CA2109895A1 - Nicotine containing oral preparation - Google Patents
Nicotine containing oral preparationInfo
- Publication number
- CA2109895A1 CA2109895A1 CA002109895A CA2109895A CA2109895A1 CA 2109895 A1 CA2109895 A1 CA 2109895A1 CA 002109895 A CA002109895 A CA 002109895A CA 2109895 A CA2109895 A CA 2109895A CA 2109895 A1 CA2109895 A1 CA 2109895A1
- Authority
- CA
- Canada
- Prior art keywords
- lozenge
- nicotine
- base
- group
- alkaloid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A24—TOBACCO; CIGARS; CIGARETTES; SIMULATED SMOKING DEVICES; SMOKERS' REQUISITES
- A24B—MANUFACTURE OR PREPARATION OF TOBACCO FOR SMOKING OR CHEWING; TOBACCO; SNUFF
- A24B15/00—Chemical features or treatment of tobacco; Tobacco substitutes, e.g. in liquid form
- A24B15/10—Chemical features of tobacco products or tobacco substitutes
- A24B15/16—Chemical features of tobacco products or tobacco substitutes of tobacco substitutes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/465—Nicotine; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
- A61K9/0058—Chewing gums
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2/00—Processes or devices for granulating materials, e.g. fertilisers in general; Rendering particulate materials free flowing in general, e.g. making them hydrophobic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Abstract
A method of making a lozenge for use as a oral smoking substitute comprising the steps of:
(i) forming granules by wet massing a strong base with granulating ingredients, and (ii) cold compressing the granules with a composition comprising an alkaloid selected from the group consisting of nicotine and pharmaceutically acceptable salts of nicotine to form a lozenge.
(i) forming granules by wet massing a strong base with granulating ingredients, and (ii) cold compressing the granules with a composition comprising an alkaloid selected from the group consisting of nicotine and pharmaceutically acceptable salts of nicotine to form a lozenge.
Description
R7~ oouND OF THE l~.vhr.~lON
This invention relates to nicotine containing oral preparations and to a method for their preparation. Smoking is now recognized as constituting a major health hazard. Many smokers have great difficulty in giving up smoking, even when recommended to do so on medical advice.
Nicotine (I) can be toxic; 40 mg has been recorded as a lethal dose. Typical cigarettes however contain about 1 mg of nicotine and at this dosage level it is not dangerous but gives a pleasurable sensation to users.
< ~ CH3 Attempts have been made to produce oral preparations which contain nicotine and which enable the user to enjoy the pleasurable effects of nicotine absorption without the hazards of smoking. One of the problems in producing nicotine-containing preparations is in controlling the release of the nicotine.
Nicotine is only absorbed buccally when in the form of the free 21098g5 base. The pH of saliva is generally acid, but varies widely according to food and drink recently consumed.
According to one aspect of the present invention, there is provided a smoking substitute preparation comprising nicotine in the form of pharmaceutically acceptable salt and a strong base which is sufficiently strong and present in sufficient amount to raise the pH within the user's mouth to at least 8.5 and preferably more than 8.9 thereby releasing the free nicotine base.
Provided that the strong base is present in an amount such as to raise the pH to about 8.9 or more, eg. to a pH in the range of 8.5 of 8.9 to about 10, this will ensure that approximately 90% of available nicotine is converted to the free base form and can therefore be buccally absorbed. The preparation may be formulated with buffering agents so that the pH developed within the user's mouth is buffered to a suitable level, eg. about 8.9 to 10.
The nicotine can be in the form of a pharmaceutically acceptable salt such as nicotine hydrogen tartrate, since the free nicotine base is volatile and would escape from a tabletted or lozenge preparation. The term lozenge hereinafter embraces tablets and other solid presentations. However, when the tablet or 102enge in accordance with the invention is placed in the mouth and starts to dissolve, the pH is raised to at least about 8.5 preferably about 8.9 because of the presence of the strong base and this converts the nicotine salt to free base, so that it is steadily absorbed in the buccal cavity.
As an alternative to the acid tartrate we may use other pharmaceutically acceptable salts such as hydrochloride or sulphate.
The free base is preferably an alkali metal carbonate, eg. sodium or potassium carbonate.
The free base is preferably formulated with suitable diluents or tabletting aids so that it can be formed into a tablet or lozenge by direct compression of the ingredients. The preparation therefore preferably includes directly compressible sugars. By varying the amounts or proportions of the sugar/xanthan gum/lactose, various disintegration times, and hence nicotine release times, between three and seven or ten minutes can be obtained.
