DESC:FIELD OF INVENTION

The present invention relates to pharmaceutical composition of orally disintegrating strips. It relates more specifically strips containing microcrystalline hydroxyapatite complex (MCHC).

BACKGROUND OF THE INVENTION

This invention relates to dietary supplements. More particularly, this invention relates to compositions and methods for promoting healthy bone structure.

Osteoporosis is a common metabolic bone disease that leads to the gradual loss of mineralized bone from the skeletal mass. This is due in part to an imbalance in the rates of cell-mediated bone deposition and resorption due to the actions of osteoblasts and osteoclasts in the bone matrix. Bone mineral is in a constant state of destruction and repair referred to as “remodeling,” and maintenance of bone density over time is believed to require a precise balance after menopause or during the course of certain disease states. Bone resorption, when exceeding bone formation, can lead to bone fractures resulting from minimal trauma. Unfortunately, there are no symptoms preceding fractures. A common cause of osteoporosis is the decrease in estrogen production following menopause that leads to an increase in bone resorption. Conventional methods to counter bone resorption in women include estrogen therapy and calcium supplementation. Long-term treatment with estrogen has been the only method correlated to significant protection from bone loss in postmenopausal women. See Agnusdei D, Bufalino L.

Adequate calcium ingestion and absorption is crucial for the maintenance of bone mass. Research indicates that the presence of other food components with elemental calcium greatly increases absorption. Ossein-mineral-compound prepared from calf bone powder has been shown to increase calcium absorption (as compared to synthetic microcrystalline hydroxyapatite) and contains proteins that are mitogenic for bone cells in vitro. See Stepan J J, Mohan S, Jennings J C, et al., Quantitation of growth factors in ossein-mineral-compound, Life Sciences 1991;49:79-84. Microcrystalline hydroxyapatite from raw whole bone also contains the minerals phosphorus, magnesium, fluoride, zinc, silicon, manganese, copper, and other trace minerals that are physiologically involved in bone formation and metabolism. Trace minerals have catalytic functions (important as cofactors for the proper functioning of specific enzymes) in organic bone matrix that are crucial for the normal development and maintenance of skeletal tissue. See Strause et al., The role of trace elements in bone metabolism, Nutritional Aspects of Osteoporosis, New York: Raven Press; 1991(Strause, 1991).

US Patent No.6447809 discloses the dietary supplement for benefitting human bone health includes a calcium source, a source of vitamin D activity, and an osteoblast stimulant.

Oral dissolving films are gaining interest as an alternative of fast dissolving tablets. The films are designed to dissolve upon contact with a wet surface, such as the tongue, within a few seconds, meaning the consumer can take the product without need for additional liquid. This convenience provides both a marketing advantage and increased patient compliance. As the drug is directly absorbed into systemic circulation, degradation in gastrointestinal tract and first pass effect can be avoided. These points make this formulation most popular and acceptable among pediatric and geriatric patients and patients with fear of choking.

The oral route is one of the most preferred routes of drug administration as it is more convenient, cost effective, and ease of administration lead to high level of patient compliance. The oral route is problematic because of the swallowing difficulty for pediatric and geriatric patients who have fear of choking. Patient convenience and compliance oriented research has resulted in bringing out safer and newer drug delivery systems. Recently, fast dissolving drug delivery systems have started gaining popularity and acceptance as one such example with increased consumer choice, for the reason of rapid disintegration or dissolution, self-administration even without water or chewing as to overcome swallowing difficulties associated with tablets and capsules for pediatric and geriatric patients. The surface of buccal cavity comprises of stratified squamous epithelium which is essentially separated from the underlying tissue of lamina propria and submucosa by an undulating basement membrane. It is interesting to note that the permeability of buccal mucosa is approximately 4-4,000 times greater than that of the skin, but less than that of the intestine.

