WO2006046100A1 - Pharmaceutical composition of alendronic acid - Google Patents
Pharmaceutical composition of alendronic acid Download PDFInfo
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- WO2006046100A1 WO2006046100A1 PCT/IB2005/003099 IB2005003099W WO2006046100A1 WO 2006046100 A1 WO2006046100 A1 WO 2006046100A1 IB 2005003099 W IB2005003099 W IB 2005003099W WO 2006046100 A1 WO2006046100 A1 WO 2006046100A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
- A61K31/663—Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
Definitions
- the present invention relates to a pharmaceutical composition of alendronic acid and pharmaceutically acceptable salts thereof.
- lactose when employed in a solid dosage form of an active ingredient having a basic nitrogen-containing functionality, can result in discoloration, chemical instability and loss of potency of the dosage form.
- the apparent incompatibility of lactose with basic nitrogen-containing active ingredients is believed to be due to the Maillard (or "browning") reaction in which the basic nitrogen (typically a primary or secondary amino group) of the active ingredient reacts with the "glycosidic" hydroxyl group of lactose ultimately resulting in the formation of brown pigmented degradation products.
- sugars having a "glycosidic" hydroxyl group such as glucose
- Other sugars having a "glycosidic" hydroxyl group also stimulate this degradation when employed as excipients in dosage forms of basic nitrogen-containing actives. Degradation of the active ingredient is particularly pronounced in the presence of water and/or elevated temperature. This problem can be solved by making a composition which is free of such excipients.
- a pharmaceutical composition suitable for oral administration to a human comprising: a) from about 0.5% to about 60% by weight of alendronic acid or pharmaceutically acceptable salt thereof; b) from about 10% to about 95% by weight of a non-reducing sugar or sugar alcohol such as mannitol, xylitol, sorbitol, inositol, sucrose and trehalose or mixtures thereof; c) from about 0.5% to about 20% by weight of a disintegrant such as starch, modified starch, croscarmellose sodium, crospovidone and sodium starch glycolate or mixtures thereof; and d) from about 0.1 % to about 10% by weight of lubricant/glidant such as colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate,
- a process for the preparation of pharmaceutical composition comprising the steps of- a) blending from about 0.5% to about 60% by weight of alendronic acid or pharmaceutically acceptable salt thereof; and from about 10% to about 95% by weight of a non-reducing sugar or sugar alcohol such as mannitol, xylitol, sorbitol, inositol, sucrose and trehalose or mixtures thereof, b) mixing the blend of step a) with about 0.5% to about 20% by weight of a disintegrant such as starch, modified starch, croscarmellose sodium, crospovidone and sodium starch glycolate or mixtures thereof; and, about 0.1% to about 10% by weight of lubricant/glidant such as colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated vegetable oil, sodium stearyl fumarate, sucrose esters of fatty acid, microcrystalline wax, yellow beeswax, white bees
- a method of treating or preventing osteoporosis comprising administering a pharmaceutical composition
- a pharmaceutical composition comprising: a) from about 0.5% to about 60% by weight of alendronic acid or pharmaceutically acceptable salt thereof; b) from about 10% to about 95% by weight of a non-reducing sugar or sugar alcohol such as mannitol, xylitol, sorbitol, inositol, sucrose and trehalose or mixtures thereof; c) from about 0.5% to about 20% by weight of a disintegrant such as starch, modified starch, croscarmellose sodium, crospovidone and sodium starch glycolate or mixtures thereof; and d) from about 0.1% to about 10% by weight of lubricant/glidant such as colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated vegetable oil, sodium stearyl fumarate, sucrose esters of fatty acid, microcrystalline wax, yellow beeswax,
- composition suitable for oral administration to a human comprising: a) from about 0.5% to about 60% by weight of alendronic acid or pharmaceutically acceptable salt thereof; b) from about'10% to about 95% by weight of mannitol; c) from about 0.5% to about 20% by weight of croscarmellose sodium; d) from about 0.1% to about 5% by weight of magnesium stearate; e) from about 0.1 % to about 5% by weight of talc; and f) from about 0.1% to about 5% by weight of colloidal silicon dioxide.
