, magnesium carbonate and simethicone. It is used for the effective relief of acid indigestion, heartbum, uncomfortable bloating, flatulence and painful trapped wind. Rennie deflatine composition: Sorbitol (E420), Talc, Pregelatinised maize starch, Potato starch, Magnesium stearate, Mint flavour Lemon flavour except three active ingredients.

WO 1996/010409 relates to a pharmaceutical composition comprises calcium carbonate and simethicone. The invention relates to a liquid antacid composition for neutralizing stomach acid comprising: an alkaline earth carbonate salt; and alkali metal phosphate salt; an alkali metal bicarbonate salt; other exipients, and simethicone.

EP3124048 relates to a pharmaceutical composition comprises sodium alginate, calcium carbonate, sodium bicarbonate, digestive enzyme (eg actinidin) and liquorice (Glycyrrhiza glaba), useful for treating gastroesophageal reflux.

WO 1995/001784 relates to a pharmaceutical combination comprising famotidine, sucralfate and an antiflatulent such as simethicone, useful for treating flatulence, indigestion, gastric ulcer and gastro-oesophageal reflex.

Summary of the invention

The present invention relates to the preparation of pharmaceutical compositions comprising Calcium Carbonate, Magnesium Carbonate and Simeticone powder DC for use in the treatment acid indigestion, heartbum, uncomfortable bloating, flatulence and painful trapped wind, having an improved manufacturing process by using direct compression method.

The present invention relates to a pharmaceutical chewable tablet composition comprising Calcium Carbonate, Magnesium Carbonate and Simeticone powder DC, wherein the weight ratio of Simeticone powder DC to total tablet weight is between 1:40 to 1:66 (w/w) and the tablet composition is prepared by direct compression method.

Detailed description of the invention

The present invention relates to the preparation of pharmaceutical compositions comprising Calcium Carbonate, Magnesium Carbonate and Simeticone powder DC, having an improved manufacturing process by using direct compression method.

The present invention relates to the preparation of chewable tablet compositions comprising Calcium Carbonate, Magnesium Carbonate and Simeticone powder DC for use in the treatment acid indigestion, heartbum, uncomfortable bloating, flatulence and painful trapped wind, wherein process including direct compression method.

The present invention relates to a pharmaceutical chewable tablet compositions comprising Calcium Carbonate, Magnesium Carbonate and Simeticone powder DC, wherein the weight ratio of Simeticone powder DC to total tablet weight is between 1:40 to 1:66 (w/w) and the tablet composition is prepared by direct compression method.

Calcium and magnesium are necessary for many systems in human body. Calcium and magnesium are used as antacids to relieve heartburn, acid indigestion, and upset stomach.

Simethicone are used as anti-gas that allows gas bubbles in the stomach and intestines, which allows for easier passage of gas.

Calcium carbonate, magnesium hydroxide, and simethicone is a combination antacid, anti-gas medicine used to treat heartburn, indigestion, gas and bloating, or stomach discomfort caused by overeating.

Tablet is a pharmaceutical oral dosage form (Oral Solid Dosage, or OSD) or solid unit dosage form. Tablets are defined as the solid unit dosage form of medicament or medicaments with suitable excipients.

Chewable tablets are one of the member of oral dosage forms intended to be chewed and then swallowed by the patient rather than swallowed whole. Chewable tablets should be designed to be palatable and be easily chewed and swallowed.

The major formulation factors on development chewable tablets are flow, lubrication, disintegration, organoleptic properties, compressibility, compatibility and stability. Also, critical factors on developing chewable tablets are taste and flavours, aroma, mouth-feel properties.

The powder form of simeticone is particularly chosen in formulation development for the chewable tablet dosage form including Calcium Carbonate, Magnesium Carbonate and Simeticone.

Liquid form of simeticone has negative properties for an optimum formulation development process. The risk of sticking problem is high when liquid form of simeticone is used in formulation development for the chewable tablet.

When using liquid form of simethicone, a longer process design is required for formulation development procedure and indirectly production procedure.

The present invention relates to a pharmaceutical chewable tablet compositions comprising Calcium Carbonate, Magnesium Carbonate and Simeticone powder DC, wherein the weight ratio of Simeticone powder DC to total tablet weight is between 1:40 to 1:66 (w/w) and the tablet composition is prepared by direct compression method.

The present invention relates to a pharmaceutical chewable tablet compositions comprising Calcium Carbonate, Magnesium Carbonate and Simeticone powder DC, wherein the weight ratio of Simeticone powder DC to total tablet weight is between 1:40 to 1:66 (w/w), more preferably 1:54 (w/w) and the tablet composition is prepared by direct compression method.

Direct compression is the process in which tablets are compressed directly from the powder blends of the active ingredient and the minimum excipients are needed (a diluent (filler-binder), a disintegrant and a lubricant).

Depending on flow and compactability of the compression properties of final blend; a diluent (filler-binder), a disintegrant and a lubricant are used in direct compression method, in generally.

In this invention, the term "simeticone powder DC" means herein as an active ingredient or materials that have same physical properties according to content of substance for simethicone and silica-amorphous.