An ideal fast dissolving delivery system should have the following properties: High stability, transportability, ease of handling and administration, no special packaging material or processing requirements, no water necessary for application, and a pleasant taste. Therefore, they are very suitable for pediatric and geriatric patients; bedridden patients; or patients suffering from dysphagia, parkinson's disease, Mucositis, or vomiting. Formulation of fast dissolving buccal film involves material such as strip-forming polymers, plasticizers, active pharmaceutical ingredient, sweetening agents, saliva stimulating agent, flavoring agents, coloring agents, stabilizing and thickening agents, permeation enhancers, and superdisintegrants.

However, there exists a need to develop pharmaceutical composition of orally disintegrating strips. It relates more specifically strips containing microcrystalline hydroxyapatite complex as calcium supplement.

SUMMARY OF INVENTION

In one object, the present invention provides herein, pharmaceutical composition of orally disintegrating strips consisting essentially of a therapeutically effective amount of microcrystalline hydroxyapatite complex and an excipient that facilitates oral administration.

In another objective, the present invention provides pharmaceutical composition of orally disintegrating strips which is comprising microcrystalline hydroxyapatite complex, sweetening agent, binder, flavor, film forming agent, humectant and purified water.

DETAILED DESCRIPTION OF THE INVENTION

In one object, the present invention provides herein, pharmaceutical composition of orally disintegrating strips consisting essentially of a therapeutically effective amount of microcrystalline hydroxyapatite complex and an excipient that facilitates oral administration.

In a preferred embodiment, the pharmaceutical composition of the invention is orally disintegrating strips.

In a most preferred embodiment, the pharmaceutical orally disintegrating strips composition comprises microcrystalline hydroxyapatite complex and pharmaceutically acceptable excipients.

Microcrystalline hydroxyapatite complex is preferably used in pharmaceutical composition of orally disintegrating strips about 45% to about 65% based on total weight of the orally disintegrating strip composition.

In another embodiment, the present invention provides pharmaceutical composition of orally disintegrating strips which is comprising microcrystalline hydroxyapatite complex, sweetening agent, binder, flavor, film forming agent, humectant and purified water.

In yet another embodiment, the microcrystalline hydroxyapatite complex pharmaceutical orally disintegrating strip composition of the present invention is characterized in that the raw material components of the microcrystalline hydroxyapatite complex orally disintegrating strip include by total weight of composition contains microcrystalline hydroxyapatite complex 45% - 65%, sweeting agent 0.1% - 1.5%, binder 1% - 10%, flavor 1% - 10%, film forming agent 15% - 35% humectant 1% - 15% and sufficient quantity of purified water.

Examples of the sweeting agent is selected from the group consisting of sucrose, dextrose, fructose, glucose, liquid glucose, maltose saccharin, cyclamate, aspartame, acesulpham K, sucralose, alitame, neotame and mixtures thereof. Preferably, the sweeting agent is selected from sucralose. Sweeting agent preferably used in the pharmaceutical orally disintegrating strips composition of about 0.1% to about 1.5% based on the total weight of the composition. Most preferably, sweeting agent is used in the composition of about 0.5% to about 1% based on total weight of the composition

Examples of the binder is selected from the group consisting of hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), hydroxyethylcellulose (HEC), starch (e.g., corn starch or potato starch), pregelatinized starch, silicified microcrystalline cellulose, povidone, cellulose derivatives (e.g., methylcellulose and sodium carboxymethylcellulose), gelatin, polyethylene glycol, sodium alginate and mixtures thereof. Preferably, the binder is selected from pregelatinized starch. Binder preferably used in the pharmaceutical orally disintegrating strips composition of about 1% to about 10% based on the total weight of the composition. Most preferably, binder is used in the composition of about 3% to about 8% based on total weight of the composition.

Examples of the flavor agent is selected from the group consisting of peppermint flavour, cooling flavor (menthol), flavor oils, flavoring aromatic oil, peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil thyme oil, oil of bitter almonds. Flavoring agents include, vanilla, solid choco flavor, citrus oils, fruit essences, and any combinations thereof. Preferably, the flavor agent is selected from vanilla. Flavor agent preferably used in the pharmaceutical orally disintegrating strips composition of about 1% to about 10% based on the total weight of the composition. Most preferably, flavoring agent is used in the composition of about 3% to about 8% based on total weight of the composition.

