FR2792200A1 - Tobacco substitute tablets or pastilles contain nicotine salt and base to raise pH of user's mouth and liberate nicotine - Google Patents

Abstract

Tablets or pastilles for sucking, containing a salt of nicotine and a solid powdered base in sufficient quantity to raise the pH of the user's mouth to at least 8.5, thus liberating nicotine base. The preparations are formed by mixing the ingredients in dry powdered form containing at least 805 excipients, and compressing the dry powder. The base used is preferably an alkali metal carbonate, in sufficient quantity to raise the liquid in the user's mouth to pH 8.5 - 9.5. The nicotine salt used is preferably the hydrogen tartrate, hydrochloride or sulfate, present in a quantity to give a unit dosage of nicotine base of 0.3-0.6 mg. The compositions preferably also contain a granulating agent which is premixed with nicotine granules, the mixture combined with the base, then mixed with one or more other ingredients including flavors and colors.

Description

The present invention relates to preparations of a tobacco substitute and

  a process for their preparation. Smoking is currently recognized as a significant health risk, although the alkaloid in tobacco is not itself harmful. Many smokers have great difficulty in

  quit smoking, even when recommended by medical advice.

  Trials have been conducted to produce tobacco substitute preparations which contain nicotine and which allow the user to enjoy the pleasant effects of nicotine absorption without the risk of smoking. One of the problems in producing preparations containing nicotine is the control of the release of nicotine. Nicotine is absorbed by mouth only when it is in the form of the free base. The pH of saliva is generally acidic, but varies widely depending on the food and drink recently consumed. Also, preparations containing nicotine

  tend to lose their power of accumulation.

  According to a first aspect of the present invention, there is provided a tobacco substitute preparation in the form of a tablet or lozenge which contains nicotine in the form of a pharmaceutically acceptable salt, as well as a solid base. powder which is present in an amount sufficient to raise the pH in the mouth of the user to at least 8.5, thereby releasing the free base nicotine, said preparation having been formed by compression of a mixture of powdered ingredients dry and containing at least 80% by weight of formation excipients

dry powder tablets.

  Provided that the solid powder base is present in an amount such that a pH of about 8.9 or more is reached, for example a pH in the range of 8.5 or 8.9 to about 10, this ensures that approximately 90% of the available nicotine is converted to the free base form and can therefore be absorbed orally. The preparation can be formulated with buffering agents so that the pH developed in the mouth of the user is buffered to a suitable level, for example about 8.5 to 10, preferably about 8.5 to 9.5. The solid powder base is advantageously used in an amount sufficient to maintain a pH in the mouth of the user of at least 8.9 for at least 5

  minutes after taking the tablet.

  Nicotine is in the form of a pharmaceutically acceptable salt such as nicotine acid tartrate, since the free base nicotine is volatile and would escape from a tablet or lozenge preparation. However, when the tablet or lozenge according to the present invention is placed in the mouth and begins to dissolve, the pH rises to at least about 8.9 due to the presence of the strong base and this converts the salt of free base nicotine, so it's

  easily absorbed into the oral cavity.

  As an alternative to the acid tartrate, it is possible to use other pharmaceutically acceptable salts such as the hydrochloride or the sulfate. The solid powder base is preferably an alkali metal carbonate, for example carbonate

sodium or potassium.

  In order to avoid a premature loss of potency or an uneven release of nicotine in the mouth of the user, it is important to carefully control the manufacture of the preparation put into tablet. Water should be avoided at all stages of manufacture and tablets or lozenges are produced by compressing dry powder ingredients containing at least 80% by weight of tablet excipients and, most preferably, between about 85 and

% in weight.

  Excipients suitable for tabletting include sugars, for example directly compressible sucrose, lactose and glucose

and cellulose derivatives.

  By varying the amounts or proportions of sugar / xanthan gum / lactose in the formula, various times of disintegration of the tablet and

  base release times, between 3 and 10 minutes, can be obtained.

