FORM 2
THE PATENTS ACT 1970
(39 of l970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
TITLE OF THE INVENTION:
"In Situ Gelling Controlled Release Dosage Forms" 2. APPLICANT (S):
l (a) NAME: FDC Limited
(b)NATIONALITY: Indian company incorporated under the Companies
! Act, 1956
(c) ADDRESS: 142-48, S.V. Road, Jogeshwari (West), Mumbai - 400 102, Maharashtra, India.
T. PREAMBLE TO THE DESCRIPTION:
The following specification describes the invention and the manner in which it is to be performed.

Technical field of the invention -
The present invention relates to an in situ gelling controlled release dosage form for delivery of minerals within the absorption window of the gastrointestinal tract.
Background and prior art of the invention -
Minerals are micronutrients which are essential for physiological functioning of body such as growth, repair and regulations. Minerals, in general, are required by body in small quantity to carry out its various functions. Minerals are classified in two categories viz., major minerals and trace elements. Minerals such as calcium, iron, sodium and iodine are termed as major minerals since they are required in high concentration for normal body functioning; whereas some minerals such as zinc, cobalt, nickel, copper, molybdenum and manganese are required in very low concentration for normal physiological functioning and are termed as trace elements.
Calcium is an essential mineral for the development of bones in children, pregnant women and fractures of accident and physiological origin. Calcium in dietary supplements is sufficient for metabolism and growth. However, in certain pathological conditions body relies on calcium from other sources such as pharmaceutical composition and demineralization. Calcium is absorbed in the small intestine by two general mechanisms such as transcellular pathway and paracellular pathway. Transcellular uptake of calcium is negatively dependent on calcium intake. If calcium intake is high, calcium-binding protein mediated down regulation process reduces the extent of calcium absorption. Whereas, low calcium intake, results in calcium mediated up regulation mechanism favoring the absorption of calcium. Gastro-retentive controlled release dosage form offers low calcium concentration at the site of absorption for prolonged period of time and hence enhances absorption of calcium through calcium - binding protein mediated up regulation process. Calcium is widely used as organic and inorganic acid salts such as calcium carbonate, calcium citrate, calcium citrate malate etc. Unlike other calcium salts, calcium carbonate is least toxic. Mild side effect such as constipation can be avoided by delivering the calcium in a gradual manner using gastroretentive dosage form. Poor solubility of calcium carbonate especially in small intestine, is the major rate-limiting step for absorption of calcium from oral solid and liquid suspension dosage forms of calcium carbonate.

Gastroretentive dosage forms increase the extent of ionization and solubilization of calcium carbonate in stomach. The controlled release of solubilized calcium from dosage form provides better absorption of calcium in the intestine (absorption window of calcium). Calcium carbonate has excellent physioc-hemical properties such as low bulk density, pH dependent solubility, low dose and better stability. These properties are found to be ideal for development of floating drug delivery system wherein the dosage forms remain in the stomach for prolonged period of time. Calcium carbonate, in contact with gastric acid produces carbon dioxide that improves the floating behavior of dosage form, when the gas is entrapped in gel network. Acidic condition favors the absorption of calcium carbonate from stomach. Gastroretentive drug delivery system retains the drug in acidic pH and hence favors the absorption of calcium in proximal part of GIT.
The high level of patient compliance in taking oral dosage forms is due to the ease of administration and handling of these forms. Although lot of work have been done in the area of oral controlled drug delivery systems in the last two decades, these systems had limited success in the case of drugs with a poor absorption window in the GIT (Gastrointestinal Tract). To formulate a successful stomach specific or gastroretentive drug delivery system, several techniques are currently used such as hydrodynamically balanced systems (HBS) / floating drug delivery system, low density systems, raft systems incorporating alginate gels, bioadhesive or mucoadhesive systems, high density systems, superporous hydrogels and magnetic systems.
Various attempts have been made to retain the dosage form in the stomach as a way of increasing the gastric retention time. These attempts include introducing floating dosage forms (gas-generating systems and swelling or expanding systems), mucoadhesive systems, high-density systems, modified shape systems, gastric-emptying delaying devices and co-administration of gastric-emptying delaying agents. Among these, the floating dosage forms have been extensively explored and reported in literature. Floating dosage forms have a bulk density less than gastric fluids and so remain buoyant in the stomach contents, without getting affected by gastric emptying rate, for a prolonged period of time. While the system is floating on the gastric contents, the drug is released slowly at the desired rate from the system. After release of drug, the residual system is

