|Title of Invention||
"process for preparing orally administrable pharmaceutical formulation comprising pseudoephedrine 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 Pseudoephedrine HCl as one of the active ingredients. 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 30.5 mg by weight of Pseudoephedrine HCl, 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 PSEUDOEPHEDRINE HYDROCHLORIDE
Background of the Invention Field of the Invention
This invention in general relates to process for preparing an orally administrable pharmaceutical formulation and in particular to a process for producing a pharmaceutical formulation prepared into a soft gelatin capsule containing Pseudoephedrine hydrochloride as one of its active ingredients.
Description of the Related Art
Pseudoephedrine hydrochloride is a drug that has serious potential for abuse. 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.
Pseudoephedrine HC1 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.
Pseudoephedrine HC1 tablets used for the temporary relief of nasal congestion caused by common cold are commercially available in various strengths. However, soft gelatin formulations containing only Pseudoephedrine HC1 and Guaifenesin as actives are not commercially available. The following table contains details of commercially available soft gelatin formulations comprising Pseudoephedrine HC1 and Guaifenesin or Pseudoephedrine in combination of antihistamines or analgesics.
Pharmaceutical formulations comprising Pseudoephedrine HCl and Guaifenesin as principal ingredients are known. U. S. Patent 5,141,961 to Coapman et al. describes a soft gelatin capsule comprising as a second pharmaceutical active, Pseudoephedrine HCl and Guaifenesin. This disclosure is directed to a highly concentrated liquid pharmaceutical composition solubilized using polyethylene glycol. The process therein described discloses the use of solubilizing agents like polyvinylpyrrolidone or glycol for solubilizing the active ingredients.
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 therein comprises an effective amount of xanthan gum and microcrystalline cellulose.
A composition including soybean oil, yellow beeswax and lecithin has been disclosed in the U.S. Patent 6,309,677 to Gorenbein et. al. The patent discloses pharmaceutical composition containing extracts of carotenoid with soybean oil, yellow 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 in this formulation is Amantidine hydrochloride.
Statement of the Invention The present invention provides a process for preparing an orally administrable pharmaceutical formulation of Pseudoephedrine hydrochloride, which comprises of preparing an oily matrix by heating a suspending agent in a suspension medium, cooling the matrix; incorporating a surfactant into the matrix; adding an expectorant in the matrix; mixing pseudoephedrine 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 Pseudoephedrine HCl because of the reasons mentioned above.
In accordance with one preferred embodiment there is provided 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 are provided soft gelatin capsules of a pharmaceutical formulations consisting essentially of about 30.5 mg by weight of Pseudoephedrine HCl, about 200 mg by weight of guaifenesin, about 0.1-0.5 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 another preferred embodiment there are provided methods of making a pharmaceutical formulation comprising the steps of preparing an oily matrix by heating yellow bees wax in soybean oil, until the yellow bees wax melts and mixes with soybean oil, cooling the matrix, incorporating lecithin into the matrix, adding guaifenesin in the matrix, mixing an active pharmaceutical ingredient into said matrix; and encapsulating the oily matrix-embedded pharmaceutical complex into a capsule, wherein Pseudoephedrine HC1 is the active pharmaceutical ingredient. Preferably the amounts of each ingredient are as follows: about 30.5 mg by weight of Pseudoephedrine HC1, 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. In a preferred embodiment, the capsule is a soft gelatin capsule drug delivery device.
One possible advantage of preferred embodiments that the pseudoephedrine (either alone or along with one or more excipients) is coated with wax by embedding the active into wax matrix, making the possible extraction of Pseudoephedrine and its derivatives further difficult. Yet another 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 another possible advantage, preferred formulations have guaifenesin in combination with Pseudoephedrine HC1. Guaifenesin promotes lower respiratory tract drainage by thinning bronchial secretions, lubricates irritated respiratory tract membranes through increased mucous flow, and facilitates removal of viscous, inspissated mucus. As a result of pseudoephedrine and guaifenesin combination, sinus and bronchial drainage is improved, and dry, nonproductive coughs become more productive and less frequent.
Another possible advantage of preferred embodiments that preferred formulations include excipients like yellow beeswax and soybean oil, which are natural substances that make the extraction of Psuedoephedrine more difficult. This, in conjunction with the soft gelatin encapsulation, makes it a relatively complex multi-step process to extract amphetamines from the oily matrix. Thus preferred embodiments considerably minimize the potential to abuse the drug product.
Detailed Description of the Preferred Embodiment
The present invention relates to pharmaceutical formulations having Pseudoephedrine, preferably Pseudoephedrine HC1, as an active ingredient for oral administration in the form of soft gelatin capsules. Preferred formulations also comprise guaifenesin, yellow beeswax, soybean oil and lecithin. In a preferred embodiment, the formulation consists essentially of the foregoing materials. We have used soybean oil in the preferred embodiment as a suspension medium and yellow beeswax as a suspending agent.
Preferred formulation includes 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 non-productive coughs become more productive and less frequent.
According to preferred embodiments, 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 Pseudoephedrine HC1 as principal ingredient.
Ingredients Composition by weight
Pseudoephedrine HC1, USP 30.5 mg
Guaifenesin, USP 200 mg
Yellow Beeswax 0.1-5.0 mg
Lecithin, NF 10-15mg
Soybean Oil, USP 200-300 mg
Although pseudoephedrine HCl is a preferred form of the pseudoephedrine, use of the free base or other salts of pseudoephedrine is also contemplated.
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. A 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 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 Pseudoephedrine 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.
Ingredient Percentage by weight
Ingredient Percentage by weight
Gelatin 58. 5%
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.
1. A process for preparing an orally administrable pharmaceutical formulation of Pseudoephedrine hydrochloride comprising:
preparing an oily matrix by heating 0.1-5.0 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 30.5 mg by weight of pseudoephedrine hydrochloride into said matrix; and
encapsulating the oily matrix-embedded pharmaceutical complex into a capsule to obtain orally administrable pharmaceutical formulation.
The process as claimed in claim 1, wherein the capsule is a soft gelatin
3. A process for producing an orally administrable pharmaceutical formulation as substantially herein described with reference to the examples.
|Indian Patent Application Number||127/DEL/2002|
|PG Journal Number||29/2008|
|Date of Filing||20-Feb-2002|
|Name of Patentee||Strides Inc|
|Applicant Address||37 Veronica Avenue, Somerset, NJ 08873.U.S.A.|
|PCT International Classification Number||A61J 3/07|
|PCT International Application Number||N/A|
|PCT International Filing date|