Alternatively, a tablet or lozenge can be made from preparations in accordance with the invention by compression of a granule with other directly compressible components. In order to ensure a sustained pH of above 8.9 towards the end of the dissolving time, ie. at least about 3 minutes preferably about 5 minutes, 7 minutes or 10 minutes after taking the tablet, a proportion of the alkali metal carbonate can be granulated, eg. by wet massing, with other materials, such as lactose, sugar and fat-reduced cocoa powder, to produce a core granule which will release the alkali metal carbonate as it dissolves. This embodiment is illustrated in Example 3. The granules can be mixed with the nicotine containing material to give a homogeneous material but without the base being in intimate contact with the alkaloid. The granules could be in an outer sheath or in an inner core so as to give sequential release.
The tablet/lozenge may be flavoured as necessary, for example, with peppermint, vanilla, aniseed, chocolate, chocolate orange or liquorice. In addition, the tablet or lozenge may be colored with conventional, pharmaceutically acceptable food coloring agents.
The nicotine salt is normally present in the tablet or lozenge in an amount of between about .86 to 1.72 mg, thus providing a dosage unit of nicotine base of between .3 and .6 mg.
The following examples will illustrate formulations in accordance with the invention.
The raw materials set out in the following formulations were mixed and compressed into tablets using a conventional tabletting machine.
Example I
Raw Material % Grams Per tablet Icing Sugar 15.42 0.03700 Keltrol F (xanthan gum) 2.00 0.00480 Aerosil 200 0.20 0.00048 Ludipress (modified lactose)33.55 0.08051 Microtal DCE (sugar) 40.0 0.09600 Magnesium Stearate 0.50 0.00120 Stearic acid 1.00 0.00240 Peppermint F8554 2.80 0.00672 Nicotine hydrogen tartrate 0.37 0.00089 Sodium carbonate anhyd4.17 0.01000 Total: 100.00 0.24 Example II
Raw Material % Grams ~er tablet Icing Sugar 15.35 0.03700 Keltrol F (xanthan gum) 1.99 0.00480 Aerosil 200 0.20 0.00048 Ludipress (modified lactose)30.75 0.07411 Dipac (sugar) 39.84 0.09600 Magnesium Stearate 0.50 0.00120 Stearic acid 1.00 0.00240 Chocolate orange F37652.49 0.00600 Syloid 74 2.99 0.00720 Nicotine hydrogen tartrate 0.74 0.00178 Sodium carbonate anhyd4.15 0.01000 Total: 100.00 0.24097 Note: Microtal and Dipac are trade names for directly compressible sugars Example III
Raw Matqrial % Grams per tablet Granules Icing Sugar 48.97 0.11876 Lactose 26.70 0.06476 Avicel 3.87 0.00940 Liquorice powder 4.45 0.01079 Cocoa powder (fat reduced) 6.67 0.01619 ~ -- 6 Acacia 0.80 0.00194 Sodium carbonate anhyd 2.06 0.00500 Other Materials Magnesium stearate 1.07 0.00260 Anise oil 0.89 0.00216 Vanillin 0.03 0.00008 Syloid 244 0.64 0.00156 Peppermint F8554 1.29 0.00312 Nicotine hydrogen tartrate 0.49 0.00119 Sodium carbonate anhyd 2.06 0.00500 Total: 1.2 0.24254 Thus it is apparent that there has been provided accordance with the invention a nicotine containing oral preparation that fully satisfies the objects, aims and advantages set forth above. While the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art in light of the foregoing description.
Accordingly, it is intended to embrace all such alternatives, modifications and variations as fall within the spirit and broad scope of the invention.
This invention relates to nicotine containing oral preparations and to a method for their preparation. Smoking is now recognized as constituting a major health hazard. Many smokers have great difficulty in giving up smoking, even when recommended to do so on medical advice.
Nicotine (I) can be toxic; 40 mg has been recorded as a lethal dose. Typical cigarettes however contain about 1 mg of nicotine and at this dosage level it is not dangerous but gives a pleasurable sensation to users.
< ~ CH3 Attempts have been made to produce oral preparations which contain nicotine and which enable the user to enjoy the pleasurable effects of nicotine absorption without the hazards of smoking. One of the problems in producing nicotine-containing preparations is in controlling the release of the nicotine.
Nicotine is only absorbed buccally when in the form of the free 21098g5 base. The pH of saliva is generally acid, but varies widely according to food and drink recently consumed.
According to one aspect of the present invention, there is provided a smoking substitute preparation comprising nicotine in the form of pharmaceutically acceptable salt and a strong base which is sufficiently strong and present in sufficient amount to raise the pH within the user's mouth to at least 8.5 and preferably more than 8.9 thereby releasing the free nicotine base.
Provided that the strong base is present in an amount such as to raise the pH to about 8.9 or more, eg. to a pH in the range of 8.5 of 8.9 to about 10, this will ensure that approximately 90% of available nicotine is converted to the free base form and can therefore be buccally absorbed. The preparation may be formulated with buffering agents so that the pH developed within the user's mouth is buffered to a suitable level, eg. about 8.9 to 10.