"Simethicone powder DC" term is used herein for a powder comprising simethicone 40%-80% by weight and amorphous-silica 20%-50% by weight.

Preferably, "Simethicone powder DC" is a powder comprising Simeticone 50% by weight and Silica-amorphous 50% by weight.

Preferably, "Simethicone powder DC" is a powder comprising Simeticone 60% by weight and Silica-amorphous 40% by weight.

Preferably, "Simethicone powder DC" is a powder comprising Simeticone 70% by weight and Silica-amorphous 30% by weight.

Preferably, "Simethicone powder DC" is a powder comprising Simeticone 80% by weight and Silica-amorphous 20% by weight.

The present invention relates to a pharmaceutical compositions comprising 680mg Calcium Carbonate, 80mg Magnesium Carbonate and 25mg Simeticone powder DC as active ingredients.

The present invention relates to a pharmaceutical compositions comprising different amounts of active ingredients by (w/w) except the pharmaceutical composition comprising 680mg Calcium Carbonate, 80mg Magnesium Carbonate and 25mg Simeticone powder DC as active ingredients. In the present invention, the expression "composition” is used to indicate a pharmaceutical composition or a medical device composition or a supplement composition or a food composition.

The present invention relates to the preparation of pharmaceutical compositions comprising active ingredients and excipients, wherein process including in direct compression method.

In another embodiment, the pharmaceutical composition further comprises at least one excipient selected from a diluent, a sweetener, a glidant, a lubricant and an aroma.

The present invention provides a pharmaceutical composition for use in the treatment acid indigestion, heartbum, uncomfortable bloating, flatulence and painful trapped wind in a patient in need thereof.

In this invention, the composition comprising Calcium Carbonate, Magnesium Carbonate and Simeticone powder DC can be used for in the treatment acid indigestion, heartbum, uncomfortable bloating, flatulence and painful trapped wind.

Advantages

Multiple unit operations can be avoided by using simeticone powder form.

The sticking problem is minimalized by using Simeticone powder DC form in this pharmaceutical composition.

In any of the embodiments described herein, direct compression method of manufacturing process can be used according to API’s physical and chemical properties. Excipients can be selected according to environment of process.

Direct compression formulations can be developed with minimal numbers of excipients.

In any of the embodiments described herein, direct compression method of manufacturing process is an economical process. It provides reduced processing time, reduced costs, fewer manufacturing steps, and less number of equipments are required.

The present invention provides pharmaceutical composition comprising Calcium Carbonate, Magnesium Carbonate and Simeticone powder DC and relevant excipients, characterized by i) A simple and exclusive manufacturing process ii) Stable and useful formulation.

The term "treatment" means any treatment of a disease or condition in a subject, such as a mammal, including:

1) preventing or protecting against the disease or condition, that is, causing the clinical symptoms not to develop;

2) inhibiting the disease or condition, that is, arresting or suppressing the development of clinical symptoms; and/or 3) relieving the disease or condition that is, causing the regression of clinical symptoms.

Diluents can be selected from the group, but are not limited to, calcium hydrogen phosphate calcium carbonate, calcium phosphate, calcium sulphate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, maltodextrin, mannitol, microcrystalline cellulose, potassium chloride, powdered cellulose, pregelatinised starch, sodium chloride, sorbitol, starch, sucrose, sugar spheres, talc, tribasic calcium phosphate, and xylitol or mixture thereof. A preferred diluent is Pregelatinised Starch.

Sweeteners can be selected from the group, but are not limited to, mannitol, glycerol, acesulfame potassium, aspartame, cyclamate, isomalt, isomaltitol, saccharin and its sodium, potassium and calcium salts, sucralose, sorbitol, alitame, thaumatin, glycyrrhizin, neohesperidine dihydrochalcone, steviol glycosides, neotame, aspartame-acesulfame salt, maltitol, maltitol syrup, lactitol, x litol, erythritol. A preferred sweetener is sorbitol.

Glidants can be selected from the group, but are not limited to, colloidal silicon dioxide, colloidal silica, cornstarch, talc, calcium silicate, magnesium silicate, magnesium trisilicate, amorphous silica, colloidal silicon, silicon hydrogel, powdered cellulose, silicon dioxide, talc, tribasic calcium phosphate and other materials known to one of ordinary skill in the art. The preferred glidant is talc.

Lubricants according to the present invention include, but are not limited to, calcium stearate, magnesium stearate, mineral oil, stearic acid, fumaric acid, sodium stearylfumarate, zinc stearate and polyethylene glycol. The preferred lubricant is magnesium stearate.

Aroma can be selected from the group, but not limited to, lemon aroma, mint aroma, other fruit aromas and mixtures thereof. The preferred aroma is lemon aroma and/or mint aroma.

Example 1: Chewable Tablet composition comprising calcium carbonate, magnesium carbonate, simeticone powder DC . Stage 1 Sieving and Mixing

Sieving and mixing: Magnesium Carbonate, Simeticone powder DC, Pregelatinised Starch, Sorbitol, Lemon Aroma and Mint Aroma. . Stage 2 Sieving and Mixing

Sieving and mixing: Calcium Carbonate, Talc and Magnesium Stearate . Stage 3 Tablet compression

Tablet compression