- a process for the preparation of pharmaceutical composition comprising the steps of: a) blending alendronic acid or pharmaceutically acceptable salts thereof and mannitol, b) mixing the blend of step a) with croscarmellose sodium, talc and colloidal silicon dioxide, c) optionally granulating the blend, d) lubricating the blend of step a) or granules of step b), and e) compressing into or filling into suitable size solid dosage form.
- mannitol provides a dual advantage, firstly, being a non-reducing sugar alcohol, it does not undergo Maillard reaction with alendronic acid; and secondly, due to good compressibility characteristics, it facilitates fast disintegration of tablets with high hardness. Additionally, such tablets when made with a direct compression method do not require the use of binder.
- compositions as used herein includes solid dosage forms such as tablets, capsules, pills and the like.
- the tablets can be prepared by techniques known in the art and contain a therapeutically useful amount of the alendronic acid or salts thereof and such excipients as are desirable to form the tablet by such techniques.
- Tablets and pills can additionally be given enteric coatings and other release-controlling coatings for the purpose of acid protection, easing swallowability, etc.
- the pharmaceutically acceptable salts of alendronic acid include ammonium salts, alkali metal salts such as potassium and sodium (including, but not limited to, mono-, di- and tri-sodium) salts, alkaline earth metal salts such as calcium and magnesium salts, salts with organic bases such as dicyclohexylamine salts, N-methyl-D-glucamine, and salts with amino acids such as arginine, lysine.
- the sodium salt may exist in any of the solid state which includes monohydrate, dihydrate, trihydrate, anhydrous, or any other polymorphic forms.
- non-reducing sugar or sugar alcohol can act as diluent in the formulation.
- a "non-reducing sugar” as used herein refers to a sugar or sugar alcohol without a glycosidic hydroxyl group or a sugar (or sugar alcohol) which is otherwise incapable of reaction with the basic nitrogen of a basic nitrogen-containing compound in a Maillard-type reaction.
- Examples of non-reducing sugar or sugar alcohol include mannitol, xylitol, sorbitol, inositol, sucrose and trehalose.
- the pharmaceutical composition may be prepared by a wet granulation technique, comprising the steps of blending alendronic acid or pharmaceutically acceptable salts thereof, non-reducing sugar or sugar alcohol and disintegrant; granulating with a granulating fluid or solution/dispersion of binder; drying and sizing the granules; optionally blending with pharmaceutically inert extragranular excipients; lubricating the granules/blend; compressing the lubricated blend into suitable sized tablets; and optionally coating with film forming polymer and coating additives.
- a wet granulation technique comprising the steps of blending alendronic acid or pharmaceutically acceptable salts thereof, non-reducing sugar or sugar alcohol and disintegrant; granulating with a granulating fluid or solution/dispersion of binder; drying and sizing the granules; optionally blending with pharmaceutically inert extragranular excipients; lubricating the granules/blend; compressing the lub
- the pharmaceutical composition may be prepared by a dry granulation technique, comprising the steps of blending alendronic acid or pharmaceutically acceptable salts thereof, non-reducing sugaror sugar alcohol and disintegrant; dry granulating the blend by roller compactor or slugging; lubricating the granules/blend; compressing the lubricated blend into suitable sized tablets; and optionally coating with film forming polymer and coating additives.
- the pharmaceutical composition may be prepared by a direct compression technique, comprising the steps of blending alendronic acid or pharmaceutically acceptable salts thereof, non-reducing sugar or sugar alcohol and disintegrant; lubricating the blend; directly compressing the lubricated blend into suitable sized tablets; and optionally coating with film forming polymer and coating additives.
- compositions may comprise other pharmaceutically acceptable excipients such as binders, surfactants and coloring agents.
- surfactants include both non-ionic and ionic (cationic, anionic and zwitterionic) surfactants suitable for use in pharmaceutical dosage forms.
- polyethoxylated fatty acids and its derivatives for example, polyethylene glycol 400 distearate, polyethylene glycol - 20 dioleate, polyethylene glycol 4 -150 mono dilaurate, polyethylene glycol -20 glyceryl stearate; alcohol - oil transesterification products, for example, polyethylene glycol - 6 corn oil; polyglycerized fatty acids, for example, polyglyceryl - 6 pentaoleate; propylene glycol fatty acid esters, for example, propylene glycol monocaprylate; mono and diglycerides, for example, glyceryl ricinoleate; sterol and sterol derivatives; sorbitan fatty acid esters and its derivatives, for example, polyethylene glycol - 20 sorbitan monooleate, sorbitan monolaurate; polyethylene glycol alkyl ether or phenols, for example, polyethylene glycol - 20 cetyl ether, polyethylene glycol
- Coloring agents include any FDA approved colors for oral use.
- the pharmaceutical composition may optionally be coated with functional and/or non-functional layers comprising film- forming polymers, if desired.
- film-forming polymers examples include ethylcellulose, hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, carboxymethyl cellulose, hydroxymethylcellulose, hydroxyethylcellulose, cellulose acetate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate; waxes such as polyethylene glycol; methacrylic acid polymers such as Eudragit ® RL and RS; and the like.
- commercially available coating compositions comprising film- forming polymers marketed under various trade names, such as Opadry® may also be used for coating.
- Croscarmellose sodium, talc and aerosil were also sifted through sieve and mixed with the blend of step 1.
- Magnesium stearate was sifted through sieve and added to the step 2 and mixed thoroughly.
- Blend of step 4 was compressed to tablets.
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Abstract
The present invention relates to a pharmaceutical composition of alendronic acid and pharmaceutically acceptable salts thereof.
Description
PHARMACEUTICAL COMPOSITION OF ALENDRONIC ACID
The present invention relates to a pharmaceutical composition of alendronic acid and pharmaceutically acceptable salts thereof.
Background of the Invention A variety of bisphosphonic acids have been disclosed as being useful in the treatment and prevention of diseases involving bone resorption. Representative examples may be found in the following: US 3,962,432; US 4,054,598; US 4,267,108; US 4,327,039; US 4,621,077; US 4,624,947; US 4,746,654; and US 4,922,077. Various methods for tablet formulation of bisphosphonic acids have been employed, however, they are not satisfactory.
For example, the use of the common diluent lactose, when employed in a solid dosage form of an active ingredient having a basic nitrogen-containing functionality, can result in discoloration, chemical instability and loss of potency of the dosage form. The apparent incompatibility of lactose with basic nitrogen-containing active ingredients is believed to be due to the Maillard (or "browning") reaction in which the basic nitrogen (typically a primary or secondary amino group) of the active ingredient reacts with the "glycosidic" hydroxyl group of lactose ultimately resulting in the formation of brown pigmented degradation products. Other sugars having a "glycosidic" hydroxyl group, such as glucose, also stimulate this degradation when employed as excipients in dosage forms of basic nitrogen-containing actives. Degradation of the active ingredient is particularly pronounced in the presence of water and/or elevated temperature. This problem can be solved by making a composition which is free of such excipients.
Attempts have been made to formulate bisphosphonates bearing basic nitrogen- containing functionality with lactose as diluent by eliminating water from the formulation process. A dry mix process using anhydrous lactose as a diluent avoids the enhanced degradation which occurs in the presence of water. Solid dosage forms prepared by such a process are exemplified in US 5,882,656.
Summary of the Invention
The inventors have developed pharmaceutical composition suitable for oral administration to a human, comprising alendronic acid, non-reducing sugar or sugar alcohol, disintegrant and lubricant/glidant. In one general aspect, there is provided a pharmaceutical composition suitable for oral administration to a human, comprising: a) from about 0.5% to about 60% by weight of alendronic acid or pharmaceutically acceptable salt thereof; b) from about 10% to about 95% by weight of a non-reducing sugar or sugar alcohol such as mannitol, xylitol, sorbitol, inositol, sucrose and trehalose or mixtures thereof; c) from about 0.5% to about 20% by weight of a disintegrant such as starch, modified starch, croscarmellose sodium, crospovidone and sodium starch glycolate or mixtures thereof; and d) from about 0.1 % to about 10% by weight of lubricant/glidant such as colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated vegetable oil, sodium stearyl fumarate, sucrose esters of fatty acid, microcrystalline wax, yellow beeswax, white beeswax or mixtures thereof. In another general aspect, there is provided a process for the preparation of pharmaceutical composition comprising the steps of- a) blending from about 0.5% to about 60% by weight of alendronic acid or pharmaceutically acceptable salt thereof; and from about 10% to about 95% by weight of a non-reducing sugar or sugar alcohol such as mannitol, xylitol, sorbitol, inositol, sucrose and trehalose or mixtures thereof, b) mixing the blend of step a) with about 0.5% to about 20% by weight of a disintegrant such as starch, modified starch, croscarmellose sodium, crospovidone and sodium starch glycolate or mixtures thereof; and, about 0.1% to about 10% by weight of lubricant/glidant such as colloidal silicon
dioxide, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated vegetable oil, sodium stearyl fumarate, sucrose esters of fatty acid, microcrystalline wax, yellow beeswax, white beeswax or mixtures thereof, c) optionally granulating the blend, d) lubricating the blend of step a) or granules of step b), and e) compressing into or filling into suitable size solid dosage form.
In one general aspect, there is provided a method of treating or preventing osteoporosis comprising administering a pharmaceutical composition comprising: a) from about 0.5% to about 60% by weight of alendronic acid or pharmaceutically acceptable salt thereof; b) from about 10% to about 95% by weight of a non-reducing sugar or sugar alcohol such as mannitol, xylitol, sorbitol, inositol, sucrose and trehalose or mixtures thereof; c) from about 0.5% to about 20% by weight of a disintegrant such as starch, modified starch, croscarmellose sodium, crospovidone and sodium starch glycolate or mixtures thereof; and d) from about 0.1% to about 10% by weight of lubricant/glidant such as colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated vegetable oil, sodium stearyl fumarate, sucrose esters of fatty acid, microcrystalline wax, yellow beeswax, white beeswax or mixtures thereof.
In another general aspect, there is provided pharmaceutical composition suitable for oral administration to a human, comprising: a) from about 0.5% to about 60% by weight of alendronic acid or pharmaceutically acceptable salt thereof; b) from about'10% to about 95% by weight of mannitol; c) from about 0.5% to about 20% by weight of croscarmellose sodium;
d) from about 0.1% to about 5% by weight of magnesium stearate; e) from about 0.1 % to about 5% by weight of talc; and f) from about 0.1% to about 5% by weight of colloidal silicon dioxide.
In another general aspect, there is provided a process for the preparation of pharmaceutical composition comprising the steps of: a) blending alendronic acid or pharmaceutically acceptable salts thereof and mannitol, b) mixing the blend of step a) with croscarmellose sodium, talc and colloidal silicon dioxide, c) optionally granulating the blend, d) lubricating the blend of step a) or granules of step b), and e) compressing into or filling into suitable size solid dosage form.
Use of mannitol provides a dual advantage, firstly, being a non-reducing sugar alcohol, it does not undergo Maillard reaction with alendronic acid; and secondly, due to good compressibility characteristics, it facilitates fast disintegration of tablets with high hardness. Additionally, such tablets when made with a direct compression method do not require the use of binder.
The term 'pharmaceutical composition' as used herein includes solid dosage forms such as tablets, capsules, pills and the like. The tablets can be prepared by techniques known in the art and contain a therapeutically useful amount of the alendronic acid or salts thereof and such excipients as are desirable to form the tablet by such techniques. Tablets and pills can additionally be given enteric coatings and other release-controlling coatings for the purpose of acid protection, easing swallowability, etc.
