IL131317A

IL131317A - Binder for pharmaceutical compositions

Info

Publication number: IL131317A
Application number: IL131317A
Authority: IL
Original assignee: Cts Chemical Ind Ltd
Priority date: 1999-08-09
Filing date: 1999-08-09
Publication date: 2006-08-01
Also published as: EP1200069A1; CA2378987C; AU5842800A; IL131317A0; CA2378987A1; WO2001010415A1; WO2001010415B1

Description

A binder for pharmaceutical compositions CTS Chemical Industries Ltd.

C. 117838 A BINDER FOR PHARMACEUTICAL COMPOSITIONS FIELD OF THE INVENTION The present invention is generally in the field of pharmaceutics and concerns a pharmaceutical composition comprising an active ingredient and a binder holding together the constituents of the composition.

BACKGROUND OF THE INVENTION AND PRIOR ART Pharmaceutical compositions typically consist of at least one active ingredient and several excipients. The excipients may be disintegrants, which assist in releasing the active ingredient under the desired conditions, lubricants, which improve ejection from machine tooling, glidents, which improve flow, binders, which bind together different ingredients of the composition, etc.

Binders are of special importance in solid dosage forms, like tablets, pellets, microgranules, and sachets, where they are essential for holding together several different solid ingredients.

Pharmaceutically acceptable binders that are in wide use include, for example: starch, starch derivatives, polyvinilpyrolidone (PVP), alginate derivatives, and glucose.

Echinacea is well known as a food additive, and as such is known to be safe for consumption. It was also proposed as a pharmaceutically active ingredient, and the British Herbal Pharmacopeia (1996) defines it as an immunostimulant.

Derwent Abstract No. 012237708 describes a drug that comprises paracetamol, caffeine, Echinacea and several other ingredients for use as an analgesic. Derwent Abstract No. 012234518 describes a cold treatment agent that comprises Echinacea and antipyretic and anti-inflammatory agent. 01 178383V33-01 Austrian Patent No. 385654 describes a preparation comprising as a carrier granulated mass, coated with silicic acid and oil. The granulated mass ma)' be prepared from a variety of substances, including, inter alia, Echinacea extract.

European Patent Application No. 0 743 062 describes a method for the manufacture of an effervescent preparation from fresh plants, such as Echinacea, including heating plant juice, mixing the same with saccharides and subsequently drying and pulverizing so as to obtain a powder to be processed into tablets or granulates. 01178383\33-01 GENERAL DESCRIPTION OF THE INVENTION In accordance with the invention powder or extract of Echinacea is used as a binder in solid pharmaceutiacal compositions, e.g. compositions in the form of tablets, pellets, capsules, microgranules, powders, etc.

Echinacea powder or extract (hereiafter Echinacea preparation) may be obtained from Echinacea leafes, roots, or whole plants. Examples of Echinacea species that preparations thereof are suitable to serve as binders according to the present invention are those known as Echinacea purpurea, Echinacea angustifolia, Echinacea pallida, Echinacea paradoxa, Echinacea tennesseensis, Echinacea sanguinea, Echinacea simulata and Echinacea atrotubens.

Examples of Echinacea preparations are Echinacea angustifoliae herba et rad , Echinacea pallidae herba, Echinacea pallidae radix, Echinacea purpureae herba, and Echinacea purpureae redix.

Thus, the present invention provides, by a first of its aspects, a pharmaceutical composition comprising particulate matter containing at least one pharmaceutically active ingredient and a binder, characterized in that said binder comprises a binding-effective amount of Echinacea preparation.

The term "binding-effective amount" should be understood to denote an amount of Echinacea preparation effective in binding or assisting in binding together components of the composition. The binder may consist of Echinacea preparation or may be a mixture of Echinacea preparation and other ingredients, with the Echinacea preparation having a role in binding the compositions' component together. The property being included in a binding-effective amount is manifested in that when the Echinacea preparation is removed, the composition's other components will not bind to one another or will bind only minimally. In the presence of binding-effective amount of Echinacea preparation, there may be a measurable improvement of physical properties such as hardness (in tablets) and of flowability (in powders) in comparison to the same tablets or powders in the absence of binding-effective amount of Echinacea preparation. Typically, the Echinacea preparation will constitute at least about 20% of the binding component - 3 - of the composition, preferably at least about 40%, and particularly preferably at least about 60% and desirably above 80% of the binding component of the composition.

The pharmaceutical composition is typically formed into a dosage form such as a tablet or a capsule. At times, the formed pharmaceutical composition, e.g. in the form of small pellets, powder, and the like, may be incorporated into a capsule or a sachet.

The active ingredient may be an analgesic, an antipyretic agent, an anti-inflammatory agent, a vitamin, an expectorant, an antibiotic, etc. These types of active ingredients are but an example and the invention is not limited thereto. On the contrary, the pharmaceutical compositions of the invention may be used for essentially all types of different active ingredients, which are compatible with the Echinacea preparation. Furthermore, the pharmaceutical composition of the invention is intended for oral administration and thus the active ingredient should be adapted for such form of administration, namely, should be orally bioavailable.

Specific examples of active ingredients are paracetamol, carbocysteine, dextromethorphan, loratadine and vitamin C.

The invention also provides, by another of its aspects, a process for forming a pharmaceutical composition, comprising: (a) preparing a mixture comprising at least one active ingredient and an excipient; (b) adding a binder to said mixture; and (c) processing said mixture to yield an administration form, in which form said binder binds together ingredients of the composition; said process being characterized in that said binder comprises a binding-effective amount of Echinacea preparation and said processing comprises applying conditions in which said preparation binds together ingredients of the composition.

By a still further aspect, the present invention provides a method of administering Echinacea preparation and a pharmaceutically active ingredient to an individual, comprising: (a) preparing a mixture comprising said active ingredient, an excipient and the Echinacea preparation; (b) processing the mixture to obtain an administration form, said processing being under conditions such that said preparation bind together all the ingredients in the administration form; (c) administering said administration form to the individual.

The invention even further provides use of an excipient of Echinacea preparation and, an active ingredient to yield a pharmaceutical composition wherein said preparation binds together components of the composition.

The invention will now be illustrated in the following non-limiting examples.

BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 shows the size distribution of the particles obtained in example 1.

Fig. 2 shows the size distribution of the particles obtained in example 2.

EXAMPLES In the following example 1 the Echinacea preparation was Echinacea purpurea E, supplied by Pharmabeta AG, Switzerland and in examples 2, 3, and 4 the Echinacea preparption was Echinacea Plante Extrait Sec supplied by Martin Bower, France.

Example 1: Preparation of Paracetamol tablets with Echinacea as a single binder. 11.6 g of Echinacea were dissolved in 60 ml of purified water and the solution was poured drop-wise on 215 g of paracetamol and mixed with it manually. The mixture was dried in 45°C (LOD=1.0%). The resulting dry granulate was ground in a 1 mm net. 1 g magnesium stearate and 9.0 g of Primojel were added. The mixture was moistured with a little water and dried (LOD=2.8%). The dried mixture was then pressed to give round tablets of 13 mm diameter, each - 5 - containing 500 mg of paracetamol. The hardness of the tablets was 44±5 N. The size distribution of the resulting particles is shown in Figure 1.

Example 2: Preparation of carbocystein capsules with Echinacea as a single binder. g of Echinacea preparation were dissolved in 30 ml water. 187.5 g of carbocystein were mixed with 4 g of Avicel.

The Echinacea solution was added to the mixture of the powders and manually stirred to granulation. The granulate was dried at 40°C (LOD=0.7%). The dry granulate was ground on a 1 mm net and mixed with 7 g Avicel and 1 g magnesium stearate to give the final blend. The final blend was filled inside hard gelatin capsules of capsule size no. 0, 375 mg active ingredient per capsule. The particle size distribution of the final blend is shown in Figure 2.

