MX2007014056A - Solid pharmaceutical composition for the oral administration of ibandronaic acid or salts or a pharmaceutically acceptable hydrate thereof, process for the preparation of said composition by direct compression, pharmaceutical formulations containing - Google Patents

Abstract

The present invention refers to a solid pharmaceutical composition in a unit dose form for the oral administration of ibandronaic acid that is obtained by a direct compression process, the composition including from about 30% to about 37% by weight of ibandronaic acid or a salt or a pharmaceutically acceptable hydrate thereof, at least a diluting agent in an amount ranging from about 55% to about 65% by weight, at least a disintegrating agent in an amount ranging from about 0.5% to 1.5% by weight, and at least a lubricating agent in an amount ranging from about 4.5% to about 5.5% by weight. The invention also comprises a direct compression process for the preparation of said compositions, as well as pharmaceutical coated formulations comprising said compositions and a process for the preparation of the aforementioned coated pharmaceutical formulations.

Description

SOLID PHARMACEUTICAL COMPOSITION FOR ORAL ADMINISTRATION OF IBANDRONIC ACID OR A PHARMACEUTICALLY ACCEPTABLE SALT OR HYDRATE OF THE SAME, PROCEDURE FOR PREPARING SUCH COMPOSITION THROUGH DIRECT COMPRESSION, PHARMACEUTICAL FORMULATIONS THAT CONTAIN IT AND PROCEDURE TO PREPARE THOSE FORMULATIONS FIELD OF THE INVENTION The present invention relates generally to solid pharmaceutical compositions in unit dosage form for oral administration of a diphosphonic acid. Said compositions present an improved stability and a more efficient manufacturing methodology. In particular, the present invention relates to a pharmaceutical composition containing ibandronic acid, or a pharmaceutically acceptable salt or hydrate thereof, preferably as a monosodium ibandronate monohydrate, to a process for its preparation by direct compression, to pharmaceutical formulations containing it a process for the preparation of said formulations.

BACKGROUND OF THE INVENTION Diphosphonic acids and their salts, usually referred to as diphosphonates or bisphosphonates, are known, in particular due to their application as active ingredients for the treatment of diseases and disorders of the bones. These diseases and disorders include, for example, alterations in calcium metabolism such as osteoporosis and hypercalcemia. Among the most commonly used diphosphonic acids are ibandronic acid, risedronic acid, pamidronic acid, zoledronic acid, alendronic acid and clodronic acid, among others. The compounds or their formulations are described, for example, in the patents or patent applications US 4687767, US 4666895, US 4859472 (clodronate, wet granulation), EP 186405 (risedronate), EP 613373 (risedronate, enteric formulation), and Argentine applications as AR 001225 A1 and AR001226 A1 (method of treatment of osteoporosis with phosphonates), AR 252531 (procedure for preparing diphosphonic acids), AR015946 A1 (formulation of bisphosphonates with absorption enhancers), AR019242 A1 (preparation of compositions by fluidized bed granulation), AR020017 A1 (use of ibandronate for osseointegration of prosthesis), AR027245 A1 (parenteral bisphosphonate compositions), AR033671 A1 (bisphosphonate gel compositions for subcutaneous administration) and AR034199 A1 (liquid ibandronate compositions with pH regulators). However, the known compositions have various drawbacks such as oral incompatibilities, adverse effects on the gastrointestinal tract, lack of flexibility in the administration regimens, slow disintegration of the formulation during its administration and even disadvantages in the processing of the compositions as in the filling of capsules and the adherence of the components to the compression dump dies. It is also known that high doses of ibandronate monosodium are complex to process from the point of view of pharmaceutical galenic formulations, since the high amounts of active ingredient must be granulated to achieve adequate fluidity and compressibility and a stable dosage unit dosage form. and with good dissolution speed. This can be seen in the publication WO 2004/05673 A1 (equivalent to RA 037560 A1) where a process of wet granulation is used where a superdisintegrant is added externally and internally to the granules containing the monosodium ibandronate. Consequently, there is a need still not satisfied with new diphosphonate formulations that overcome the disadvantages found with the compositions of the previous art. In particular, formulations of a solid for immediate oral administration where the disintegration in the gastrointestinal tract rapidly exposes the crystals of the active ingredient.