The pharmaceutically acceptable salts of alendronic acid include ammonium salts, alkali metal salts such as potassium and sodium (including, but not limited to, mono-, di- and tri-sodium) salts, alkaline earth metal salts such as calcium and magnesium salts, salts with organic bases such as dicyclohexylamine salts, N-methyl-D-glucamine, and salts with amino acids such as arginine, lysine. The sodium salt may exist in any of the solid state
which includes monohydrate, dihydrate, trihydrate, anhydrous, or any other polymorphic forms.
The non-reducing sugar or sugar alcohol can act as diluent in the formulation. A "non-reducing sugar" as used herein refers to a sugar or sugar alcohol without a glycosidic hydroxyl group or a sugar (or sugar alcohol) which is otherwise incapable of reaction with the basic nitrogen of a basic nitrogen-containing compound in a Maillard-type reaction. Examples of non-reducing sugar or sugar alcohol include mannitol, xylitol, sorbitol, inositol, sucrose and trehalose.
In one general aspect, the pharmaceutical composition may be prepared by a wet granulation technique, comprising the steps of blending alendronic acid or pharmaceutically acceptable salts thereof, non-reducing sugar or sugar alcohol and disintegrant; granulating with a granulating fluid or solution/dispersion of binder; drying and sizing the granules; optionally blending with pharmaceutically inert extragranular excipients; lubricating the granules/blend; compressing the lubricated blend into suitable sized tablets; and optionally coating with film forming polymer and coating additives.
In one general aspect, the pharmaceutical composition may be prepared by a dry granulation technique, comprising the steps of blending alendronic acid or pharmaceutically acceptable salts thereof, non-reducing sugaror sugar alcohol and disintegrant; dry granulating the blend by roller compactor or slugging; lubricating the granules/blend; compressing the lubricated blend into suitable sized tablets; and optionally coating with film forming polymer and coating additives.
In another general aspect, the pharmaceutical composition may be prepared by a direct compression technique, comprising the steps of blending alendronic acid or pharmaceutically acceptable salts thereof, non-reducing sugar or sugar alcohol and disintegrant; lubricating the blend; directly compressing the lubricated blend into suitable sized tablets; and optionally coating with film forming polymer and coating additives.
In addition to active ingredients, diluents, disintegrants and lubricants/glidants; the composition may comprise other pharmaceutically acceptable excipients such as binders, surfactants and coloring agents.
Surfactants include both non-ionic and ionic (cationic, anionic and zwitterionic) surfactants suitable for use in pharmaceutical dosage forms. These include polyethoxylated fatty acids and its derivatives, for example, polyethylene glycol 400 distearate, polyethylene glycol - 20 dioleate, polyethylene glycol 4 -150 mono dilaurate, polyethylene glycol -20 glyceryl stearate; alcohol - oil transesterification products, for example, polyethylene glycol - 6 corn oil; polyglycerized fatty acids, for example, polyglyceryl - 6 pentaoleate; propylene glycol fatty acid esters, for example, propylene glycol monocaprylate; mono and diglycerides, for example, glyceryl ricinoleate; sterol and sterol derivatives; sorbitan fatty acid esters and its derivatives, for example, polyethylene glycol - 20 sorbitan monooleate, sorbitan monolaurate; polyethylene glycol alkyl ether or phenols, for example, polyethylene glycol - 20 cetyl ether, polyethylene glycol - 10 - 100 nonyl phenol; sugar esters, for example, sucrose monopalmitate; polyoxyethylene - polyoxypropylene block copolymers known as "poloxamer"; ionic surfactants, for example, sodium caproate, sodium glycocholate, soy lecithin, sodium stearyl fumarate, propylene glycol alginate, octyl sulfosuccinate disodium, palmitoyl carnitine; and the like.