Example 3: Application of dextromethorphan on pellets, using Echinacea as a binder. 8 g of Echinacea were dissolved in 300 ml of purified water, and 4 g of PEG 4000 were added to the solution. 40 g of dextromethorphan Fffir were added to the solution to give a dispersion. The dispersion was applied to Neutral pellets No. 20 during heating. 40 g of dextromethyorphan HBr were suspended in tge a/m solution and sprayed on neutral sugar sphere (pellets size 20) using Glatt-Wurster equipment. Coated pelletswere filled inside hard gelatin capsules.

Example 4: Preparation of Loratadine tablets by direct compression with Echinacea. g of Loratadine were mixed with 25 g of Echinacea. The mixture was sieved on a 50 mesh sieve. 163 g of Lactose DC were added and mixed. 2 g of magnesium stearate were added and mixed to give the final mixture. The final mixture was pressed in a die to give tablets that contained 100 mg and 200 mg active ingredient. The 100 mg tablets had hardness of 99±1 N and the 200 mg tablets had hardness of 85±1 N.

Claims

131317/2 -7- CLAIMS:

1. A pharmaceutical composition consisting of at least one pharmaceutically active ingredient and at least one excipient, wherein said at least one excipient includes a binder, said binder comprising a binding effective amount of Echinacea extract, and being mixed with other ingredients of the composition.

2. A pharmaceutical composition according to claim 1, wherein each said pharmaceutically active ingredient is selected from the group consisting of analgesic, antipyretic, anti-inflammatory, anti-histaminic, expectorating, and antibiotic agents.

3. A pharmaceutical composition according to Claim 1 or 2, wherein said binder holds said elements to yield a dosage form of the active ingredient.

4. A pharmaceutical composition according to Claim 3, wherein said dosage form is in the form of a tablet.

5. A pharmaceutical composition according to Claim 3, comprising pellets; each of which comprising said active ingredient and said binder.

6. A capsule containing a pharmaceutical composition according to any of Claims 1, 2, 3 or 5.

7. A pharmaceutical composition according to any one of claims 1 -6, wherein the active ingredient is paracetamol, carbocysteine, dextromethorphan or loratadine.

8. A pharmaceutical composition according to any one of claims 1-7, comprising only one active ingredient.

9. A pharmaceutical composition according to any one of claims 1 -8, wherein the weight of said Echinacea extract constitutes between about 2% and about 12% of the weight of said pharmaceutically active mixture. 8 3 1 7/3

10. A process for forming a pharmaceutical composition consisting at least one active ingredient and at least one excipient, wherein said excipient includes a binder; the process comprising a step of mixing said at least one pharmaceutically active ingredient with said binder, wherein said binder comprises a binding-effective amount of Echinacea extract.

11. A process according to claim 10, wherein each said pharmaceutically active ingredient is selected from the group consisting of analgesic, antipyretic, antiinflammatory, anti-histaminic, expectorating, and antibiotic agents.

12. The process of claim 10, wherein said active ingredient is selected from the group consisting of paracetamol, carbocysteine, dextromethorphan, and loratadine.

13. A process according to any one of claims 10 to 12, comprising only one active ingredient.

14. A process according to any one of claims 10 to 13, wherein the weight of said Echinacea extract constitutes between about 2% and about 12% of the weight of said pharmaceutically active mixture.

15. In a method for producing a pharmaceutical composition as claimed in claim 1, in tablet form, an improved method for obtaining harder tablets, the improvement comprising: adding to said composition a binding effective amount of Echinacea extract.

16. In a method for producing a pharmaceutical composition as claimed in claim 1 , in powder form, an improved method for obtaining powder with improved flowability, the improvement comprising: adding to said composition a binding effective amount of Echinacea extract. For the Applicants REINHOLD COHN & PARTNERS 01 178383\33-O l