  In the manufacture of the preparations according to the present invention, the first step is a granulation of the nicotine salt. This is done by mixing the nicotine salt with a granulating agent such as a vegetable gum. A colorant may be included at this stage to assist the operator in ensuring the consistency of salt incorporation in the remaining ingredients. The granulated mixture is then mixed with the solid powder base and the tablet excipients are mixed until a free flowing, powdered, dry, uniform mixture is obtained. The tablets are then formed by compressing the mixture into

a tablet press.

  The tablet or lozenge can be flavored if necessary, for example using mint, anise, chocolate, orange-chocolate mixture or licorice. In addition, the tablet or lozenge can be colored with coloring agents.

  pharmaceutically acceptable food coloring.

  Nicotine salt is normally present in the tablet or lozenge in an amount between about 0.86 and 1.72 mg, thereby providing

  a unit dose of nicotine base between 0.3 and 0.6 mg.

  The following example will illustrate formulations according to the present invention. The raw materials indicated in the following formulation were mixed and compressed into tablets using a conventional tablet machine.

Example

  Raw materials mg per tablet Nicotine hydrogen tartrate 1.08 Icing sugar 37.00 Ludipress (modified lactose) 78.92 Keltrol F (xanthan gum) 4.80 Silicon dioxide - Aerosil 200 0.48 Miciotal DCE (delivery excipient Cellulose-derived tablet) 96.00 Mint flavor F 8554 6, 72 Anhydrous sodium carbonate (base) 10.00 Aspartame (sweetener) 0.20 Magnesium stearate (tablet lubricant) 1.20 Stearic acid ( tablet lubricant) 2.40 Green dye 79821 1.20

240.00

  The procedure was as follows. First, the nicotine salt was granulated by mixing in a rotary drum with Keltrol F, the green dye and aspartame, was passed through a 250 ktm sieve and collected in another dry and clean drum. . The solid powder base, silicon dioxide and flavorings were then added to the new drum, which was sealed and shaken on rollers. After about 10 minutes, icing sugar and other tablet excipients were added and mixed continuously for about 15 minutes. Finally, the buffering agents were added and mixed continuously for another 10 to 15 minutes. Tablets were manufactured by compression in a tablet machine and were packaged in plastic containers.

  sealed polyethylene which may have an internal vapor resistant coating.

Claims (7)

  1. Preparation of tobacco substitute in the form of a tablet or lozenge, characterized in that it comprises nicotine in the form of a pharmaceutically acceptable salt, associated with a solid powder base which is present in an amount sufficient to raise the pH in the user's mouth to at least 8.5, thereby releasing the free base nicotine, said preparation having been formed by compression of a mixture of ingredients in dry powder and containing at least 80% by weight of excipients for tableting in the form of dry powder. 2. Preparation according to claim 1, characterized in that the base   solid powder is an alkali metal carbonate.   3. Preparation according to claim 1 or 2, characterized in that the solid powder base is present in an amount sufficient to raise the pH of the composition in the mouth of the user to a pH value between about 8.5 and 9.5.   4. Preparation according to any one of the preceding claims,   characterized in that the nicotine salt is hydrogenotartrate, hydrochloride or sulfate.   5. Preparation according to any one of the preceding claims,   characterized in that the nicotine salt is present in a unit dose of about 0.86 to 1.72 milligrams, thereby providing a free base level of nicotine   approximately 0.3 to 0.6 milligrams.   6. Preparation according to any one of the preceding claims,   characterized in that it contains sufficient base to maintain a pH in the mouth of the user of at least 8.9 for at least 5 minutes after taking the tablet.   7. Preparation according to any one of the preceding claims,   characterized in that it is produced by granulating the nicotine salt by dry mixing it with a granulating agent, then mixing the granulated nicotine salt with the base of dry powder and with one or more tableting ingredients dry powder and compressing the mixture to form individual tablets.