The nicotine can be in the form of a pharmaceutically acceptable salt such as nicotine hydrogen tartrate, since the free nicotine base is volatile and would escape from a tabletted or lozenge preparation. The term lozenge hereinafter embraces tablets and other solid presentations. However, when the tablet or 102enge in accordance with the invention is placed in the mouth and starts to dissolve, the pH is raised to at least about 8.5 preferably about 8.9 because of the presence of the strong base and this converts the nicotine salt to free base, so that it is steadily absorbed in the buccal cavity.
As an alternative to the acid tartrate we may use other pharmaceutically acceptable salts such as hydrochloride or sulphate.
The free base is preferably an alkali metal carbonate, eg. sodium or potassium carbonate.
The free base is preferably formulated with suitable diluents or tabletting aids so that it can be formed into a tablet or lozenge by direct compression of the ingredients. The preparation therefore preferably includes directly compressible sugars. By varying the amounts or proportions of the sugar/xanthan gum/lactose, various disintegration times, and hence nicotine release times, between three and seven or ten minutes can be obtained.
Alternatively, a tablet or lozenge can be made from preparations in accordance with the invention by compression of a granule with other directly compressible components. In order to ensure a sustained pH of above 8.9 towards the end of the dissolving time, ie. at least about 3 minutes preferably about 5 minutes, 7 minutes or 10 minutes after taking the tablet, a proportion of the alkali metal carbonate can be granulated, eg. by wet massing, with other materials, such as lactose, sugar and fat-reduced cocoa powder, to produce a core granule which will release the alkali metal carbonate as it dissolves. This embodiment is illustrated in Example 3. The granules can be mixed with the nicotine containing material to give a homogeneous material but without the base being in intimate contact with the alkaloid. The granules could be in an outer sheath or in an inner core so as to give sequential release.
The tablet/lozenge may be flavoured as necessary, for example, with peppermint, vanilla, aniseed, chocolate, chocolate orange or liquorice. In addition, the tablet or lozenge may be colored with conventional, pharmaceutically acceptable food coloring agents.
The nicotine salt is normally present in the tablet or lozenge in an amount of between about .86 to 1.72 mg, thus providing a dosage unit of nicotine base of between .3 and .6 mg.
The following examples will illustrate formulations in accordance with the invention.
The raw materials set out in the following formulations were mixed and compressed into tablets using a conventional tabletting machine.
Example I
Raw Material % Grams Per tablet Icing Sugar 15.42 0.03700 Keltrol F (xanthan gum) 2.00 0.00480 Aerosil 200 0.20 0.00048 Ludipress (modified lactose)33.55 0.08051 Microtal DCE (sugar) 40.0 0.09600 Magnesium Stearate 0.50 0.00120 Stearic acid 1.00 0.00240 Peppermint F8554 2.80 0.00672 Nicotine hydrogen tartrate 0.37 0.00089 Sodium carbonate anhyd4.17 0.01000 Total: 100.00 0.24 Example II
Raw Material % Grams ~er tablet Icing Sugar 15.35 0.03700 Keltrol F (xanthan gum) 1.99 0.00480 Aerosil 200 0.20 0.00048 Ludipress (modified lactose)30.75 0.07411 Dipac (sugar) 39.84 0.09600 Magnesium Stearate 0.50 0.00120 Stearic acid 1.00 0.00240 Chocolate orange F37652.49 0.00600 Syloid 74 2.99 0.00720 Nicotine hydrogen tartrate 0.74 0.00178 Sodium carbonate anhyd4.15 0.01000 Total: 100.00 0.24097 Note: Microtal and Dipac are trade names for directly compressible sugars Example III
Raw Matqrial % Grams per tablet Granules Icing Sugar 48.97 0.11876 Lactose 26.70 0.06476 Avicel 3.87 0.00940 Liquorice powder 4.45 0.01079 Cocoa powder (fat reduced) 6.67 0.01619 ~ -- 6 Acacia 0.80 0.00194 Sodium carbonate anhyd 2.06 0.00500 Other Materials Magnesium stearate 1.07 0.00260 Anise oil 0.89 0.00216 Vanillin 0.03 0.00008 Syloid 244 0.64 0.00156 Peppermint F8554 1.29 0.00312 Nicotine hydrogen tartrate 0.49 0.00119 Sodium carbonate anhyd 2.06 0.00500 Total: 1.2 0.24254 Thus it is apparent that there has been provided accordance with the invention a nicotine containing oral preparation that fully satisfies the objects, aims and advantages set forth above. While the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art in light of the foregoing description.
Accordingly, it is intended to embrace all such alternatives, modifications and variations as fall within the spirit and broad scope of the invention.