emptied from the stomach. This result in an increased gastroretention time (GRT) and a better control of the fluctuations in plasma drug concentration. However, besides a minimal gastric content needed to allow the proper achievement of the buoyancy retention principle, a minimum level of floating force (F) is also required to keep the dosage form reliably buoyant on the surface of the meals.
In situ gels are drug delivery systems wherein the dosage forms which are in solid/liquid form before administration in the body, but once administered, undergo gelation. The formation of gel depends on factors like temperature modulation, pH change and presence of ions from which the drug gets released in a sustained and controlled manner. Various polymers that are used for the formulation of in situ gels include gellan gum, alginic acid, xyloglucan, chitosan, poly (DL-lactic acid), poly (DL-lactide-co-glycolide) and poly-caprolactone. Mainly in situ gels are administered by oral, ocular, rectal, vaginal, injectable and intraperitoneal routes. The in situ gel forming polymeric formulations offer several advantages like sustained and prolonged action in comparison to conventional drug delivery systems.
In conclusion, the primary requirement of a successful oral controlled release product focuses on increasing patient compliance along with plasma drug concentration which can be achieved by in situ gels as dosage forms. In addition, low density characteristics of in situ gel offers floating advantages, which retain the drug or dosage form for longer period of time in proximal part of gastrointestinal tract that improves extent of absorption. Exploitation of polymeric in situ gel for controlled release of various drugs provides a number of advantages over conventional dosage forms. Sustained and prolonged release of the drug, good stability and biocompatibility characteristics make the in situ gel dosage forms very reliable. Use of pharmaceutical polymers which are approved by many regulatory agencies including USFDA for in situ gel formulations make them more acceptable and excellent drug delivery systems. Oral in situ gels offer distinct advantage likes easy swallowing, especially in pediatric and geriatric populations.
US 2004/0180088 provides a gastroretentive controlled drug deliver}' system comprising (a) a controlled release core comprising a drug, a highly swellable polymer and a gas generating agent, said core being capable of swelling and achieving floatation rapidly

while maintaining its physical integrity in gastrointestinal fluids for prolonged periods and (b) a rapidly releasing coat composition comprising the same drug as in the core and pharmaceutically acceptable excipients, wherein the coating composition surrounds the core such that the system provides a biphasic release of the drug in gastrointestinal fluids.
The said prior art is a complex manufacturing process and moreover the system consists of two compartments such as immediate release and controlled release which may result in dose dumping if the system fails to control in any physiologically altered conditions.
US 2009/0087484 claims a formulation for increasing the bioavailability of an orally administered hydrophilic macromolecule, the formulation comprising a hydrophilic macromolecule, a permeation enhancer and a carrier capable of forming a bioadhesive gel. the formulation being formulated such that the formulation is released within the gastrointestinal tract as a liquid and forms a bioadhesive gel in situ after the formulation has some opportunity to spread across the surface of the gastrointestinal mucosal membrane.
The dosage form in the above prior art is basically designed for delivery of macromolecules such as proteins and peptides.
US 7485322 relates to a novel modified release pharmaceutical composition comprising the coated capsule body, coated or uncoated capsule cap, at least one tablet and granulate comprising active substance. The capsule body and cap are assembled so as to encapsulate at least the tablet and granulate together with trapped gas and at least an exposed portion of the capsule body of the assembled capsule is coated with a coating which is substantially insoluble or poorly soluble in an acidic aqueous medium wherein the assembled capsule floats or at least remains buoyant m the acidic aqueous medium for at least about an hour.
The said prior art is restricted to only capsule dosage form which remains buoyant in the acidic aqueous medium of the stomach for an hour and moreover the coating of the capsule is very cumbersome.

US 4140760 discloses a pharmaceutical composition for the suppression of gastric reflux comprising sodium alginate, sodium bicarbonate, calcium carbonate and sodium salt of an acrylic polymer cross-linked with 1% allyl-sucrose. The said ingredients react in the presence of gastric acid in the stomach to form a carbonated get in which alginic acid molecules are cross-linked by calcium ions to strengthen the gel matrix.
The above mentioned prior art is related to development of dosage form for treatment of gastro-oesophageal reflux disorders.
US 6348502 claims a pharmaceutical composition for the treatment of gastro-oesophageal reflux disease which includes a carrier vehicle and a gastroprotective agent. The carrier vehicle is either capable of forming a floating barrier layer on contact with gastric acid or of forming a bioadhesive film before contact with gastric acid occurs, so as to protect gastric mucosa from irritation by the gastric acid. A preferred active ingredient is capsaicin. The carrier vehicle preferably contains alginate or cross-linked polyacrylic acid.
The said prior art describes the dosage forms for the treatment of gastro-oesophageal diseases.
The aforementioned prior art documents do not disclose an in situ gel controlled release drug delivery of the minerals such as calcium, iron, magnesium, selenium, copper, zinc, manganese, cobalt, nickel, potassium, sodium, phosphorus, sulphur, chloride, chromium, iodine and molybdenum.
Objective of the invention -
Accordingly, main objective of the present invention is to provide an in situ gel formulation for delivery of minerals such as calcium, iron, magnesium, selenium, copper, zinc, manganese, cobalt, nickel, potassium, sodium, phosphorus, sulphur, chloride, chromium, iodine and molybdenum, for enhanced bioavailability and reduced dose related side effects.

Another objective of the present invention is to provide in situ gelling controlled release dosage form to deliver the formulation in the absorption window of the gastrointestinal tract useful for treating post operative conditions which lead to mineral deficiency and as a prophylactic measure.
The present invention is used for dietary minerals such as calcium, iron, magnesium, selenium, copper, zinc, manganese, cobalt, nickel, potassium, sodium, phosphorus, sulphur, chloride, chromium, iodine and molybdenum for patients, like pregnant women, growing children, fracture, having mineral deficiency.
Summary of the invention -
In accordance with the above objectives, the present invention provides an in situ gel formulation for delivery of minerals in the absorption window of the gastrointestinal tract for enhanced bioavailability and reduced dose related side effects.
Detailed description of the invention -
The invention will now be described in detail so that various aspects thereof may be more fully understood and appreciated.
Most of the minerals are absorbed from the proximal part of GIT such as stomach and duodenum. In general, mineral absorption is an active and/or carrier mediated transport process and hence the absorption of minerals is subjected to saturation. Conventional dosage forms of minerals provide inadequate time for absorption and hence offer poor bioavailability. There is an absolute need for delivery system which provides adequate gastric retention time for absorption of minerals from GIT. Gastroretentive controlled delivery of calcium has several advantages over conventional delivery systems. Calcium being a divalent cation gets absorbed in proximal part of GIT. Immediate release dosage forms deliver calcium in stomach which passes quickly through the proximal GIT due to short gastroretention time. When the delivered calcium reaches to the distal part of GIT, no absorption takes place and calcium gets excreted through faeces, thus providing poor bioavailability-. Moreover, sudden release of calcium in GIT results in super-saturation of calcium resulting in poor solubility of calcium in GIT. thus offering poor bioavailability and clinical efficacy. Gastroretentive dosage forms of calcium are designed to release the