BRIEF DESCRIPTION OF THE FIGURE Figure 1 shows a graph of the dissolution profile of the compositions of the present invention compared to a known commercially available product.

DESCRIPTION OF THE INVENTION It has now been found that by means of the direct compression technique and using certain components and proportions, solid pharmaceutical compositions for oral administration of diphosphonic acids are obtained which overcome the problems presented by the compositions of the state of the art. The present invention provides a pharmaceutical composition of ibandronic acid, preferably in its form of monosodium ibandronate monohydrate, high dose and concentration in unit dosage form (coated tablets) obtained by mixing excipients prepared and suitable to be processed by the known technique in art as "Direct Compression". Unexpectedly it has been found that a pharmaceutical composition of ibandronate monosodium monohydrate in high concentrations using suitable excipients solves the problem of the need to employ the granulation technique, that is to say, previous formation of granules of said active principle and excipients. In this way it is possible to improve the dissolution profiles, the stability and the productive steps to obtain a safe and effective medication and very easy administration in humans.

Accordingly, an object of the present invention is a new solid pharmaceutical composition in unit dosage form for oral administration of ibandronic acid, preferably in the form of ibandronate monosodium monohydrate, prepared by a mixing process and subsequent direct compression of its ingredients. The new pharmaceutical compositions of the invention contain up to 330 mg of ibandronic acid, preferably as monosodium ibandronate monohydrate, preferably up to 200 mg, especially compositions containing 150 mg and more preferably up to 100 mg of ibandronic acid. Accordingly, an object of the invention is a solid pharmaceutical composition in unit dosage form for oral administration, prepared by direct compression, comprising: ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 30 to 37% by weight of said dosage form; at least one diluent in an amount of about 55 to 65% by weight of said dosage form; at least one disintegrating agent in an amount of about 0.5 to 1.5% by weight of said dosage form; and at least one lubricant in an amount of about 4.5 to 5.5% by weight of said dosage form. In a preferred embodiment of the invention, solid pharmaceutical compositions are provided in unit dosage form for oral administration, prepared by direct compression, comprising: ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 32 to 35% by weight of said dosage form; at least one diluent in an amount of about 57 to 62% by weight of said dosage form; at least one disintegrating agent in an amount of about 0.7 to 1.2% by weight of said dosage form; and at least one lubricant in an amount of about 4.7 to 5.2% by weight of said dosage form. In a more preferred embodiment of the invention, solid pharmaceutical compositions are provided in unit dosage form for oral administration, prepared by direct compression, comprising: ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 34% in weight of said dosage form; at least one diluent in an amount of about 60% by weight of said dosage form; at least one disintegrating agent in an amount of about 1% by weight of said dosage form; and at least one lubricant in an amount of about 5% by weight of said dosage form. In the most preferred embodiment of the invention, solid pharmaceutical compositions in unit dosage form for oral administration, prepared by direct compression, constitute a tablet. In preferred embodiments of the invention, ibandronic acid is present in the form of its monohydrated monosodium salt. The diluent used in the compositions of the present invention can be selected from any of those normally used in the pharmaceutical industry and is not restricted by any particular condition.