Coloring agents include any FDA approved colors for oral use.
The pharmaceutical composition may optionally be coated with functional and/or non-functional layers comprising film- forming polymers, if desired.
Examples of film-forming polymers include ethylcellulose, hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, carboxymethyl cellulose, hydroxymethylcellulose, hydroxyethylcellulose, cellulose acetate, hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, cellulose acetate trimellitate; waxes such as polyethylene glycol; methacrylic acid polymers such as Eudragit ® RL and RS; and the like. Alternatively, commercially available coating compositions comprising film- forming polymers marketed under various trade names, such as Opadry® may also be used for coating.
The invention is further illustrated by the following examples, which is for illustrative purpose only and do not limit the scope of invention .
EXAMPLE 1-5
Process: 1. Sodium Alendronate and Mannitol were sifted through sieve and blended geometrically.
Croscarmellose sodium, talc and aerosil were also sifted through sieve and mixed with the blend of step 1.
Magnesium stearate was sifted through sieve and added to the step 2 and mixed thoroughly.
Blend of step 4 was compressed to tablets.
EXAMPLE 6-8
Process: 1. Sodium Alendronate, Mannitol, Croscarmellose sodium and Magnesium Stearate were sifted through sieve and mixed geometrically.
2. The blend was passed through roll compactor and the compacts obtained were passed through sieve. 3. Croscarmellose sodium, Mannitol, talc and colloidal silicon dioxide were sifted through sieve and mixed with the compact of step 2. 4. Magnesium stearate was sifted through sieve and added to the step 3 and mixed. 55.. The blend was compressed into tablets.
While there have been shown and described what are the preferred embodiments of the invention, one skilled in the pharmaceutical formulation art will appreciate that various modifications in the formulations and process can be made without departing from the scope of the invention as it is defined by the appended claims.
Claims
We Claim: 1. A pharmaceutical composition suitable for oral administration to a human, comprising: a) from about 0.5% to about 60% by weight of alendronic acid or pharmaceutically acceptable salt thereof; b) from about 10% to about 95% by weight of a non-reducing sugar or sugar alcohol selected from the group consisting of mannitol, xylitol, sorbitol, inositol, sucrose and trehalose or mixtures thereof; c) from about 0.5% to about 20% by weight of a disintegrant selected from the group consisting of starch, modified starch, croscarmellose sodium, crospovidone and sodium starch glycolate or mixtures thereof; and d) from about 0.1 % to about 10% by weight of lubricant/glidant selected from the group consisting of colloidal silicon dioxide, stearic acid, magnesium stearate, calcium stearate, talc, hydrogenated vegetable oil, sodium stearyl fumarate, sucrose esters of fatty acid, microcrystalline wax, yellow beeswax, white beeswax or mixtures thereof. 2. The pharmaceutical composition of claim 1, wherein said composition is in the form of a tablet. 3. The pharmaceutical composition according to claim 1 , wherein pharmaceutically acceptable salts include ammonium salts, alkali metal salts such as potassium and sodium salts, alkaline earth metal salts such as calcium and magnesium salts, salts with organic bases such as dicyclohexylamine salts, N-methyl-D-glucamine, and salts with amino acids such as arginine, lysine. 4. The pharmaceutical composition according to claim 3, wherein pharmaceutically acceptable salt is sodium salt. 5. The pharmaceutical composition according to claim 4, wherein sodium salt is monohydrate, dihydrate or trihydrate, anhydrous or any other polymorphic form. 6. A pharmaceutical composition suitable for oral administration to a human, comprising:
