Claims:I/We Claim:

1. A stable sublingual composition with a fast disintegration time, comprising:

(a) nitroglycerine;
(b) lactose monohydrate;
(c) povidone;
(d) crospovidone;
(e) colloidal silicon dioxide and
(f) magnesium stearate.

2. The stable sublingual composition of claim 1, wherein a quantity of the nitroglycerine is prepared by mixing 10% nitroglycerin in lactose.

3. The stable sublingual composition of claim 1, wherein a quantity of the nitroglycerin present approximately by 15% by wt, wherein a quantity of the lactose monohydrate ranges from 76.0-78.3% by wt., wherein a quantity of the povidone ranges from 1.5-2.5% by wt., wherein a quantity of the crospovidone ranges from 3.0-4.0% by wt., wherein a quantity of the colloidal silicon dioxide ranges from 1.5-2.5% by wt., wherein a quantity of the magnesium stearate ranges from 0.5-1.0% by wt.

4. The stable sublingual composition of claim 1, wherein the composition is formulated in a tablet dosage form using a direct compression technique.

5. The stable sublingual composition of claim 1, wherein the fast disintegration time is less than 25 seconds.

6. A stable sublingual composition with a fast disintegration time, comprising:
(a) 15% by wt. of lactose that comprises 10% nitroglycerin;
(b) 76.0-78.3% by wt. of lactose monohydrate;
(c) 1.5-2.5 % by wt. of povidone;
(d) 3.0-4.0% by wt. of crospovidone;
(e) 1.5-2.5% by wt. of colloidal silicon dioxide; and
(f) 0.5-1.0% by wt. of magnesium stearate.

7. The stable sublingual composition of claim 6, wherein the composition is formulated in a tablet dosage form using direct compression technique.

8. The stable sublingual composition of claim 6, wherein the fast disintegration time is less than 25 seconds.

9. A process of preparation of a stable sublingual composition with fast disintegration time, comprising:
mixing (a) 15% by wt. of lactose that comprises 10% nitroglycerin, (b) 76.0-78.3% by wt. of lactose monohydrate, (c) 1.5-2.5% by wt. of povidone, (d) 3.0-4.0% by wt. of crospovidone, (e) 1.5-2.5% by wt. of colloidal silicon dioxide, and (f) 0.5-1.0% by wt. of magnesium stearate and
compressing the stable sublingual composition by direct compression technique to obtain the stable sublingual tablets with fast disintegration time.

10. The process of claim 9, wherein the fast disintegration time is less than 25 seconds. , Description:BACKGROUND
Technical Field
[0001] The embodiments herein generally relate to pharmaceutical composition, and, more particularly, to stable nitroglycerin containing pharmaceutical compositions.

Description of the Related Art
[0002] Glyceryl tri nitrate, hereinafter referred to as nitroglycerin, is a liquid at normal temperatures. Nitroglycerin has a vapor pressure of about 0.00026 m.m. at 20° C. Moreover, nitroglycerin is a violent explosive which must be handled with great care. It was found a long time ago that a safe and effective preparation containing nitroglycerin could be prepared by titrating 1 part of nitroglycerin and 9 parts of beta-lactose. This 10 percent nitroglycerin titration can then be further diluted with other agents for the preparation of tablets of nitroglycerin containing varying amounts of the drug. Consequently, it has been conventional in the pharmaceutical art to supply the trade with at least four different strengths of nitroglycerin tablets. These are: 1/400, 1/200, 1/150, and 1/100 grains of nitroglycerin per tablet. Conventionally, nitroglycerin has been formed into what are called molded tablets which contain soluble ingredients and can be placed under the tongue to achieve a rapid onset of the action of the drug.
[0003] Recently, it has been found that tablets of nitroglycerin, when packaged in a container wherein bulk tablets are in contact with one another, do not maintain a uniform potency with age. However, this lack of uniformity of potency does not indicate a loss of the nitroglycerin but rather the migration of the nitroglycerin from one tablet to another when such tablets are in random orientation in contact with each other. It has been found that over a period of a year as much as 20 percent or more of the nitroglycerin in a tablet could be lost by that tablet through contact with another tablet of like composition. Conversely, another tablet could gain as much or more potency through the absorption of migrating nitroglycerin. The exact cause of this phenomenon is not known. In fact, it is safe to store nitroglycerin tablets in glass containers. Various attempts have been made to improve the molded tablet formulation to assure better stability. In 1973, Parke-Davis & Co. added polyethylene glycol 3350 to molded tablet formulations. Though this additive reduced the migration and loss of nitroglycerin to some extent, the content uniformity range is increased upon storage.
[0004] From this time, a large number of stabilizing agents were explored and some were found to decrease the volatility of nitroglycerin in tablets. Among these were pregelantinized starch, microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP), and ß-cyclodextrin (BCD). M. David Richman, C. David Fox and Ralph F. Shangraw used microcrystalline cellulose for preparing tablets of glyceryl trinitrate using direct compression. The tablets showed slight loss (50%) of nitroglycerine over the commercial hypodermic tablets which lost up to 95 per cent. A compressed tablet was prepared using the combination of MCC & PVP and marketed by Warner Chilcott Laboratories as NitroPRN®. The tablet was far superior to the current molded tablets with respect to nitroglycerin migration and volatility. However, the high amount of water insoluble excipient (MCC) was not desirable since the tablet gave a less acceptable feel and slower disintegration under the tongue.
[0005] Several patents on the stabilization of nitroglycerin in tablets have been granted. U.S. Pat. No. 4,091,091 assigned to Eli Lilly and Co., discloses the usage water soluble PVP to improve the stability of molded nitroglycerin tablets. In this method, PVP is added from a solution and molded tablets are made by the traditional method. Another patent, U.S. Pat. No. 4,059,686 assigned to Nippon Kayaku, indicates that ß cyclodextrin as an effective stabilizing agent. However, a high degree of weight variation occurs and this attribute, coupled with inter-tablet migration of nitroglycerin in above mentioned methods. Another application, WO1999017766 assigned to Warner-Lambert Company, describes a stable nitroglycerin containing pharmaceutical composition, preferably a tablet which is prepared by direct compression technology. The stable tablets are characterized by a decreased migration of nitroglycerin, decreased potency loss, excellent content uniformity when stored. These tablets use pregelatinized starch as disintegrant. Use of natural products like pregelantinized starch (used in the existed formulas in the market) may cause of microbiological growth in the long-term stage. As it is a natural product, it may get shortage of material at the time of commercialization. The lack of technical improvement relates to the complexity of the formulation with respect to selection of excipients and stabilizing agents which can be used to closely mimic the physical and chemical attributes of molded tablets and afford a significantly improved stability, and similar disintegration and bioavailability. However, as of now, significant improvements have not been made in marketed products.
[0006] As indicated above, there remains a need for a stable sublingual nitroglycerin tablet with a fast disintegration time.