In preferred embodiments of the invention, the at least one diluent is selected from the group of microcrystalline cellulose, preferably silicified, cellulose gel, microfine cellulose, cellulose powder or crystalline cellulose. Lactose for direct compression, anhydrous lactose for direct compression, hydrated lactose for direct compression, Cellactose 80® (co-precipitated microcrystalline cellulose and lactose), Tabletose 80® (lactose for direct compression), agglomerated lactose, mannitol, calcium dibasic phosphate can also be used dihydrate, calcium sulfate dihydrate and mixtures thereof. Silicified microcrystalline cellulose is preferred. Likewise, the disintegrating agent used in the compositions of the present invention can be selected from any of those normally used in the pharmaceutical industry and is not restricted by any particular condition. In preferred embodiments of the invention, the at least one disintegrant is selected from the group of cross-linked sodium carboxymethylcellulose, sodium starch glycolate, cross-linked povidone, polyvinylpolypyrrolidone and mixtures thereof. Sodium carboxymethylcellulose crosslinked is preferred. Similarly, the lubricating agent used in the compositions of the present invention can be selected from any of those normally used in the pharmaceutical industry and is not restricted by any particular condition. In preferred embodiments of the invention, the at least one lubricating agent is selected from sodium stearyl fumarate, talc and hydrogenated vegetable oil, such as for example the product marketed under the brand Lubritab® (hydrogenated vegetable oil) and mixtures thereof. A further object of the present invention is a pharmaceutical formulation comprising a pharmaceutical composition in accordance with any of the embodiments set forth above in unit dosage form coated with a pharmaceutically acceptable coating.

The coating and coating compositions and agents used in the formulations of the present invention can be selected from any of those normally used in the pharmaceutical industry and is not restricted by any particular condition. In preferred embodiments of the formulations of the present invention, the coating or coating composition is selected from: methacrylic acid derivatives in an amount of about 1 to 4% by weight of said coated pharmaceutical formulation; diethyl phthalate in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation and talc in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation, or hydroxyethylcellulose in an amount of about 1 to 4. % by weight of said coated pharmaceutical formulation; triacetin in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation and magnesium carbonate in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation. In an even more preferred embodiment of this object of the present invention, the pharmaceutical formulation comprises: a pharmaceutical composition according to any of the embodiments set forth above, coated with a coating which in turn comprises: hydroxypropylmethylcellulose in an amount of about 1 to 4% by weight of said coated pharmaceutical formulation; polyethylene glycol in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation and titanium dioxide in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation. In a more preferred embodiment of the pharmaceutical formulations object of the present invention, the pharmaceutical formulation comprises: a pharmaceutical composition according to any of the modalities set forth above, coated with a coating which in turn comprises: hydroxypropylmethylcellulose in an amount of about 2 , 20 to 2.40% by weight of said coated pharmaceutical formulation; polyethylene glycol in an amount of about 0.20 to 0.24% by weight of said coated pharmaceutical formulation and titanium dioxide in an amount of about 0.30 to 0.50% by weight of said coated pharmaceutical formulation.

A further object of the present invention is a method of preparing the solid pharmaceutical compositions in unit dosage form for oral administration of the present invention, comprising: a) dry-mixing ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 30 to 37% by weight of said dosage form, with at least one diluent in an amount of about 55 to 65% by weight of said dosage form; at least one disintegrating agent in an amount of about 0.5 to 1.5% by weight of said dosage form; at least one lubricant in an amount of about 4.5 to 5.5% by weight of said dosage form; and b) subjecting the mixture thus obtained to a direct compression process and obtaining a unit dosage form for oral administration. In a preferred embodiment of the method of preparation of the present invention, the method comprises: a) dry-mixing ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 32 to 35% by weight of said dosage form with; at least one diluent in an amount of about 57 to 62% by weight of said dosage form; at least one disintegrating agent in an amount of about 0.7 to 1.2% by weight of said dosage form; at least one lubricant in an amount of about 4.7 to 5.2% by weight of said dosage form; and b) subjecting the obtained mixture to a direct compression process and obtaining a unit dosage form for oral administration. In an even more preferred embodiment of the method of preparation of the present invention, the method comprises: a) dry-mixing ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 34% by weight of said dosage form with; at least one diluent in an amount of about 60% by weight of said dosage form; at least one disintegrating agent in an amount of about 1% by weight of said dosage form; at least one lubricant in an amount of about 5% by weight of said dosage form; and b) subjecting the obtained mixture to a direct compression process and obtaining a unit dosage form for oral administration. In the most preferred embodiment the unit dosage form obtained by the method of preparation of the present invention is a tablet. In preferred embodiments of the method of the present invention, ibandronic acid is present in the form of its monohydrated monosodium salt. The diluent used in the method of preparation of the compositions of the present invention can be selected from any of those normally used in the pharmaceutical industry and is not restricted by any particular condition. In preferred embodiments of the invention, the at least one diluent is selected from the group of microcrystalline cellulose, preferably silicified, cellulose gel, microfine cellulose, cellulose powder or crystalline cellulose. Lactose for direct compression, anhydrous lactose for direct compression, hydrated lactose for direct compression, Cellactose 80® (co-precipitated microcrystalline cellulose and lactose), Tabletose 80® (lactose for direct compression), agglomerated lactose, mannitol, calcium dibasic phosphate can also be used dihydrate, calcium sulfate dihydrate and mixtures thereof. Silicified microcrystalline cellulose is preferred. Similarly, the disintegrating agent used in the method of preparing the compositions of the present invention can be selected from any of those normally used in the pharmaceutical industry and is not restricted by any particular condition. In preferred embodiments of the method of the present invention, the at least one disintegrant is selected from cross-linked sodium carboxymethylcellulose, Sodium starch glycolate, cross-linked povidone and polyvinylpolypyrrolidone and mixtures thereof. Sodium carboxymethylcellulose crosslinked is preferred.

Likewise, the lubricating agent used in the method of preparing the compositions of the present invention can be selected from any of those normally used in the pharmaceutical industry and is not restricted by any particular condition. In preferred embodiments of the method of the present invention, the lubricating agents are selected from sodium stearyl fumarate, talc and hydrogenated vegetable oil, such as for example the product marketed under the trademark Lubritab ® (hydrogenated vegetable oil) and mixtures thereof. Yet another additional object of the present invention is a process for preparing a pharmaceutical formulation comprising any of the preferred pharmaceutical compositions set forth above, wherein the process comprises: a step of spraying said pharmaceutical dosage forms with a solution of the pharmaceutical coating acceptable and a drying step of said pharmaceutical dosage forms coated with said pharmaceutically acceptable coating solution. The coating and coating compositions and agents used in the method of preparing the formulations of the present invention can be selected from any of those normally used in the pharmaceutical industry and is not restricted by any particular condition. In preferred embodiments of the method of preparing the formulations of the present invention, the coating or coating composition is selected from: methacrylic acid derivatives in an amount of about 1 to 4% by weight of said coated pharmaceutical formulation; diethyl phthalate in an amount of about 0.05 to 1% by weight of said formulation coated pharmaceutical and talc in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation, or hydroxyethylcellulose in an amount of about 1 to 4% by weight of said coated pharmaceutical formulation; triacetin in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation and magnesium carbonate in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation. In an even more preferred form of this further object of the present invention, the process for preparing a pharmaceutical formulation comprises applying a pharmaceutically acceptable coating which in turn comprises: hydroxypropylmethylcellulose in an amount of about 1 to 4% by weight of said formulation coated pharmaceutical; polyethylene glycol in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation; titanium dioxide in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation; and optionally talc in an amount of about 0.05 to 1% by weight of said pharmaceutical formulation. In the most preferred form of this further object of the present invention, the process of preparing a pharmaceutical formulation comprises applying a pharmaceutically acceptable coating which in turn comprises: hydroxypropylmethylcellulose in an amount of about 2.20 to 2.40% by weight of said coated pharmaceutical formulation; polyethylene glycol in an amount of about 0.20 to 0.24% by weight of said coated pharmaceutical formulation; Y titanium dioxide in an amount of about 0.30 to 0.50% by weight of said coated pharmaceutical formulation. EXAMPLES The invention will be illustrated below, in greater detail, by means of the following examples of embodiment, which in no way should be construed as limiting the scope of the invention.