a) from about 10% to about 60% by weight of alendronic acid or pharmaceutically acceptable salt thereof; b) from about 10% to about 95% by weight of mannitol; c) from about 0.5% to about 20% by weight of croscarmellose sodium; d) from about 0.1% to about 5% by weight of magnesium stearate; e) from about 0.1% to about 5% by weight of talc; and f) from about 0.1% to about 5% by weight of colloidal silicon dioxide. 7. A process for the preparation of pharmaceutical composition of claim 1 comprising the steps of- a) blending alendronic acid or pharmaceutically acceptable salt thereof and a non-reducing sugar or sugar alcohol, b) mixing the blend of step a) with a disintegrant, lubricant/glidant. c) optionally granulating the blend, d) lubricating the blend of step a) or granules of step b), and e) compressing into or filling into suitable size solid dosage form. 8. The process for the preparation of pharmaceutical composition according to claim 7 wherein granulation is carried out by a wet granulation or dry granulation. 9. The process for the preparation of pharmaceutical composition according to claim 8 wherein wet granulation is carried out with a granulating fluid or solution/dispersion of binder. 10. The process for the preparation of pharmaceutical composition according to claim 8 wherein dry granulation is carried out by roller compactor or slugging. 11. A method of treating or preventing osteoporosis comprising administering pharmaceutical composition of claim 1.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2083DE2004 | 2004-10-25 | ||
| IN2083/DEL/2004 | 2004-10-25 |
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| WO2006046100A1 true WO2006046100A1 (en) | 2006-05-04 |
| WO2006046100B1 WO2006046100B1 (en) | 2006-08-03 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008020305A2 (en) * | 2006-08-17 | 2008-02-21 | Aurobindo Pharma Limited | Solid dosage forms of bisphosphonic acids |
| WO2008023184A3 (en) * | 2006-08-24 | 2008-04-24 | Arrow Int Ltd | Solid dosage form |
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| WO2001028564A1 (en) * | 1999-10-20 | 2001-04-26 | Yuyu Industrial Co., Ltd. | Pharmaceutical compositions and preparations for treatment of metabolic bone disease |
| WO2001085176A1 (en) * | 2000-05-11 | 2001-11-15 | Instytut Farmaceutyczny | The solid oral pharmaceutical composition comprising a bisphosphonic acid derivative |
| US20030161878A1 (en) * | 2000-07-11 | 2003-08-28 | Dagmar Jasprova | Tablet obtained by direct compression comprising 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid as active ingredient |
| US20040138180A1 (en) * | 2002-10-03 | 2004-07-15 | Barr Laboratories, Inc. | Bisphosphonate composition and process for the preparation thereof |
| EP1407766A2 (en) * | 2002-10-07 | 2004-04-14 | Verisfield (UK) Ltd. | Pharmaceutical compositions that contain a salt of alendronic acid |
| GR1004660B (en) * | 2003-06-25 | 2004-08-25 | ������������, �������� ��� ����������� �������� �������� ��� �.�. ��������-������������ �.�. | Advanced alendronate sodium trihydrate pharmaceutical compositions and preparation methods thereof |
| EP1491199A1 (en) * | 2003-06-25 | 2004-12-29 | Pharmanel Pharmaceutical, Commercial and Industrial S.A. | Pharmaceutical compositions of alendronate sodium trihydrate and process for the preparation thereof |
| WO2005030177A2 (en) * | 2003-09-29 | 2005-04-07 | Cipla Limited | Pharmaceutical formulation with improved stability |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008020305A2 (en) * | 2006-08-17 | 2008-02-21 | Aurobindo Pharma Limited | Solid dosage forms of bisphosphonic acids |
| WO2008020305A3 (en) * | 2006-08-17 | 2008-05-08 | Aurobindo Pharma Ltd | Solid dosage forms of bisphosphonic acids |
| WO2008023184A3 (en) * | 2006-08-24 | 2008-04-24 | Arrow Int Ltd | Solid dosage form |
| US8697124B2 (en) | 2006-08-24 | 2014-04-15 | Arrow International Limited | Solid dosage form of coated bisphosphonate particles |
| US10420725B2 (en) | 2006-08-24 | 2019-09-24 | Allergan Pharmaceuticals International Limited | Solid dosage form of coated bisphosphonate particles |
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| Publication number | Publication date |
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| WO2006046100B1 (en) | 2006-08-03 |
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