calcium in the absorption window (proximal part of GIT) in the controlled manner to avoid supersaturation of carriers. Better bioavailability can be expected from in situ gels which gradually release the drug in stomach.
Thus the present invention describes an in-situ gelling pharmaceutical composition for delivery of minerals, comprising one or more minerals, in-situ gelling polymer(s), a viscosity modifier and at least one pharmaceutically acceptable excipient, in a controlled-release oral dosage form, wherein the minerals are selected from calcium, iron, magnesium, selenium, copper, zinc, manganese, cobalt, nickel, potassium, sodium, phosphorus, sulphur, chloride, chromium, iodine and molybdenum.
In situ gelling oral dosage forms of present invention deliver the mineral(s) within the
absorption window of the gastrointestinal tract with enhanced bioavailability and reduced
dose related side effects.
The compositions of the present invention is used in the treatment of patients like
pregnant women and growing children, fractures and mineral deficiency. It is also used to
treat post operative conditions which lead to mineral deficiency and as a prophylactic
measure.
While each new development has improved oral delivery of drugs, increased efficacy of delivery is still needed. The present invention satisfies the above need by providing oral drug formulations with increased selectivity and efficacy of mineral delivery.
Thus, the present invention provides oral drug formulations with increased selectivity and efficacy of delivery to the stomach or small intestine or both. A composite formulation has been developed for selective, high efficacy delivery to specific regions of the gastrointestinal tract. The efficacious delivery of minerals to their site of absorption in the body requires addressing of some inherent obstacles.
The present invention encompasses nutritional mineral supplements either alone or in combinations which comprises a supplemental amount of a source of calcium, magnesium, zinc, iron, phosphorous, manganese, molybdenum, selenium, vanadium, copper preferably from the source of calcium for example calcium carbonate, calcium

gluconate, calcium citrate malate, dibasic calcium phosphate, calcium lactobionate and calcium hypophosphate, and iron salts such as sodium feredetate. ferrous ascorbate and ferrous fumarate.
The present invention describes controlled release stomach specific delivery of minerals, more preferably delivery of calcium alone or in combination with other minerals.
In situ gelling polymers offer low viscosity liquid product, thus making it convenient to pour. Such dosage forms when administered orally, form gel in stomach and offers rigid liquid gel matrix which act as barrier for drug release. The bicarbonates incorporated in the formulation releases the carbon dioxide on reacting with gastric acid. The released carbon dioxide is entrapped by gel matrix and thus provides low density of gel matrix when compared with gastric fluid. The low density gel floats in the stomach, providing prolonged gastric retention time, and thus facilitating the stay of drug in absorption window. Controlled release delivery of minerals, achieved by liquid-gel matrix, prevents super-saturation of minerals at the absorption site.
Accordingly, an in-situ gelling pharmaceutical composition for delivery of minerals, comprising one or more minerals, in-situ gelling polymer(s) in the range of 0.01% to 60%; viscosity modifier(s) in the range of 0.01% to 5% w/v and at least one pharmaceuticaily acceptable excipient, in a controlled-release oral dosage form.
The present invention employs in situ gelling agents alone or in combination, selected from the group but not limited to thermo-reversible polymers. pH triggered gelling polymer, ionic gelling polymers, enzyme induced gelling polymers and substrate specific gelling polymers preferably thermoreversible polymers, pH triggered gelling polymer and ionic gelling polymers. The in situ gelling polymer(s) are used in the range of 0.01% to 60%.
The thermo-reversible polymers used in the present invention are selected from methylcellulose, N-isopropylacrilamide copolymer, and poloxamers such as polyoxyethylene, polyoxypropylene and copolymer thereof. The ionic gelling polymers used in the present invention are selected from but not limited to alginic acid, salts of

alginic acid, gelatin, styrene polymers, acrylic acid derivatives, locust bean gum. guar gum, xanthan gum. carrageenans and gellan gum. The pH triggered gelling agents used in the present invention are selected from polyacrylic acid, polyacryl amides, polysaccharides, esters of acetic acid, succinic acid and phthalic acid, and methacrylic acid derivatives.
The present invention includes viscosity modifier selected from gum arabic. tragacanth, carrageenan, acacia gum, xanthan gum. pectins, cellulose derivative like hydroxypropylrnethyicellulose, hydroxyethylcellulose, carboxymethylcellulose. sodium carboxymethylcellulose, ethylcellulose, dioxypropylcellulose and carboxyvinyl polymers commercially known as Carbopol, and mixtures thereof. The viscosity modifiers are present in the range of 0.01% to 5% w/v preferably 0.05% to 5% and most preferably 0.1% to 2.5%. Viscosity modifiers are incorporated in the formulation for improving content uniformity by reducing sedimentation, for increasing the gel strength and thus leading to controlled release profile.
The pharmaceutical!}' accepted excipient is selected as per the dosage form, consisting of preservatives, pH modifiers or buffers, sweetners, flavorants, diluents, binders, lubricants and vehicles.
The present invention includes effective amount of preservative such as halogenated compounds, sodium benzoate, sorbates such as potassium sorbate, salts of edetate (also known as salts of ethylenediaminetetraacetic acid (EDTA) such as disodium edetate), benzalkonium chloride and parabens (such as methyl, ethyl, propyl and butyl p-hydroxybenzoic acid esters). Preferably the preservative is present in the range of from about 0.0lw/v to about 0.4% w/v composition.
The present invention includes pH modifiers or buffers to maintain the pH of the final composition within a certain desired range. pH often has a substantial effect on stability and so the pH chosen should enhance stability of the formulation overall. Thus, the pH modifiers used in accordance with the present invention may be any pharmaceutical grade acid or base which is capable of maintaining the pH within an acceptable range. pH modifiers are generally used within the range of about 0.005 to about 1% w/v most