Example 1: Coated tablets containing 150 mg of active ingredient., 79 g of ibandronate monosodium monohydrate and 298.80 g of microcrystalline cellulose. Both components are introduced in a mixer and processed until a homogeneous mixture is obtained. On the other hand, 4.98 g of cross-linked sodium carboxymethyl cellulose are sieved, loaded in the mixer together with the previously mixed components and processed until a homogeneous mixture is obtained. On the other hand, 9.96 g of sodium stearyl fumarate are sieved and 5, 51 g of talc are loaded in the mixer together with the previously mixed components and processed until a homogeneous mixture is obtained. 9.96 g of hydrogenated vegetable oil are sieved and added to the mixer with the remaining mixed components. It is processed until a homogeneous mixture is obtained. Next, the obtained mixture is compressed in a rotary tablet, obtaining 1000 base tablets. On the other hand, a coating suspension is prepared by mixing 12.00 g of hydroxypropylmethylcellulose, 1.20 g of polyethylene glycol 6000 and 2.00 g of titanium dioxide, in purified water and ethyl alcohol. The coating suspension is then applied by spraying on the base tablet obtained in the compression step and allowed to dry, obtaining 1000 coated tablets of a total core weight of 498 mg and a total weight of coated tablet of 513.20 mg containing an equivalent of 150 mg of free ibandronic acid, with the following composition: Nucleus (percentages by weight based on the total weight of the nucleus) Ibandronate monosodium monohydrate 168.79 mg = 33.89% by weight Silicified microcrystalline cellulose 298.80 mg = 60.00% by weight Croscarmellose sodium 4.98 mg = 1.00% by weight Talc 5.51 mg = 1.11% by weight Hydrogenated vegetable oil 9.96 mg = 2.00% by weight Sodium stearyl fumarate 9.96 mg = 2.00% by weight Coverage (percentages by weight based on the total weight of the coated tablet) Polyethylene glycol 6000 1.20 mg = 0.23% by weight Hydroxypropylmethylcellulose 12.00 mg = 2.34% by weight Titanium dioxide 2.00 mg = 0.39% by weight Example 2: Coated tablets containing 100 mg of active ingredient In a similar manner to that of Example 1, 112.53 g of ibandronate monosodium monohydrate and 199.20 g of silicified microcrystalline cellulose are screened and mixed. On the other hand, 3.32 g of cross-linked sodium carboxymethyl cellulose are sieved, loaded in the mixer together with the previously mixed components and processed until a homogeneous mixture is obtained. 6.64 g of sodium stearyl fumarate and , 67 g of talc, previously sieved and mixed until homogeneous. Subsequently, 6.64 g of hydrogenated vegetable oil are sieved and added to the obtained mixture, mixing again until homogeneity. The resulting mixture is compressed in a rotary tablet to obtain 1000 base tablets, which are spray coated with a coating suspension.

Said coating suspension is obtained by suspending 7.70 g of hydroxypropylmethyl cellulose, 0.77 g of polyethylene glycol 6000 and 1.49 g of titanium dioxide in purified water and ethyl alcohol. After drying, 1000 coated tablets of a total core weight of 332.00 mg and a total weight of coated tablet of 341, 96 mg containing an equivalent of 100 mg of free ibandronic acid are obtained, with the following composition: Core ( percentages by weight based on the total weight of the nucleus) Ibandronate monosodium monohydrate 112.53 mg = 33.89% by weight silicified microcrystalline cellulose 199.20 mg = 60.00% by weight Croscarmellose sodium 3.32 mg = 1.00% by weight Talcum 3.67 mg = 1, 11% by weight Hydrogenated vegetable oil 6.64 mg = 2.00% by weight Sodium stearyl fumarate 6.64 mg = 2.00% by weight Coverage (percentages by weight based on the total weight of the coated tablet) Polyethylene glycol 6000 0.77 mg = 0.22% by weight Hydroxypropylmethylcellulose 7.70 mg = 2.25% by weight Titanium dioxide 1.49 mg = 0.43% by weight Dissolution properties of the compositions of the present invention The excellent dissolution properties of the formulations of the present invention are demonstrated by a comparative dissolution test. For this purpose, the percentage of active principle dissolved as a function of time was evaluated, comparing the composition of Example 1 of the present invention with a commercially available product under the trademark BONIVA® tablets. At the end of this trial a dissolution system was used consisting of:? a type II device according to the US Pharmacopoeia (pallets), ? medium: distilled water? Temperature: 37 ° C ± 0.5 ° C? volume: 900 mi? Speed: 50 rpm? sample time: 15, 30, 45 and 60 minutes.

