Title of Invention

"process for preparing orally administrable pharmaceutical formulation comprising ephedrine hydrochloride"

Abstract

The present invention relates to a pharmaceutical formulation for oral administration through a soft gelatin capsule drug delivery device, wherein the said pharmaceutical formulation comprises essentially of Ephedrine HC1 as the active ingredient. The active pharmaceutical ingredient is embedded into an oily matrix, also the formulation comprises of an expectorant; a surfactant; a suspending agent; and a suspension medium. The said expectorant is guaifenesin, the surfactant; is lecithin, the suspending agent is yellow beeswax, and the suspension medium is soybean oil. The formulation comprises of about 25 mg by weight of Ephedrine HC1 in one instance and 12.5 mg by weight in another, about 200 mg by weight of guaifenesin, about 0.1-5.0 mg by weight of yellow beeswax, about 10-15 mg by weight of lecithin; and about 200-300 mg by weight of soybean oil. Also the invention is addressed at the process for preparing the formulation.

Full Text

PROCESS FOR PREPARING ORALLY ADMINISTRABLE PHARMACEUTICAL FORMULATION COMPRISING EPHEDRINE HYDROCHLORIDE Background of the Invention Field of the Invention This invention in general relates to process for producing orally administrable pharmaceutical formulations and in particular to an improved process for producing a pharmaceutical formulation containing Ephedrine hydrochloride and disposing the same into a soft gelatin capsule. Description of the Related Art Ephedrine hydrochloride is a drug that has serious potential for abuse. This is so because, Ephedrine can be extracted from various drug products containing Ephedrine hydrochloride and can be converted into amphetamines. Amphetamines have potentially lethal stimulant effects on the central nervous system and heart and it is therefore useful to minimize such abuse potential. Ephedrine HC1 is well known as a vasoconstrictor. Its use is therefore significant in symptomatic relief from congestion occurring in bronchial asthma. Ephedrine as a broncho-dilator has a slower onset but longer duration of action. Ephedrine provides temporary relief from shortness of breath, tightness of chest and wheezing in bronchial asthma. Pharmaceutical compositions comprising Ephedrine HC1 as its principal ingredient is known. U.S. Patent 5,858,371 to Singh, et al., describes a vasoconstrictor used, in the composition as Ephedrine. This disclosure is directed to a pharmaceutical composition for topical application. U.S. Patent 6,027,746 to Lech, et al., describes a liquid oral suspension incorporated into a softgel capsule wherein the decongestant is selected from a group which includes Ephedrine. The formulation also includes an active agent consisting of a particulate adsorbate. The drug delivery device is in chewable form. A composition including soybean oil, yellow beeswax and lecithin has been disclosed in U.S. Patent 6,309,677 to Gorenbein, et al. The patent discloses pharmaceutical composition containing extracts of carotinoids with soybean oil, yellow bees wax and lecithin in a form suitable for oral ingestion. U.S. Patent 5,175,002 is directed to a suspension formulation comprising soybean oil, lecithin and wax. However the active ingredient in this formulation is Amantidine hydrochloride. Statement of the Invention The present invention describes a process for preparing an orally administrable pharmaceutical formulation of Ephedrine Hydrochloride. The process comprises of preparing an oily matrix by heating suspending agent in suspension medium, cooling the matrix, incorporating surfactant into the matrix, adding expectorant in the matrix, mixing Ephedrine Hydrochloride into said matrix and encapsulating the oily matrix-embedded pharmaceutical complex into a capsule. Summary of the Invention It has been found that patient compliance is improved if a soft gelatin capsule is used for drug administration, because of its soft, elastic character which makes it easier to swallow when compared to conventional tablets or hard gelatin capsules. Furthermore, since the dosage form is generally swallowed without chewing, it is unnecessary to flavor or otherwise mask any unpleasant taste of the active pharmaceutical ingredients. Finally, unlike tablets, soft gelatin capsules do not chip or powder. Accordingly we sought to devise a soft gelatin capsule formulation of Ephedrine HC1 because of the reasons mentioned above. In accordance with preferred embodiment there is provided a process for producing an orally administrable pharmaceutical formulation consisting essentially of an active pharmaceutical ingredient embedded into an oily matrix; an expectorant; a surfactant; a suspending agent; and a suspension medium. In accordance with one preferred embodiment there is provided a process for producing an orally administrable pharmaceutical formulation into soft gelatin capsules, wherein the pharmaceutical formulation consists essentially of about 25 mg by weight of Ephedrine HC1, about 200 mg by weight of guaifenesin, about 0.1-5.0 mg by weight of yellow beeswax, about 10-15 mg by weight of lecithin and about 200-300 mg by weight of soybean oil. In accordance with one preferred embodiment there is provided a process for producing an orally administrable pharmaceutical formulation into soft gelatin capsules, wherein the pharmaceutical formulation consists essentially of about 12.5 mg by weight of Ephedrine HCI, about 200 mg by weight guaifenesin, about 0.1-5.0 mg by weight of yellow beeswax, about 10-15 mg by weight of lecithin and about 200-300 mg by weight of soybean oil. hi accordance with another preferred embodiment there are provided process for producing an orally administrable pharmaceutical formulation comprising the steps of preparing an oily wax matrix by heat-treating Soybean oil with yellow beeswax, until the beeswax is dissolved, cooling the matrix and incorporating lecithin into the matrix, adding guaifenesin in the matrix, blending the Ephedrine HCI with the resultant matrix and encapsulating the same into a soft gelatin capsule, wherein the formulation preferably comprises about 25 mg by weight of Ephedrine HCI as the active pharmaceutical ingredient, about 200 mg by weight of guaifenesin, about 0.1-5.0 mg by weight of yellow beeswax, about 10-15 mg by weight of lecithin and about 200-300 mg by weight of soybean oil. hi a preferred embodiment the capsule is a soft gelatin capsule drug delivery device. hi accordance with another preferred embodiment there is provided a method of making soft gelatin capsules of a pharmaceutical formulation consisting essentially of about 12.5 mg by weight of Ephedrine HCI, about 200 mg by weight of guaifenesin, about 0.1-5.0 mg by weight of yellow beeswax, about 10-15 mg by weight of lecithin and about 200-300 mg by weight of soybean oil. One possible advantage of preferred embodiments is that the Ephedrine (alone or together with one or more other components) is coated with wax by embedding the active in oily matrix, making the possible extraction of Ephedrine and its derivatives more difficult. Another possible advantage of preferred embodiments is that the drug delivery of the pharmaceutical formulation is achieved by a soft gelatin capsule and this makes it relatively difficult for someone to extract the active, unlike the case of a tablet as an OTC drug product. Hence the possibility of abuse of the drug is minimized. In yet another advantage, preferred formulations include guaifenesin in combination with Ephedrine HC1. This enables the composition to ease breathing for bronchial muscles and helps loosen phlegm and thin bronchial secretions to rid bronchial passageways of bothersome mucus and make coughs more productive. Another possible advantage of preferred embodiments is that preferred formulations include excipients like yellow beeswax and soybean oil, which are natural substances that make the extraction of ephedrine more difficult. This, in conjunction with the soft gelatin encapsulation makes it relatively a complex multi step process to extract amphetamines from the oily matrix. Thus the preferred embodiments considerably minimize the potential to abuse the drug product. Detailed Description of the Preferred Embodiment The present invention relates to. pharmaceutical formulations comprising Ephedrine HC1 for oral administration in the form of soft gelatin capsules. Preferred formulations also include guaifenesin, yellow beeswax, soybean oil and lecithin. In a preferred embodiment, the formulation consists essentially of the foregoing materials, hi preferred embodiments we have used soybean oil as a suspension medium and yellow beeswax as a suspending agent. Preferred formulations include guaifenesin that promotes lower respiratory tract drainage by thinning bronchial secretions, lubricates irritated respiratory track membranes through increased mucous