preferably about 0.0! to about 0.5% vv/v. Sodium citrate is preferred in the proportion of 0.l%-0.5%w/v.
The present invention includes sweeteners from sugars like sucrose, fructose, dextrose and glucose, sweet polyhydric alcohols like glycerin, sorbitol and mannitol. artificial sweeteners like aspartame, sucralose, acesulfame potassium, lactilol, cyclamates and saccharin preferably sucralose.
The present invention includes flavorants or flavors to enhance the organoleptic qualities of the final composition. Flavorants can therefore include vanilla, American icecream, shahi gulab, strawberry, cherry, grape, lemon, lime, orange, peppermint, spearmint, cinnamon, chocolate and any desired combinations thereof. The most preferable flavor included in the composition is American icecream. Flavorants will typically be added in amounts of from about 0.0005% to about 20% w/v. preferably about 0.001% to about 5% w/v.
The vehicle component serves as the external phase of the suspensions. The vehicle may be comprised of water, glycerin, sorbitol, propylene glycol or mixtures thereof. The vehicle component may contain glycerin upto about 50%. The vehicle may also comprise propylene glycol upto about 20% w/v or from about 3% to about 10% w/v. Preferably purified water comprises the bulk of the vehicle component comprising from about 25% to about 95% w/v of the formulation, most preferably from 55% to about 90% w/v.
The present invention includes oral dosage forms such as tablets, capsules, granules,
powders for oral suspensions, solution, suspension and syrup.
The present invention is exemplified by the following examples which are provided for illustration only and should not be construed to limit the scope of the invention.

EXAMPLES
TABLETS
Example 1:

Sr. No. Ingredient mg/tablet
1 Sodium Feredetate 231 mg
2 Xanthan gum 109mg
3 Geilan gum 80 mg
4 Calcium Carbonate l00mg
5 Microcrystalline Cellulose 80 mg
6 Sodium Bicarbonate 50 mg
7 Magnesium Stearate 6 mg
8 Colloidal silicon dioxide 4 mg
9 Isopropyl alcohol q.s
10 Dichloromethane
q.s
1. Weighing and sieving ingredients (1-6) through 40 mesh;
2. blending the ingredients of step 1 in octagonal blender for 30 mins;
3. granulating the blended material of step 2 with isopropyl alcoho!:dichloromethane in the ratio of 70:30;
4. drying granules of step 3 and reducing the size of the granules by passing the same through 30 mesh;
5. blending the granules of step 4 with colloidal silicon dioxide and lubricating with magnesium stearate and
6. punching the lubricated granules using 9 mm standard concave punches.
In vitro dissolution profile for Sodium Feredetate Tablets

Time (hrs) % drug
dissolution in
0.1NHCI
0.5 20
1 33

2 45
4 68
6 85
8 98
Example 2

Sr.
No. Ingredient mg/tablet
1 Calcium Carbonate 500 mg
2 Sodium Alginate 250 mg
3 Xanthan gum 101 mg
4 Microcrystalline Cellulose 99 mg
5 Magnesium Stearate 6 mg
6 Colloidal silicon dioxide 4mg
7 Water q.s.
1. Weighing and sieving Ingredients (1-4) through 40 mesh;
2. blending the ingredients of step 1 in octagonal blender for 30 mins;
3. granulating the blended material of step 2 with water;
4. drying granules of step 3 and reducing the size of the granules by passing the same through 30 mesh;
5. blending the granules of step 4 with colloidal silicon dioxide and lubricating with magnesium stearate and
6. punching the lubricated granules using 9 mm standard concave punches.
Example 3