The values obtained are summarized in Table I below and are illustrated in the graph of Figure 1, indicating in the ordinates the dissolution percentage and in the abscissa the time elapsed since the beginning of the test.

Table I From the results of the preceding table and more clearly in the graph of Figure 1, it can be seen that the compositions of the present invention provide a better dissolution profile of the active principle, releasing it more quickly, in comparison with a commercially available product obtained by wet granulation. This is explained from the pharmacotechnical point of view by the immediate release and therefore the exposure of the crystals to the dissolution medium. In the technique of Direct Compression does not exist an entity called granule like the one existing in the Granulation process. Said granules must previously disintegrate to expose the active principle to the dissolution medium; in Direct Compression, once the tablet has disintegrated, the exposed entities are the crystals of the active principle. The product of the invention allows a correct swallowing without rapid disintegration in the oral cavity but obtaining a fast dissolution speed in an aqueous medium of greater volume. It can also be seen that in later phases the formulations of the present invention perform similarly to those of the commercial product.

This demonstrates that, unexpectedly, through the compositions of the present invention based on a much simpler and safer production technology, better results can be obtained regarding the release and disposition of ibandronate monosodium monohydrate than those obtained with commercially known products. available, with the consequent economy of resources.

Claims (1)

1. CLAIMS A solid pharmaceutical composition in unit dosage form for oral administration, characterized in that it comprises formulations by direct compression: ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 30 to 37% by weight of said dosage form; at least one diluent in an amount of about 55 to 65% by weight of said dosage form; at least one disintegrating agent in an amount of about 0.5 to 1.5% by weight of said dosage form; and at least one lubricant in an amount of about 4.5 to 5.5% by weight of said dosage form. A pharmaceutical composition according to claim 1, characterized in that it comprises: ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 32 to 35% by weight of said dosage form; at least one diluent in an amount of about 57 to 62% by weight of said dosage form; at least one disintegrating agent in an amount of about 0.7 to 1.2% by weight of said dosage form; Y at least one lubricant in an amount of about 4.7 to 5.2% by weight of said dosage form. A pharmaceutical composition according to claim 1 or 2, characterized in that it comprises: ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 34% by weight of said dosage form; at least one diluent in an amount of about 60% by weight of said dosage form; at least one disintegrating agent in an amount of about 1% by weight of said dosage form; and at least one lubricant in an amount of about 5% by weight of said dosage form. A pharmaceutical composition according to any of the preceding claims, characterized in that the ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof is ibandronate monosodium monohydrate. A pharmaceutical composition according to any of the preceding claims, characterized in that the at least one diluent is selected from the group of microcrystalline cellulose, preferably silicified, cellulose gel, crystalline cellulose, microfine cellulose, cellulose powder, lactose for direct compression, lactose anhydrous for direct compression, hydrated lactose for direct compression, co-precipitated microcrystalline cellulose and lactose, agglomerated lactose, mannitol, calcium dibasic phosphate dihydrate and calcium sulfate dihydrate and mixtures thereof. A pharmaceutical composition according to any of the preceding claims, characterized in that the at least one disintegrant is selected from the group of cross-linked sodium carboxymethyl cellulose, sodium starch glycolate, cross-linked povidone and polyvinylpolypyrrolidone and mixtures thereof. A pharmaceutical composition according to any of the preceding claims, characterized in that the at least one lubricant it is selected from sodium stearyl fumarate, talc and hydrogenated vegetable oil and mixtures thereof. 