flow and facilitates removal of viscous, inspissated mucus. As a result the sinus and bronchial drainage is improved and dry nonproductive coughs become more productive and less frequent. According to a preferred embodiment, wax forms part of the fill composition that is inside the gelatin shell. The wax and oil mixture makes it difficult to isolate the active from the formulation. The following examples illustrate preferred embodiments of pharmaceutical compositions comprising Ephedrine HC1 as principal ingredient. (Table Removed) Although ephedrine HC1 is a preferred form of the ephedrine, use of the free base or other salts of ephedrine is also contemplated. hi general, gelatin capsule formulations for soft gelatin capsule comprise raw gelatin, plasticizer, solvent and optional ingredients such as flavors and colorants. Typically the plasticizer includes glycerin or sorbitol. A preferred plasticizer in this case is glycerin. One preferred gelatin formulation for the soft gelatin capsule used in accordance with preferred embodiments includes gelatin in the range of about 40-45 % and a plasticizer in the range of about 18-25 %. Capsule formulation can also include other suitable additives, which impart specific characteristics such as the look and feel of the capsule. The following examples illustrate preferred embodiments of several soft-gelatin-shell Ephedrine HCl/Guaifenesin formulations. These examples illustrate particular embodiments of the invention and are not intended to limit the scope of the invention in any way. Example 3 (Table Removed) The various methods and techniques described above provide a number of ways to carry out the invention. Of course, it is to be understood that not necessarily all objectives or advantages described may be achieved in accordance with any particular embodiment described herein. Thus, for example, those skilled in the art will recognize that the formulations and methods may be formulated or performed in a manner that achieves or optimizes one advantage or group of advantages as taught herein without necessarily achieving other objectives or advantages as may be taught or suggested herein. Furthermore, the skilled artisan will recognize the interchangeability of various features from different embodiments. Similarly, the various features and steps discussed above, as well as other known equivalents for each such feature or step, can be mixed and matched by one of ordinary skill in this art to perform methods in accordance with principles described herein. Although the invention has ;been disclosed in the context of certain embodiments and examples, it will be understood by those skilled in the art that the invention extends beyond the specifically disclosed embodiments to other alternative embodiments and/or uses ,and obvious modifications and equivalents thereof. Accordingly, the invention is not intended to be limited by the specific disclosures of preferred embodiments herein, but instead by reference to claims attached hereto. We Claim: 1. A process for preparing an orally administrable pharmaceutical formulation of Ephedrine Hydrochloride comprising: preparing an oily matrix by heating 0.1-5 mg by weight of yellow beeswax in 200-300 mg by weight of soybean oil; cooling the matrix; incorporating 10-15 mg by weight of lecithin into the matrix; adding 200 mg by weight of guaifenesin in the matrix; mixing Ephedrine Hydrochloride into said matrix; and encapsulating the oily matrix-embedded pharmaceutical complex into a capsule to obtain orally administrable pharmaceutical formulation. 2. The process as claimed in claim 1, wherein the amount of Ephedrine Hydrochloride is 12.5 mg by weight. 3. The process as claimed in claim 1, wherein the amount of Ephedrine Hydrochloride is 25 mg by weight. 4. The process as claimed in claim 1, wherein the capsule is a soft gelatin capsule. 5. A process for preparing an orally administrable pharmaceutical formulation as substantially herein described with reference to the examples.

Documents:

128-del-2002-abstract.pdf

128-del-2002-claims.pdf

128-del-2002-complete specification (granted).pdf

128-del-2002-correspondence-others.pdf

128-del-2002-correspondence-po.pdf

128-del-2002-description (complete).pdf

128-del-2002-form-1.pdf

128-del-2002-form-13.pdf

128-del-2002-form-19.pdf

128-del-2002-form-2.pdf

128-del-2002-form-26.pdf

128-del-2002-form-3.pdf

128-del-2002-form-5.pdf

128-del-2002-gpa.pdf

128-del-2002-petition-138.pdf