Sr. No. Ingredient mg/tablet
1 Magnesium oxide 400 mg
2 Sodium Alginate 200 mg
3 Carbopol 971 80 mg
4 Microcrystalline Cellulose 80 mg
5 Calcium Carbonate l00mg

6 Calcium Stearate 6mg
7 Colloidal silicon dioxide 4mg
8 Isopropyl alcohol q.s.
9
1 Water
q.s,
1. Weighing and sieving Ingredients (1-5) through 40 mesh;
2. blending the ingredients of step 1 in octagonal blender for 30 mins;
3: granulating the blended material of step 2 with isopropyl alcohol:water in the ratio of60:40;
4. drying granules of step 3 and reducing the size of the granules by passing the same through 30 mesh;
5. blending the granules of step 4 with colloidal silicon dioxide and lubricating with calcium stearate and
6. punching the lubricated granules using 9 mm standard concave punches.
SUSPENSION Example 4

Sr. No. Ingredient mg/5 ml
1 Calcium Carbonate 500 mg
2 Sodium Alginate 37.5 mg
Sodium Citrate 5 mg
4 Xanthan Gum 5 mg
5 Orange flavor 0.013 ml
6 Methylparaben sodium 10 mg
7 Propylparaben sodium 1 mg
8 Sunset yellow 2mg
9 Sucralose 5mg
10 Water Purified q.s.
1. Dissolving Sodium alginate and xanthan gum in one half quantity of purified water;
2. dissolving all other ingredients and suspending in one fourth of purified water and

3. mixing gradually solution of step 1 and step 2 and making the final volume with remaining quantity of water.
In vitro dissolution profile for Calcium Carbonate suspension

Time (hrs) % drug
dissolution in
0.1NHCI
0.5 28
1 45
2 63
4 79
6 96
Example 5

S No. ingredients 'mg/μm
1 Magnesium Oxide 400 mg
2 HPMCLV 100 l00mg
3 Gellan gum 120 mg
4 Sodium Bicarbonate 50 mg
5 Calcium Carbonate 50 mg
6 Shahi gulab flavor 0.01 ml
7 Acesulfame 4mg
8 Ponceau 4R Supra 0.25 mg
9 Bronopol 5mg
10 Water purified q.s.
1. Dissolving HPMC and gellan gum in one half quantity of purified water;
2. dissolving all other ingredients and suspending in one fourth of purified water and
3. mixing gradually solution of step 1 and step 2 and making the final volume with remaining quantity of water.

Example 6

Sr. No. Ingredient mg/5 ml
] Sodium Feredetate 231 mg
2 Sodium Alginate 37.5 mg
3 Carbopol 971 70 mg
4 Calcium Carbonate 50 mg
5 Sucralose 5 mg
6 Sodium Citrate 5mg
7 American Ice cream 6 mg
8 Methylparaben sodium l0 mg
9 Propylparaben sodium 1 mg
10 Erythrosine 0.15 mg
11 American Ice cream 6mg
12 Water Purified q.s.
1. Dissolving Sodium alginate and carbopol 971 in one half quantity of purified water;
2. dissolving all other ingredients and suspending in one fourth of purified water and
3. gradually mixing solution of step t and 2 and making the final volume with remaining quantity of water.
Example 7

Sr.
No.
Ingredient mg/5 ml
1 Calcium Citrate Malate 300 mg
2 Gellan gum 37.5 mg
3 Pluronic 100 mg
4 Sodium Bicarbonate 50 mg
5 Sodium Citrate 5mg
6 Acesulfame 4 mg
7 Bronopol 5 mg
8 Orange flavour 0.013 ml
9 Sunset yellow 0.25 mg
10 Water Purified q.s.
1. Dissolving Gellan gum in one fourth quantity of purified water;