SUMMARY
[0007] In view of a foregoing, in an aspect herein provides a stable sublingual composition with a fast disintegration time including (a) nitroglycerine, (b) lactose monohydrate, (c) povidone, (d) crospovidone, (e) colloidal silicon dioxide and (f) magnesium stearate. In one embodiment, the stable sublingual composition includes a quantity of the nitroglycerine is prepared by mixing 10% nitroglycerin in lactose.
[0008] In another embodiment, the stable sublingual composition includes a quantity of the nitroglycerin present approximately by 15% by wt, a quantity of the lactose monohydrate ranges from 76.0-78.3% by wt., a quantity of the povidone ranges from 1.5-2.5% by wt., a quantity of the crospovidone ranges from 3.0-4.0% by wt., a quantity of the colloidal silicon dioxide ranges from 1.5-2.5% by wt., a quantity of the magnesium stearate ranges from 0.5-1.0% by wt.
[0009] In yet another embodiment, the stable sublingual composition is formulated in a tablet dosage form using a direct compression technique. In yet another embodiment, the fast disintegration time is less than 25 seconds.
[0010] In one aspect, a stable sublingual composition with a fast disintegration time including, (a) 15% by wt. of lactose having 10% nitroglycerin, (b) 76.0-78.3% by wt. of lactose monohydrate, (c) 1.5-2.5% by wt. of povidone, (d) 3.0-4.0% by wt. of crospovidone, (e) 1.5-2.5% by wt. of colloidal silicon dioxide, and (f) 0.5-1.0% by wt. of magnesium stearate. In one embodiment, the stable sublingual composition is formulated in a tablet dosage form using direct compression technique. In another embodiment, the fast disintegration time is less than 25 seconds.
[0011] In another aspect, a process of preparation of a stable sublingual composition with fast disintegration time, including, mixing (a) 15% by wt. of lactose having 10% nitroglycerin, (b) 76.0-78.3% by wt. of lactose monohydrate, (c) 1.5-2.5% by wt. of povidone, (d) 3.0-4.0% by wt. of crospovidone, (e) 1.5-2.5% by wt. of colloidal silicon dioxide, and (f) 0.5-1.0% by wt. of magnesium stearate and compressing the stable sublingual composition by direct compression technique to obtain the stable sublingual tablets with fast disintegration time.
[0012] These and other aspects of the embodiments herein will be better appreciated and understood when considered in conjunction with the following description and the accompanying drawings. It should be understood, however, that the following descriptions, while indicating preferred embodiments and numerous specific details thereof, are given by way of illustration and not of limitation. Many changes and modifications may be made within the scope of the embodiments herein without departing from the spirit thereof, and the embodiments herein include all such modifications.

BRIEF DESCRIPTION OF THE DRAWINGS

[0001] The embodiments herein will be better understood from the following detailed description with reference to the drawings, in which:
[0002] FIG. 1 is a table view that illustrates ingredients used for preparing a stable sublingual composition with fast disintegration time according to an embodiment herein; and
[0003] FIG. 2 is a flow diagram illustrating a process of preparing the stable sublingual composition with fast disintegration time using the quantities of ingredients of FIG. 1 according to an embodiment herein.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0004] The embodiments herein and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments that are illustrated in the accompanying drawings and detailed in the following description. Descriptions of well-known components and processing techniques are omitted so as to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
[0005] As mentioned, there remains a need for a stable sublingual nitroglycerin tablet with a fast disintegration time. The embodiments herein achieve this by preparing a stable sublingual composition with a fast disintegration time. Referring now to the drawings, and more particularly to FIG. 1 and FIG. 2, where similar reference characters denote corresponding features consistently throughout the figures, there are shown preferred embodiments.
Definitions:
[0006] The embodiment herein provides a sublingual composition comprising or consisting of a composition that is administered through under the tongue pharmacological route. The composition includes drugs that are diffused into the blood through tissues under the tongue.
[0007] By “fast disintegration time” we mean the time taken by the composition to disintegrate or dissolve is remarkably fast, within a few seconds. The composition disintegrates or dissolves within a few seconds in the saliva or mouth or in the oral cavity without the need for water.
[0008] FIG. 1 is a table view 100 that illustrates ingredients used for preparing a stable sublingual composition with fast disintegration time according to an embodiment herein. The table view 100 includes an ingredients field 102, and a quantity of the ingredients field 104. The ingredients field 102 includes the list of ingredients which are used to prepare a stable sublingual composition. The quantity of the ingredients field 104 includes a percentage of the ingredients which can be used to prepare the stable sublingual composition. For example, the stable sublingual composition with a fast disintegration time includes (a) nitroglycerine, (b) lactose monohydrate, (c) povidone, (d) crospovidone, (e) colloidal silicon dioxide and (f) magnesium stearate, in one embodiment.
[0009] In another embodiment, the stable sublingual composition with a fast disintegration time includes (a) a quantity of the nitroglycerin present approximately by 15% by wt, (b) a quantity of the lactose monohydrate ranges from 76.0-78.3% by wt., (c) a quantity of the povidone ranges from 1.5-2.5% by wt., (d) a quantity of the crospovidone ranges from 3.0-4.0% by wt., (e) a quantity of the colloidal silicon dioxide ranges from 1.5-2.5% by wt., and (f) a quantity of the magnesium stearate ranges from 0.5-1.0% by wt.
[0010] In one embodiment, the stable sublingual composition with a fast disintegration time includes a quantity of the nitroglycerine is prepared by mixing 10% nitroglycerin in lactose. In another embodiment, the stable sublingual composition with a fast disintegration time includes (a) 15% by wt. of lactose that comprises 10% nitroglycerin, (b) a quantity of the lactose monohydrate ranges from 76.0-78.3% by wt., (c) a quantity of the povidone ranges from 1.5-2.5% by wt., (d) a quantity of the crospovidone ranges from 3.0-4.0% by wt., (e) a quantity of the colloidal silicon dioxide ranges from 1.5-2.5% by wt., and (f) a quantity of the magnesium stearate ranges from 0.5-1.0% by wt.
[0011] In one embodiment, the stable sublingual composition with a fast disintegration time is formulated in a tablet dosage form using a direct compression technique. In one embodiment, the stable sublingual composition with a fast disintegration time less than 25 seconds.
[0012] FIG. 2 is a flow diagram 200 illustrating a process of preparing the stable sublingual composition with fast disintegration time using the quantities of ingredients of FIG. 1 according to an embodiment herein. At step 202, (a) 15% by wt. of lactose having 10% nitroglycerin, (b) 76.0-78.3% by wt. of lactose monohydrate, (c) 1.5-2.5% by wt. of povidone, (d) 3.0-4.0% by wt. of crospovidone, (e) 1.5-2.5% by wt. of colloidal silicon dioxide, and (f) 0.5-1.0% by wt. of magnesium stearate are mixed. At step 204, the stable sublingual composition is compressed by direct compression technique to obtain the stable sublingual tablets with fast disintegration time. In one embodiment, the stable sublingual composition with a fast disintegration time less than 25 seconds.
[0013] The stable sublingual composition has better stability and also faster disintegration time that is less than 25 seconds. This property is achieved by presence of super disintegrant “crospovidone” in the composition. Crospovidone is used as super disintegrating agent and will enhance the disintegrating rate (<25 sec) much faster than similar products like pre gelantinized starch, microcrystalline cellulose which are used in the existed formulas in the market (those disintegrating rate is < 30 seconds). The stability of nitroglycerin is achieved by the proper mixture of above mentioned components in a proposed percentage of weight. It is always better to have the fast disintegrating tablets in sublingual way of dosage form. The composition is completely based on the synthetic materials and can be produced as much as needed.
[0014] The foregoing description of the specific embodiments will so fully reveal the general nature of the embodiments herein that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. Therefore, while the embodiments herein have been described in terms of preferred embodiments, those skilled in the art will recognize that the embodiments herein can be practiced with modification within the spirit and scope of the appended claims.