8. A pharmaceutical composition according to any of the preceding claims, characterized in that it comprises, formulated by direct compression: ibandronate monosodium monohydrate in an amount of about 33.89% by weight of said dosage form; silicified microcrystalline cellulose in an amount of about 60.00% by weight of said dosage form; sodium carboxymethylcellulose crosslinked in an amount of about 1.00% by weight of said dosage form; talc in an amount of about 1.11% by weight of said dosage form; hydrogenated vegetable oil in an amount of about 2.00% by weight of said dosage form; and sodium stearyl fumarate in an amount of about 2.00% by weight of said dosage form. 9. A pharmaceutical composition according to any of the preceding claims, characterized in that it has the form of a compressed tablet. 10. A pharmaceutical formulation characterized in that it comprises a composition according to any of the preceding claims in unit dosage form coated with a pharmaceutically acceptable coating. 11. A pharmaceutical formulation according to claim 10, characterized in that the coating comprises: hydroxypropylmethylcellulose in an amount of about 1 to 4% by weight of said coated pharmaceutical formulation; polyethylene glycol in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation; titanium dioxide in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation; and optionally talc in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation. 12. A pharmaceutical formulation according to any of claims 10 or 11, characterized in that the coating comprises: hydroxypropylmethylcellulose in an amount of about 2.20 to 2.40% by weight of said coated pharmaceutical formulation; polyethylene glycol in an amount of about 0.20 to 0.24% by weight of said coated pharmaceutical formulation; and titanium dioxide in an amount of about 0.30 to 0.50% by weight of said coated pharmaceutical formulation. 13. A pharmaceutical formulation according to any of claims 10 to 12, characterized in that the coating comprises: hydroxypropylmethylcellulose in an amount of about 2.34% by weight of said coated pharmaceutical formulation; polyethylene glycol in an amount of about 0.23% by weight of said coated pharmaceutical formulation; and titanium dioxide in an amount of about 0.39% by weight of said coated pharmaceutical formulation. 14. A pharmaceutical formulation according to any of claims 10 to 12, characterized in that the coating comprises: hydroxypropylmethylcellulose in an amount of about 2.25% by weight of said coated pharmaceutical formulation; polyethylene glycol in an amount of about 0.22% by weight of said coated pharmaceutical formulation; and titanium dioxide in an amount of about 0.43% by weight of said coated pharmaceutical formulation. 15. A process for the preparation of a composition according to claim 1, characterized in that it comprises: a) dry-mixing ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 30 to 37% by weight of said dosage form, with at least one diluent in an amount of about 55 to 65% by weight of said dosage form; at least one disintegrating agent in an amount of about 0.5 to 1.5% by weight of said dosage form; at least one lubricant in an amount of about 4.5 to 5.5% by weight of said dosage form; and b) subjecting the mixture thus obtained to a direct compression process and obtaining a unit dosage form for oral administration. 16. A process according to claim 15, characterized in that it comprises: a) dry-mixing ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 32 to 35% by weight of said dosage form; with at least one diluent in an amount of about 57 to 62% by weight of said dosage form; at least one disintegrating agent in an amount of about 0.7 to 1.2% by weight of said dosage form; at least one lubricant in an amount of about 4.7 to 5.2% by weight of said dosage form; and b) subjecting the obtained mixture to a direct compression process and obtaining a unit dosage form for oral administration. 17. A process according to claim 15 or 16, characterized in that it comprises: a) dry-mixing an ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof in an amount of about 34% by weight of said dosage form; with at least one diluent in an amount of about 60% by weight of said dosage form; at least one disintegrating agent in an amount of about 1% by weight of said dosage form; at least one lubricant in an amount of about 5% by weight of said dosage form; and b) subjecting the obtained mixture to a direct compression process and obtaining a unit dosage form for oral administration. 18. A process according to any of claims 15 to 17, characterized in that the ibandronic acid or a pharmaceutically acceptable salt or hydrate thereof is ibandronate monosodium monohydrate. A process according to any of claims 15 to 18, characterized in that the at least one diluent is selected from the group of microcrystalline cellulose, preferably silicified, cellulose gel, crystalline cellulose, microfine cellulose, cellulose powder, lactose for direct compression, lactose anhydrous for direct compression, hydrated lactose for direct compression, co-precipitated microcrystalline cellulose and lactose, agglomerated lactose, mannitol, calcium dihydrate phosphate dihydrate and calcium sulfate dihydrate. 20. A process according to any of claims 15 to 19, characterized in that the at least one disintegrant is selected from the group of cross-linked sodium carboxymethylcellulose, sodium starch glycolate, cross-linked povidone, polyvinylpolypyrrolidone and mixtures thereof. 21. A process according to any of claims 15 to 20, characterized in that the at least one lubricant is selected from sodium stearyl fumarate, talc and hydrogenated vegetable oil and mixtures thereof. 22. A process according to any of claims 15 to 21, characterized in that it comprises: a) dry mixing of ibandronate monosodium monohydrate in an amount of about 33.89% by weight of said dosage form; with silicified microcrystalline cellulose in an amount of about 60.00% by weight of said dosage form; sodium carboxymethylcellulose crosslinked in an amount of about 1.00% by weight of said dosage form; talc in an amount of about 1.11% by weight of said dosage form; hydrogenated vegetable oil in an amount of about 2.00% by weight of said dosage form; sodium stearyl fumarate in an amount of about 2.00% by weight of said dosage form; and b) subjecting the obtained mixture to a direct compression process and obtaining a unit dosage form for oral administration. 23. A process for preparing a pharmaceutical formulation according to claim 10, comprising a pharmaceutical composition according to any of claims 1 to 9, characterized in that said pharmaceutical dosage form is subjected to a coating process with a pharmaceutically acceptable coating. 24. A process for preparing a pharmaceutical formulation according to claim 23, characterized in that said coating process comprises a step of spraying said pharmaceutical dosage forms with a pharmaceutically acceptable coating solution and a drying step of said dosage forms. pharmaceutical coated with said pharmaceutically acceptable coating solution. 25. A process for preparing a pharmaceutical formulation according to claim 23 or 24, characterized in that said pharmaceutically acceptable coating comprises: hydroxypropylmethylcellulose in an amount of about 1 to 4% by weight of said coated pharmaceutical formulation; polyethylene glycol in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation; titanium dioxide in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation; Y optionally talc in an amount of about 0.05 to 1% by weight of said coated pharmaceutical formulation. 26. A process for preparing a pharmaceutical formulation according to claim 23 to 25, characterized in that said pharmaceutically acceptable coating comprises: hydroxypropylmethylcellulose in an amount of about 2.20 to 2.40% by weight of said coated pharmaceutical formulation; polyethylene glycol in an amount of about 0.20 to 0.24% by weight of said coated pharmaceutical formulation; Y titanium dioxide in an amount of about 0.30 to 0.50% by weight of said coated pharmaceutical formulation. 27. A process for preparing a pharmaceutical formulation according to claim 23 to 26, characterized in that said pharmaceutically acceptable coating comprises: hydroxypropylmethylcellulose in an amount of about 2.34% by weight of said coated pharmaceutical formulation; polyethylene glycol in an amount of about 0.23% by weight of said coated pharmaceutical formulation; and titanium dioxide in an amount of about 0.39% by weight of said coated pharmaceutical formulation. 28. A process for preparing a pharmaceutical formulation according to claim 23 to 26, characterized in that said pharmaceutically acceptable coating comprises: hydroxypropylmethylcellulose in an amount of about 2.25% by weight of said coated pharmaceutical formulation; polyethylene glycol in an amount of about 0.22% by weight of said coated pharmaceutical formulation; and titanium dioxide in an amount of about 0.43% by weight of said coated pharmaceutical formulation.