Title of Invention

"PROCESS FOR PREPARING AN ORALLY ADMINISTRABLE PHARMACEUTICAL FORMULATION"

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 Pseudoephedrine HCI as the active ingredient. The active pharmaceutical ingredient is embedded into an oily matrix, also the formulation comprises of viscosity imparting agents, a surfactant; a suspending agent; and a suspension medium. The viscosity-imparting agents are partially hydrogenated vegetable oil and colloidal silicon dioxide, the surfactant is lecithin, the suspending agent is yellow beeswax, and the suspension medium is soybean oil. The formulation comprises of about 60 mg by weight of Pseudoephedrine HCI, about15-25 mg by weight of partially hydrogenated vegetable oil, about 10-20 mg by weight of yellow beeswax, about 2-8 mg by weight of lecithin, about 2-8 mg by weight of silicon dioxide; and about 150-250 mg by weight of soybean oil. Also the invention is addressed at the process for preparing the formulation.

Full Text

ORALLY ADMINISTRABLE PHARMACEUTICAL FORMULATION Background of the Invention Field of the Invention [001] This invention in general relates to orally administrable pharmaceutical formulations and in particular to a pharmaceutical formulation prepared into a soft gelatin capsule containing Pseudoephedrine Hydrochloride as the active ingredient. Description of the Related Art [002] Pseudoephedrine Hydrochloride is a drug that has got serious abuse potential. This is so because Pseudoephedrine or Ephedrine could be extracted from various drug products containing Pseudoephedrine Hydrochloride and can be converted into amphetamines. Amphetamines have potentially lethal stimulant effects on the central nervous system and heart and it is thereof important if such abuse potential could be minimized. [003] The patient compliance is improved if soft gelatin capsule is used for drug administration, because of its soft, elastic character making it easier to swallow when compared to conventional tablets or hard gelatin capsules. [004] Further more, since the dosage form is generally swallowed, 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. [005] Pseudoephedrine HCI is a vasoconstrictor, which produces vasoconstriction by stimulating (alpha)-receptors within the mucous of the respiratory tract. Clinically Pseudoephedrine shrinks the swollen mucous membranes, reduces tissue hyperemia, edema and nasal congestion, and increases nasal airway patency. Its use is therefore significant in the relief from nasal congestion. [006] Pseudoephedrine HCI tablets used for the temporary relief of nasal congestion caused by common cold are commercially available in various strengths. However, soft gelatin formulations comprising Pseudoephedrine HCI are not commercially available. The following table contains details of commercially available soft gelatin formulations comprising Pseudoephedrine HCI or Pseudoephedrine in combination of antihistamines or analgesics. Active Ingredient/s Brand Name / Manufacturer (Each Capsule contains) Pseudoephedrine H Cl Nyquil / 30mg Proctor & Gamble Doxylamine succinate 6.25mg Dextromethorphan H Br 10mg Acetaminophen 200mg Pseudoephedrine H Cl Dayquil / 30mg Proctor & Gamble Dextromethorphan H Br 10mg Acetaminophen 200mg Pseudoephedrine HCI Alka-Seltzer Plus 30mg Night-Time Cold Medicine Doxylamine succinate Bayer 6.25mg Dextromethorphan H Br 10mg Acetaminophen 325mg Pseudoephedrine H Cl Alka-Seltzer Plus 30mg Cold & Cough Medicine Chlorpheniramine Maleate Bayer 2mg Dextromethorphan H Br 10mg Acetaminophen 325mg Pseudoephedrine H Cl Alka-Seltzer Plus 30mg Cold & Cough Medicine Chlorpheniramine Maleate Bayer 2mg Acetaminophen 325mg Pseudoephedrine H Cl Alka-Seltzer Plus 30mg Chlorpheniramine Cold & Cough Medicine Maleate 2mg Bayer Acetaminophen 325mg Pseudoephedrine H Cl Alka-Seltzer Plus 30mg Acetaminophen Cold & Sinus Medicine 325mg Bayer Pseudoephedrine H Cl Alka-Seltzer Plus 30mg Dextromethorphan Cold & Cough Medicine HBMOmg Bayer Acetaminophen 325mg [007] U. S. Patent 5,409,907 to Blase et. al describes a pharmaceutical suspension comprising a therapeutic amount of pharmaceutical active selected from the group consisting of acetaminophen, famotidine, pseudoephedrine hydrochloride, Chlorpheniramine maleate, astemizole, dextromethorphan hydrobromide, guaifenesin, diphenhydramine hydrochloride, loperamide hydrochloride, simethicone, antacids, and combinations thereof. However, the suspending system described herein comprises of an effective amount of xanthan gum and microcrystalline cellulose. The current invention has employed a different suspension medium and a suspending agent. [008] A composition including soybean oil, yellow beeswax and lecithin has been disclosed in the U.S Patent 6,309,667 to Horvath et. al. This disclosure is not addressed at Pseudoephedrine HCI as an ingredient in combination with the other excipients. [009] U.S. Patent 5,175,002 is addressed at a suspension formulation comprising soybean oil, lecithin and wax. However the active in this formulation is Amantidine Hydrochloride. [0010] U.S. Patent 5,112,602 to Beurline et al. discloses an oral pharmaceutical liquid suspension comprised of theophyline as the active agent, silicon dioxide, a wetting agent and a hydrocolloid gum. Summary of the Invention [0011] Accordingly we sought to device a soft gelatin capsule formulation of Pseudoephedrine HCI because of a variety of reasons. Primarily it is relatively difficult to extract Pseudoephedrine or Ephedrine from a soft gel drug delivery device. Another reason is that a soft gelatin capsulated formulation provides better patient compliance. [0012] In accordance with one preferred embodiment there are provided soft gelatin capsules of a pharmaceutical formulations comprising 60 mg by weight of Pseudoephedrine HCI, 10-20 mg by weight of yellow bees wax, 15-25 mg by weight of partially hydrogenated oil, 2-8 mg by weight of lecithin, 2-8 mg by weight of silicon dioxide and 150-250 mg by weight of soybean oil. [0013] In accordance with another preferred embodiment there are provided methods of making a pharmaceutical formulation comprising the steps of preparing an oily matrix consisting of soybean oil and partially hydrogenated vegetable oil, the oily blend is heat treated with beeswax, to have the beeswax dissolved into the matrix, the steps further comprises blending lecithin to said oily matrix and mixing the active pharmaceutical ingredient into the said matrix. Colloidal silicon dioxide is added to the complex to form a homogeneous blend and the resultant pharmaceutical complex is enclosed into to a capsule, wherein used is 60 mg by weight of Pseudoephedrine HCI, 10-20 mg by weight of yellow bees wax, 15-25 mg by weight of partially hydrogenated oil, 2-8 mg by weight of lecithin, 2-8 mg by weight of silicon dioxide and 150-250 mg by weight of soybean oil. Also is the preferred embodiment to dispose the said pharmaceutical complex into a soft gelatin drug delivery device. [0014] It is a principal advantage of the preferred embodiment that the active ingredient in this formulation is coated with wax, making the possible extraction of Pseudoephedrine and its derivatives further difficult. Yet another advantage of the preferred embodiment 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. [0015] It is also an advantage of the preferred embodiment that the formulation comprises of excipients like yellow beeswax and soybean oil, which are natural substances that make the extraction further difficult. This, in conjunction with the soft gelatin encapsulation makes it relatively a complex multi step process to extract pseudoephedrine from the oily matrix. Thus this preferred embodiment considerably minimizes the potential to abuse the drug product. Detailed Description of the Preferred Embodiment [0016] The present invention relates to pharmaceutical formulations comprising Pseudoephedrine HCI for oral administration in the form of soft gelatin capsules. The formulation also comprises of partially hydrogenated vegetable oil, yellow bees wax, colloidal silicon dioxide, soybean oil and lecithin. We have used soybean oil in the preferred embodiment as a suspension medium and yellow bees wax as a suspending agent. Hydrogenated vegetable oil has been used as a viscosity inducing agent and colloidal silicon dioxide is used to achieve uniform dose dispersion. [0017] According to the preferred embodiment, wax forms part of the fill composition that is inside the gelatin shell. A coating of the product in wax and oil mixture is achieved making it difficult to isolate the active from the formulation. [0018] The following examples illustrate preferred embodiments of pharmaceutical compositions comprising Pseudoephedrine HCI as principal ingredient. EXAMPLES Example 1 Ingredients Composition by weight Pseudoephedrine HCI, DSP 60 mg Yellow Beeswax 10-20 mg Partially Hydrogenated Vegetable Oil 15-25 mg Lecithin, NF 2-8 mg Colloidal Silicon Dioxide 2-8 mg Soybean Oil, USP 150-250 mg [0019] In 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. The preferred plasticizer in this case is glycerin. One preferred gelatin formulation for the soft gelatin capsule used in accordance with preferred embodiment includes gelatin in the range of 40-45 % and a plasticizer in the range of 18-25 %. Capsule formulation can also include other suitable additives, which impart specific characteristics such as the look and feel of the capsule. [0020] The following examples illustrate preferred embodiments of several soft-gelatin-shell Pseudoephedrine HCI formulations. These examples illustrate particular embodiments of the invention and are not intended to limit the scope of the invention in any way. Example 2 Ingredient Percentage by weight Gelatin 43.4% Glycerin 20.0% Water 36.6% Example 3 Ingredient Percentage by weight Gelatin 58.5% Glycerin 31.5% Water 10.0% [0021] Certain modifications and improvements of the disclosed invention will occur to those skilled in the art without departing from the scope of invention, which is limited only by the appended claims. What is claimed is: 1. An orally administrable pharmaceutical formulation comprising an active pharmaceutical ingredient embedded into an oily matrix, viscosity imparting agents, surfactant; suspending agent; and suspension medium. 2. The orally administrable pharmaceutical formulation according to claim1, wherein the said active pharmaceutical ingredient is Pseudoephedrine Hydrochloride. 3. The orally administrable pharmaceutical formulation according to claim1, wherein the said viscosity-imparting agents are partially hydrogenated vegetable oil and colloidal silicon dioxide. 4. The orally administrable pharmaceutical formulation according to claiml, wherein the said surfactant is lecithin. 5. The orally administrable pharmaceutical formulation according to claim1, wherein the said suspending agent is yellow beeswax. 6. The orally administrable pharmaceutical formulation according to claim1 , wherein the said suspension medium is soybean oil. 7. An orally administrable pharmaceutical formulation comprising as its ingredients: about 60 mg by weight of Pseudoephedrine HCI, about 1 0-20 mg by weight of yellow beeswax, about 15-25 mg by weight of partially hydrogenated vegetable oil, about 2-8 mg by weight of lecithin, about 2-8 mg by weight of colloidal silicon dioxide; and about 150-250 mg by weight of soybean oil. 8. The orally administrable pharmaceutical formulation according to claim 7, wherein the surfactant is employed to provide lubricity to the matrix. 9. The orally administrable pharmaceutical formulation according to claim? or 8, wherein the said oily matrix-embedded active pharmaceutical complex is disposed into a capsule. 10. The orally administrable pharmaceutical formulation according to claim9, wherein the said capsule is a soft gelatin capsule. 11. The orally administrable pharmaceutical formulation according to claim7, wherein the said partially hydrogenated vegetable oil and colloidal silicon dioxide are employed as agents to enhance viscosity. 12. A process for preparing an orally administrable pharmaceutical formulation comprising preparing an oily matrix consisting of soybean oil and partially hydrogenated vegetable oil, heat treating the oily blend with beeswax enabling the beeswax to dissolve into the oily matrix, blending lecithin to the oily matrix, mixing the active pharmaceutical ingredient with the matrix, adding to the matrix colloidal silicon dioxide to form a homogeneous blend thereof and disposing the resultant pharmaceutical complex into a capsule. 13. The process for preparing an orally administrable pharmaceutical formulation according to claim 12, wherein the said active pharmaceutical ingredient is Pseudoephedrine Hydrochloride. 14. The process for preparing of an orally administrable pharmaceutical formulation according to claim 12, wherein the said capsule is a soft gelatin capsule.

Documents:

129-del-2002-abstract.pdf

129-del-2002-claims.pdf

129-del-2002-correspondence-others.pdf

129-del-2002-correspondence-po.pdf

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

129-del-2002-form-1.pdf

129-del-2002-form-13.pdf

129-del-2002-form-19.pdf

129-del-2002-form-2.pdf

129-del-2002-form-3.pdf

129-del-2002-form-5.pdf

129-del-2002-gpa.pdf

129-del-2002-petition-138.pdf