Examples of the film forming agent is selected from the group consisting of hydroxyalkyl methyl cellulose, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose, and mixtures thereof. Film forming agent preferably used in the pharmaceutical orally disintegrating strips composition of about 15% to about 35% based on the total weight of the composition. Most preferably, film forming agent is used in the composition of about 20% to about 30% based on total weight of the composition.

Examples of the humectant is selected from the group consisting of glycerol, sorbitol, polyethylene glycol, propylene glycol, xylitol, and mixtures thereof. Humectant preferably used in the pharmaceutical orally disintegrating strips composition of about 1% to about 15% based on the total weight of the composition. Most preferably, humectant is used in the composition of about 5% to about 10% based on total weight of the composition.

The following examples are provided to illustrate the present invention. It is understood, however, that the invention is not limited to the specific conditions or details described in the examples below. The examples should not be construed as limiting the invention as the examples merely provide specific methodology useful in the understanding and practice of the invention and its various aspects. While certain preferred and alternative embodiments of the invention have been set forth for purposes of disclosing the invention, modification to the disclosed embodiments can occur to those who are skilled in the art.

Examples 1:

Orally disintegrating strips with the following composition is prepared.

S. No. Ingredients %W/W
1 Micro-Crystalline Hydroxyapatite Complex (MCHC) 45% - 65%
2 Sucralose 0.1% - 1.5%
3 Pregelatinized Starch 1% - 10%
4 Vanilla Flavor 1% - 10%
5 Hydroxypropyl Methyl Cellulose (HPMC) 15% - 35%
6 Glycerol 1% - 15%
7 Purified Water Q.S.
Total 100.00

Each 165mg of MCHC contains 33mg of calcium and 15mg of phosphorus

Manufacturing Process:

Preparation of HPMC Base:

Weighed quantity of hot Purified Water was taken in a beaker and slowly HPMC powder was added to it and kept under continuous stirring. Then Purified Water was added to it, stirred for 10 minutes and kept aside for overnight to remove air bubbles.

Formulation:

1. Weighed quantity of Purified Water was taken in a beaker and MCHC was added to it, stirred manually for 1 minute and sonicated for 5 minutes.

2. Weighed quantity of Vanilla Flavor was added to Step No. 1 and stirred it for 2 minutes.
3. Weighed quantity of Sucralose was added to Step No. 2 and stirred 2 minutes.
4. Weighed quantity of Pregelatinized Starch was added to Step No. 3 and sonicated it for 5 minutes.
5. Weighed quantity of Hydroxypropyl Methyl Cellulose was added to Step No. 4 and stirred it for 2 minutes.
6. Weighed quantity of Glycerol was added to Step No. 5 and stirred for 5 minutes.
7. Above formulation was packed & kept overnight to get bubble free slurry.
8. Slurry was layered & dried to get oral disintegrating strip.
,CLAIMS:We Claim

1. A pharmaceutical composition of orally disintegrating strips consisting essentially of a therapeutically effective amount of microcrystalline hydroxyapatite complex and an excipient that facilitates oral administration.

2. The pharmaceutical composition according to claim 1, wherein excipients are selected from group consisting of sweetening agents, binder, flavor, film forming agent, humectant and purified water.

3. The pharmaceutical composition according to claim 2, wherein the composition comprises of about 0.1% to about 1.5% of sweetening agents based on the total weight of the composition.

4. The pharmaceutical composition according to claim 2, wherein the composition comprises of about 1% to about 10% of binder based on the total weight of the composition.

5. The pharmaceutical composition according to claim 2, wherein the composition comprises of about 20% to about 30% of film forming agent based on the total weight of the composition.

6. The pharmaceutical composition according to claim 2, wherein the film forming agents are selected from the group consisting of hydroxyalkyl methyl cellulose, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose, hydroxyethyl cellulose, methyl cellulose, carboxymethyl cellulose, and mixtures thereof.

7. The pharmaceutical composition according to claim 1, wherein the composition comprises of about 45% to about 65% microcrystalline hydroxyapatite complex based on the total weight of the composition.