2. dispersing Pluronic in cold water and allowing to settle for 12 hrs to get clear solution;
3. dissolving all other ingredients and suspending in one fourth of purified water and
4. gradually mixing solutions of step 1, step 2 and step 3 and making the final volume with remaining quantity of water.
SYRUP
Example 8

Sr.
No. Ingredient mg/5ml
1 Sodium Feredetate 231 mg
2 Sodium Alginate 37.5 mg
Hydroxyethyl cellulose 15 mg
4 Menthol 35 mg
5 Sodium Benzoate 50 mg
6 Sucrose 100 mg
7 Sodium Bicarbonates 40 mg
8 Calcium chloride 5 mg
9 Shahi gulab 0.02 ml
10 11 Ponceau Supra 0.25 mg

Water q.s.
1. Dissolving Sodium alginate and hydroxyethyl cellulose in one half quantity of purified water;
2. dissolving all other ingredients and suspending in one fourth of purified water and
3. gradually mixing both the above liquids and making the final volume with remaining quantity of water.
CAPSULE
Example 9

Sr
No. Ingredients mg/capsule
1 Calcium Carbonate 1250 mg
2 Sodium Alginate 300 mg

... 3 Carbopol 150mg
4 Colloidal Silicon Dioxide 15 mg
5 Isopropylalcohol q.s.
6 Water q.S.
1. Weighing and sieving Ingredients (1 -3) through 40 mesh;
2. blending the ingredients of step 1 in octagonal blender for 30 mins;
3. granulating the blended material of step 2 with isopropyl alcohol : water in the ratio of 50:50;
4. drying granules of step 3 and reducing the size of the granules by passing the same through 30 mesh;
5. blending the granules of step 4 with colloidal silicon dioxide and
6. filling the blended granules of step 5 in capsules.
In vitro dissolution profile for Calcium Carbonate Capsule

Time (hrs) % drug
dissolution in
O.1NHCI
0.5 29
1 38
2 53
4 68
6 83
8 99

We claim:
1. Art in-situ gelling pharmaceutical composition for delivery of minerals, comprising one or more minerals, in-situ gelling polytner(s) in the range of 0.01% to 60%w/v, viscosity modifier(s) in the range of 0.01% to 5% w/v and at least one pharmaceutically acceptable excipient, in a controtled-release oral dosage form for delivery of minerals within the absorption window of the gastrointestinal tract.
2. The in-situ gelling pharmaceutical composition according to claim 1, wherein the one or more minerals are selected from source of calcium, magnesium, zinc, iron, phosphorous, manganese, molybdenum, selenium, vanadium or copper preferably sources of calcium and iron.
3. The in-situ gelling pharmaceutical composition according to claim 1, wherein the in-situ gelling polymer(s) are selected from thermoreversibie polymers, pH triggered gelling polymer, ionic gelling polymers, enzyme induced gelling polymers and substrate-specific gelling polymers preferably thermoreversibie polymers, pH triggered gelling polymer and ionic gelling polymers.
4. The in-situ gelling pharmaceutical composition according to claim 3, are selected from methylcellulose; N-isopropylacrilamide copolymer, poloxamers such as polyoxyethylene, polyoxypropylene and copolymer thereof, polyacrylic acid, polyacryl amides, polysaccharides, esters of acetic acid, succinic acid and phthalic acid, methacrylic acid derivatives, alginic acid, salts of alginic acid, gelatin, styrene polymers, acrylic acid derivatives, locust bean gum, guar gum and gellan gum.
5. The in-situ gelling pharmaceutical composition according to claim 1, wherein the viscosity modifier is selected from gum arable, tragacanth, carrageenan, acacia gum, xanthan gum, pectins, cellulose derivative like hydroxypropylmethylcellulose, hydroxyethylcellulose, carboxymethylcellulose, sodium carboxymethyl cellulose, ethylcellutose. dioxypropyicellulose and carboxyvinyl polymers and their mixtures.

6. The in-situ gelling pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable excipient is selected as per the dosage form, consisting of preservatives, pH modifiers, buffers, sweetners, flavorants, diluents, binders, lubricants and vehicles.
7. The in-situ gelling pharmaceutical composition according to claim 1, wherein the controlled-release oral dosage form include tablets, capsules, granules, powders for oral suspensions, solution, suspension and syrup.