Claims (18)
1. A method of making a lozenge for use as a oral smoking substitute comprising the steps of:
(i) forming granules by wet massing a strong base with granulating ingredients, and (ii) cold compressing the granules with a composition comprising an alkaloid selected from the group consisting of nicotine and pharmaceutically acceptable salts of nicotine to form a lozenge.
(i) forming granules by wet massing a strong base with granulating ingredients, and (ii) cold compressing the granules with a composition comprising an alkaloid selected from the group consisting of nicotine and pharmaceutically acceptable salts of nicotine to form a lozenge.
2. The method of claim 1 wherein the amount of said alkaloid per lozenge is in the range of about 0.3 to about 0.6 mg calculated as nicotine free base.
3. The method of claim 1 wherein said nicotine salt is selected from the group consisting of nicotine hydrochloride and nicotine sulphate.
4. The method of claim 1 wherein said strong base is selected from the group consisting of sodium carbonate and potassium carbonate.
5. The method of claim 4 wherein the amount of said base per lozenge is about 0.5 to about 1.5 mmol.
6. The method of claim 1 wherein at least one of the group selected from the granules and the alkaloid containing composition includes a flavouring selected from the group consisting of peppermint, vanilla, aniseed, chocolate, chocolate orange and liquorice.
7. The method of claim 1 wherein the strong base is granulated with a granulating ingredient selected from the group consisting of lactose, sucrose and fat reduced cocoa powder.
8. The method of any one of the preceding claims, wherein said granules are formed into a sheath surrounding a core comprising said alkaloid containing material.
9. A lozenge for use as an oral smoking substitute, the lozenge comprising an outer sheath comprising an amount of a strong base sufficient to raise the pH of the buccal cavity of a user to at least 8.5 surrounding a core comprising an alkaloid selected from nicotine and pharmaceutically acceptable salts of nicotine.
10. The lozenge of claim 9 comprising about 0.5 to about 1.5 mmol of a strong base selected from sodium carbonate and potassium carbonate and about 0.3 to about 0.6 mg calculated as nicotine free base of alkaloid.
11. A lozenge for use as an oral smoking substitute comprising a pharmaceutically acceptable salt of nicotine a buffered base capable of buffering the pH in the buccal cavity of a user to a level between about 8.5 and 10 and a directly compressible component enabling the formulation to be tabletted by direct compression.
12. The lozenge of claim 11 wherein the said base raises the pH of the buccal cavity of a user to at least about 8.5 for at least about three minutes.
13. The lozenge of claim 12 wherein the said base raises the pH of the buccal cavity to at least about 8.5 for not more than about seven minutes.
14. The lozenge of claim 11 wherein said base is selected from the group consisting of sodium carbonate and potassium carbonate.
15. The lozenge of claim 14 wherein the amount of said base is in the range of about 0.5 to about 1.5 mmol.
16. The lozenge of claim 11 wherein the amount of said alkaloid is about 0.3 to about 0.6 mg calculated as nicotine free base.
17. The lozenge of claim 11 wherein said base is capable of buffering the pH of the buccal cavity to at least 8.9.
18. The lozenge of claim 11 further comprising a flavouring selected from peppermint, vanilla, aniseed, chocolate, chocolate orange and liquorice.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002109895A CA2109895A1 (en) | 1993-11-24 | 1993-11-24 | Nicotine containing oral preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002109895A CA2109895A1 (en) | 1993-11-24 | 1993-11-24 | Nicotine containing oral preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2109895A1 true CA2109895A1 (en) | 1995-05-25 |
Family
ID=4152530
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002109895A Abandoned CA2109895A1 (en) | 1993-11-24 | 1993-11-24 | Nicotine containing oral preparation |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2109895A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6344222B1 (en) | 1998-09-03 | 2002-02-05 | Jsr Llc | Medicated chewing gum delivery system for nicotine |
| US6358060B2 (en) | 1998-09-03 | 2002-03-19 | Jsr Llc | Two-stage transmucosal medicine delivery system for symptom relief |
| US8642016B2 (en) | 2006-07-21 | 2014-02-04 | Jsrnti, Llc | Medicinal delivery system, and related methods |
-
1993
- 1993-11-24 CA CA002109895A patent/CA2109895A1/en not_active Abandoned
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6344222B1 (en) | 1998-09-03 | 2002-02-05 | Jsr Llc | Medicated chewing gum delivery system for nicotine |
| US6358060B2 (en) | 1998-09-03 | 2002-03-19 | Jsr Llc | Two-stage transmucosal medicine delivery system for symptom relief |
| US8642016B2 (en) | 2006-07-21 | 2014-02-04 | Jsrnti, Llc | Medicinal delivery system, and related methods |
| US10799449B2 (en) | 2006-07-21 | 2020-10-13 | Jsrnti, Llc | Medicinal delivery system and related methods |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |