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Nicotine replacement therapy (NRT) can help smokers to quit smoking. Nicotine chewing gum has attracted the attention from pharmaceutical industries to offer it to consumers as an easily accessible NRT product. However, the bitter taste of such gums may compromise their acceptability by patients. This study was, therefore, designed to develop 2 and 4 mg nicotine chewing gums of pleasant taste, which satisfy the consumers the most. Nicotine, sugar, liquid glucose, glycerin, different sweetening and taste-masking agents, and a flavoring agent were added to the gum bases at appropriate temperature. The medicated gums were cut into pieces of suitable size and coated by acacia aqueous solution (2% w/v), sugar dusting, followed by acacia-sugar-calcium carbonate until a smooth surface was produced. The gums' weight variation and content uniformity were determined. The release of nicotine was studied in pH 6.8 phosphate buffer using a mastication device which simulated the mastication of chewing gum in human. The Latin Square design was used for the evaluation of organoleptic characteristics of the formulations at different stages of development. Most formulations released 79-83% of their nicotine content within 20 min. Nicotine-containing sugar-coated gums in which aspartame as sweetener and cherry and eucalyptus as flavoring agents were incorporated (i.e. formulations F(19-SC) and F(20-SC), respectively) had optimal chewing hardness, adhering to teeth, and plumpness characteristics, as well as the most pleasant taste and highest acceptability to smokers. Taste enhancement of nicotine gums was achieved where formulations comprised aspartame as the sweetener and cherry and eucalyptus as the flavoring agents. Nicotine gums of pleasant taste may, therefore, be used as NRT to assist smokers quit smoking.
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Advanced Biomedical Research | October - December 2012 | Vol 1 | Issue 4 1
Background: Nicotine replacement therapy (NRT) can help smokers to quit smoking. Nicotine chewing gum
has attracted the attention from pharmaceutical industries to offer it to consumers as an easily accessible
NRT product. However, the bitter taste of such gums may compromise their acceptability by patients. This
study was, therefore, designed to develop 2 and 4 mg nicotine chewing gums of pleasant taste, which
satisfy the consumers the most.
Materials and Methods: Nicotine, sugar, liquid glucose, glycerin, different sweetening and taste-masking
agents, and a flavoring agent were added to the gum bases at appropriate temperature. The medicated
gums were cut into pieces of suitable size and coated by acacia aqueous solution (2% w/v), sugar dusting,
followed by acacia–sugar–calcium carbonate until a smooth surface was produced. The gums’ weight
variation and content uniformity were determined. The release of nicotine was studied in pH 6.8 phosphate
buffer using a mastication device which simulated the mastication of chewing gum in human. The Latin
Square design was used for the evaluation of organoleptic characteristics of the formulations at different
stages of development.
Results: Most formulations released 79–83% of their nicotine content within 20 min. Nicotine-containing
sugar-coated gums in which aspartame as sweetener and cherry and eucalyptus as flavoring agents were
incorporated (i.e. formulations F19-SC and F20-SC, respectively) had optimal chewing hardness, adhering to
teeth, and plumpness characteristics, as well as the most pleasant taste and highest acceptability to smokers.
Conclusion: Taste enhancement of nicotine gums was achieved where formulations comprised aspartame
as the sweetener and cherry and eucalyptus as the flavoring agents. Nicotine gums of pleasant taste may,
therefore, be used as NRT to assist smokers quit smoking.
Key Words: Nicotine chewing gum, nicotine replacement therapy, nicotine addiction, smoking cessation
Address for correspondence:
Dr. Abolfazl Aslani, Department of Pharmaceucs, School of Pharmacy and Pharmaceucal Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
E-mail: aslani@pharm.mui.ac.ir
Received: 20.02.2012, Accepted: 09.07.2012
Abstract
Design, formulation and evaluation of nicotine chewing gum
Abolfazl Aslani, Sahar Raei
Department of Pharmaceucs, School of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical
Sciences, Isfahan, Iran
Original Article
Access this article online
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Website:
www.advbiores.net
DOI:
10.4103/2277-9175.100175
INTRODUCTION
Tobacco use through cigarette smoking is the
leading avoidable cause of death in the world; it
kills almost 4 million people each year. According
to the World Health Organization, 10 million
smokers will die per year by 2030.[1] There are over
4000 chemicals in cigarette smoke,[2] including
43 carcinogenic compounds and 400 other toxins
How to cite this article: Aslani A, Raei S. Design, formulation and evaluation of nicotine chewing gum. Adv Biomed Res 2012;1:57.
Copyright: © 2012 Aslani. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction
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Aslani and Rafiei: Formulation of nicotine chewing gum
2 Advanced Biomedical Research | October - December 2012 | Vol 1 | Issue 4
such as nicotine, tar, carbon monoxide, as well as
formaldehyde, ammonia, hydrogen cyanide, arsenic,
and dichlorodiphenyltrichloroethane (DDT).
[3] Nicotine
is the main active component in cigarette that
reinforces individual smoking behavior. However,
there are other ingredients of tobacco and not
nicotine that lead to the mortality and morbidity.[4]
People become dependent on the nicotine in cigarette
because it raises the levels of special chemicals, such
as dopamine and norepinephrine, in their brains.[5]
Smoking cessation at any age decreases the morbidity.
When people stop smoking, the levels of those
chemicals fall, and reactions of body appear as nicotine
withdrawal syndrome such as craving for tobacco,
irritability, nervousness, difficulty concentrating,
impatience, insomnia, and increased appetite.[6]
Nicotine replacement therapy (NRT) can help smokers
to quit smoking by replacing some of the nicotine
generally gained from cigarettes.[7] It decreases many
of the physiological and psychomotor withdrawal
symptoms usually experienced after smoking cessation
and may thus enhance the chance of remaining
abstinent.[8]
NRT products include chewing gum, transdermal
patch, nasal spray, oral inhaler, and tablet.[4] The first
product of NRT to become widely accessible was the
chewing gum.[8] The Food and Drug administration
(FDA) confirmed the prescription use of nicotine
chewing gum as smoking cessation aid in 1984 and
its nonprescription sale in 1995.[6]
The chewing gum is one of the new methods of oral
transmucosal drug delivery and is a useful tool for
systemic drug delivery.[9] Advantages of chewing
gum over conventional drug delivery system include:
Rapid onset of action, high bioavailability, easy
consumption without the need of water, higher patient
compliance, and fewer side effects like dry mouth and
decrease in toxicity.[10] Formulations of medicated
chewing gums may include active components, gum
base, filler, softeners, sweetening agents, flavoring
agents, and emulsifiers.[11] Medicated chewing gums
are formulated to release the majority of their
active component within 20–30 min. Factors such as
intensity of chewing the gum and amount of saliva
produced influence the drug release and absorption
in the buccal cavity.[12]
In general, decrease in drug concentration upon
dilution with saliva and its disappearance from buccal
cavity due to unwanted ingestion are the disadvantages
of medicated chewing gums. Chewing gums as a drug
delivery system are, however, functional for medicines
such as nicotine, caffeine, fluoride, dimenhydrinate,
chlorhexidine, etc.[11]
Nicotine chewing gum is currently available in the
market either as 2 or 4 mg preparations. The gums
release a controlled amount of nicotine in mouth
that is absorbed directly through the buccal mucosa,
producing nicotine plasma concentrations which are
about half that is produced by smoking a cigarette.[8]
A limitation of commercially available nicotine gums
is their slow rate of nicotine release and consequently
the slow onset of their therapeutic effects.
The unpleasant taste of nicotine gums is, however,
a major challenge with respect to the patients’
acceptance and compliance with suggested dosing
regimens.[13] Thus, the present study was carried
out to develop nicotine gums with improved taste
and quality as a favorable dosage form for NRT. We
formulated the gums using nicotine hydrogen tartrate
due to its faster release rate. This may produce a
more rapid onset of craving relief, and thus greater
clinical benefits.[14]
MATERIALS AND METHODS
Chemicals
Nicotine tartrate was purchased from Sigma-Aldrich
Co. LLC. (Berlin, Germany). Elvasti, 487, Stick, and
Fruit C gum bases were obtained from Gilan Ghoot
Company, (Rasht, Iran). Flavors of eucalyptus,
peppermint, banana, cola, and cinnamon were gifted
by Goltash Company, (Isfahan, Iran), and flavors
of cherry, tutti-frutti and raspberry by Farabi
Pharmaceutical Company, (Isfahan, Iran). Sugar,
glycerin, sodium saccharin, aspartame, stevia, zinc
acetate, sodium acetate, and sodium chloride were of
pharmaceutical grade.
Preparation of nicotine chewing gum
The nicotine gum was formulated using the gum
bases, sugar, liquid glucose, glycerin, a sweetener
(aspartame, stevia, liquorice, or sodium saccharin),
a taste-masking material (zinc acetate, sodium
acetate, or sodium chloride), and a flavoring agent.
The mixture of gum bases was softened at 60°C.
Nicotine tartrate, sugar, liquid glucose, glycerin, and
other ingredients [Table 1] were added to the base
to which was finally added the flavor at 40°C. The
uniform mixture was cut into the pieces of suitable
shape and size and kept at room temperature for 48
h [Table 1]. The medicated gums so prepared were
coated by acacia aqueous solution (2% w/v). Sugar
dusting followed by acacia–sugar–calcium carbonate
coating was carried out until a smooth surface was
produced.
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Aslani and Rafiei: Formulation of nicotine chewing gum
Advanced Biomedical Research | October - December 2012 | Vol 1 | Issue 4 3
All formulations were preliminary investigated for
considering the effect of different flavoring agents
on masking the bitter taste of nicotine. Selected
formulations according to organoleptic characteristics
were prepared by using flavoring of cherry, eucalyptus,
peppermint, banana, cola, tutti-frutti, and raspberry
[Table 2].
Weight variation
Ten chewing gums of each formulation were weighed.
The average weight and standard deviation were
calculated.[15]
Uniformity of content
Ten nicotine gums were selected randomly.[16]
Each gum was first dissolved in 50 ml chloroform.
Phosphate buffer pH 6.8 was then used to extract
drug into the aqueous phase. The amount of nicotine
was determined by measuring the drug absorbance at
260.8 nm using a Shimadzu UV-1240 model UV-visible
spectrophotometer. The experiment was repeated
three times. The standard curve of nicotine tartrate
was linear [y = 0.0198x + 0.0089 (R2 = 0.9995)] at
concentrations ranging 5–60 µg/ml.
In vitro
drug release
A mastication device which simulated the mastication
of chewing gum in human was used to perform the
drug release study. The device consisted of a piston
which strokes the gum (60 strokes/min) at different
points on a random base and a chamber which holds
the gum and the release medium (pH 6.8 phosphate
buffer). Water (37°C) was circulated through a jacket
around the receiver chamber to simulate the in vivo
temperature.[17]
Aliquots of 1 ml were removed at 0, 5, 10, 15, 20, 25,
30, and 45 min, and their absorbance were measured
at 260.8 nm, as described before. The test was repeated
three times.
Evaluating the organoleptic characteristics of nicotine
chewing gums
The Latin Square design was used for the preliminary
evaluation of organoleptic characteristics of the
formulations. Ten smokers were asked to chew each
gum (F1–F18 formulations) for 20 min and express their
opinions about chewing hardness, gum adhering to
teeth, the plumpness, and the taste, according to the
Likert scale of 1–5 (very poor = 1, poor = 2, average =
3, good = 4, and excellent = 5). The subjects were asked
Table 1: Formulations of nicotine chewing gum with different ingredients
Ingredients (mg) Formulations
F1F2F3F4F5F6F7F8F9F10 F11 F12 F13 F14 F15 F16 F17 F18
Nicotine 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 4 4
Gum bases
Elvasti 12 0 63 189 12 6 70 70 70 70 70 70 70 70 70 70 70 70 70 70
487 - 24 72 48 70 70 70 70 70 70 70 70 70 70 70 70 70 70
Stick - 24 72 48 70 70 70 70 70 70 70 70 70 70 70 70 70 70
Fruit C - 9 27 18 70 70 70 70 70 70 70 70 70 70 70 70 70 70
Sugar 532 532 532 550 500 500 500 500 500 500 500 500 500 500 500 500 500 500
Liquid glucose 15 0 15 0 15 0 218 220 200 200 200 200 200 200 200 200 200 200 200 200 200
Glycerol 16 16 16 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20
Aspartame - - - - - - - - - - - - - 2 2 2 2 3
Sodium saccharin - - - 2 2 - - - - - - - - - - - - -
Liquorice - - - - - 20 20 20 20 20 20 20 20 20 20 - - -
Stevia - - - - - - 2 10 10 10 10 10 5 - - - - -
Sodium chloride - - - - - - - - - - 10 10 - - - - - -
Sodium acetate - - - - - - 10 5 20 - - - - - - - - -
Zinc acetate - - - - - - - - - 10 - - 10 20 - - - -
Cola - - - - - - 10 - - - - - - - - - - -
Banana 10 10 10 - - - - - - - - - - - - - - -
Peppermint - - - 10 - - - - - - - - - - - - - -
Eucalyptus - - - - 10 10 - - - - - - - - - - - -
Cinnamon - - - - - - - 10 10 10 10 15 15 15 15 15 15 15
Table 2: Formulations of nicotine chewing gum by altering the
flavoring agent in the formulation F16
Formulation Flavoring agent
F19 Cherry
F20 Eucalyptus
F21 Peppermint
F22 Banana
F23 Cola
F24 Tutti-frutti
F25 Raspberry
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Aslani and Rafiei: Formulation of nicotine chewing gum
4 Advanced Biomedical Research | October - December 2012 | Vol 1 | Issue 4
to rinse their mouths with water and wait for 20 min
before examining the next formulation.
Further development of formulations was performed
by altering the flavoring agent in the formulation
F16, indicated to be the most acceptable gum in the
preliminary evaluation [Table 2]. A panel test consisting
of 20 smokers also was used in the same manner as
previously explained to evaluate acceptability of the
formulations. In the last stage, two formulations, (F19,
F20), shown to be more acceptable to patients in the
previous study, were sugar-coated and given to a new
group of 30 smokers and evaluated as before.
RESULTS
Chewing gums weight variation and nicotine content
Weight variation of gums was within the USP-
recommended limit of ±5%. The mean drug content
was 1.94 ± 0.085 for 2 mg and 3.87 ± 0.125 for 4 mg
nicotine chewing gums, all satisfying the criteria
commonly required by USP for solid dosage forms.
In vitro drug release from chewing gums
The release of nicotine from gum bases is shown in
Figure 1. About 83% and 79% nicotine was released
after 20 min from 2 and 4 mg gum, respectively. The
drug release was, however, 92% and 93% from 2 and
4 mg formulations, respectively, after 45 min.
Evaluation of organoleptic characteristics of nicotine
chewing gum
Organoleptic characteristics of nicotine gums were
dependent on the ingredients used. F16 and F18
formulations (of 2 and 4 mg nicotine gums, respectively)
exhibited acceptable physical characteristics with
respect to chewing hardness, gum adhering to teeth,
the plumpness, and the overall taste in preliminary
evaluations [Table 3]. Further modification of
formulation F16 using different flavoring agents
indicated that cherry and eucalyptus (F19 and F20)
Figure 1: In vitro
release of nicotine from 2 and 4 mg chewing gum in
pH 6.8 phosphate buffer at 37°C
were most efficacious in removing the bitter taste of
nicotine gums [Table 4]. Sugar coating improved the
appearance of gums; however, its effect on the taste
was only marginal [Table 5].
Table 3: Organoleptic characteristics of different nicotine
chewing gums
Formulation Chewing
hardness
Plumpness Adhering to
teeth
Taste*
F1Very hard Little No 1
F2Hard Little No 1
F3Hard Much No 1
F4Hard Suitable No 1.6
F5Suitable Suitable No 1.7
F6Suitable Suitable No 1.7
F7Suitable Suitable No 1.8
F8Suitable Suitable No 1.7
F9Suitable Suitable No 1.9
F10 Suitable Suitable Yes 2.5
F11 Suitable Suitable No 1.7
F12 Suitable Suitable No 1.8
F13 Suitable Suitable No 2.6
F14 Suitable Suitable No 3.1
F15 Suitable Suitable No 3.0
F16 Suitable Suitable No 3.5
F17 Suitable Suitable No 3.1
F18 Suitable Suitable No 3.5
*The taste was determined by 10 smokers using the Likert scale of 1–5
(Very poor = 1, Poor = 2, Average = 3, Good = 4, and Excellent = 5)
Table 4: Taste evaluation of formulations F16 and F19 –F25 with
different flavoring agents in nicotine gum formulations
Formulations*Score**
1 2 3 4 5 Mean
F16 2 5 8 5 - 2.8
F19 - 2 5 13 - 3.55
F20 1 2 6 11 - 3.35
F21 6 5 8 1 - 2.2
F22 7 9 3 1 - 1.9
F23 12 4 4 - - 1. 6
F24 2 7 8 3 - 2.6
F25 3 4 12 1 - 2.55
*The taste was determined by 20 smokers using the Likert scale of 1–5 (Very
poor = 1, Poor = 2, Average = 3, Good = 4, and Excellent = 5) **The flavoring
agents used in F16 and F19 –F25 formulations were cinnamon, cherry, eucalyptus,
peppermint, banana, cola, tutti-frutti, and raspberry, respectively
Table 5: The taste-masking effects of cherry or eucalyptus as
flavoring agent in nicotine sugar-coated gum formulations
Scores*Formulations**
F19- SC F20-SC
1 0 1
2 2 3
3 8 10
419 16
5 1 -
Mean 3.63 3.37
The taste was determined by 30 smokers using the Likert scale of 1–5 (Very poor
= 1, Poor = 2, Average = 3, Good = 4, and Excellent = 5) **The flavoring agents
used in F19 and F20 formulations were cherry and eucalyptus, respectively
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Aslani and Rafiei: Formulation of nicotine chewing gum
Advanced Biomedical Research | October - December 2012 | Vol 1 | Issue 4 5
DISCUSSION
Nicotine gums can be considered as a dosage form which
is provided to smokers, helping them quit smoking. To
be demanded by patients, such medicated gums are
required to have an optimal chewing volume, a long-
lasting taste, anti-adherent properties to the teeth,
and suitable organoleptic properties. Formulation
F1 was very hard due to the nature of Elvasti base
used. Elvasti, Stick, 487, and Fruit C bases have
different hardness. Elvasti and Fruit C bases have
the highest and the lowest hardness, respectively.
In formulations F2–F4, by using three other bases,
hardness of gum became less, but it was not suitable
yet. In formulations F5–F25, softness and hardness of
gum was desirable. In this study, for providing nicotine
gum with suitable softness and hardness, equal ratios
of Elvasti, Stick, 487, and Fruit C bases were used,
but it is possible to use different ratios of these base
in other medicated and non-medicated chewing gums.
Sodium saccharin with a sweetening power of 300–600
times higher than sucrose, though reported to enhance
the effects of flavoring systems,[18] had little or no
effect on masking the bitter taste of nicotine gums
[Table 3] (F4 and F5). Liquorice, a sweetening agent
which is widely used in tobacco industry,[19] decreased
the bitterness of nicotine only slightly [Table 3]
(F6). Similarly, sodium salts were not efficacious in
masking the bitter taste [Table 3] (F7–F9 and F11–F12).
This was not in agreement with other reports on the
positive effects of sodium salts on the bitter taste
improvement.[20]
Zinc acetate in formulations F10 and F13–F14 had a
moderate effect in masking the bitterness of nicotine
[Table 3]. It seems that zinc influences oral perception
by eliciting the taste itself, interfering with the normal
function of a taste system, and eliciting astringency.[21]
In our study, aspartame exhibited the strongest effect
on modifying the bitter taste of nicotine gums [Table 3]
(F16–F18). The amount of aspartame used seemed to
be important too (compare F17 and F18) [Table 3]. The
effect of aspartame was, however, reduced where
other sweeteners were also added to the formulations
[Table 3] (F14, F15).
The effects of various flavoring agents investigated
through formulations F16 and F19–F25 [Table 4]
indicated that cherry and eucalyptus produced the
most pleasing taste (F19, F20). The overall effects of
sweeteners and flavoring agents on taste modification
seem to be dependent on the type of dosage form
as well as active and inactive ingredients used in
the formulation. While some have reported bitter
taste modification of chlorhexidine chewing gums by
aspartame, peppermint, and menthol,[17] others have
seen better effect with sorbitol and peppermint.[15]
However, in our study, peppermint showed an average
effect on taste masking (compare F21 vs. F19 and F20)
[Table 4]. Thus, it is rational to design and perform
taste-modification investigations on each medication
and dosage form independently.
Formulations F16 and F18 released 83% and 79% of
their nicotine content within 20 min, respectively.
This was in agreement with results obtained by
Morjaria et al. on nicotine chewing gums, marketed
as Pharmagum®S, Pharmagum®M, and Nicorette®.[22]
CONCLUSION
The results of this study showed that gum can be
a good carrier of nicotine. The best formulations
according to organoleptic characteristics were F16 and
F18 for 2 and 4 mg gum, respectively. Aspartame and
flavoring of cherry and eucalyptus were more effective
to eliminate the bitter taste of nicotine.
ACKNOWLEDGMENT
This study was supported by Isfahan University of Medical
Sciences as a thesis research project numbered 389366.
REFERENCES
1. Mitrouska I, Bouloukaki I, Siafakas NM. Pharmacological approaches to
smoking cessation. Pulm Pharmacol Ther 2007;20:220-32.
2. Bernhard D, Moser C, Backovic A, Wick G. Cigarette smoke--an aging
accelerator? Exp Gerontol 2007;42:160-5.
3. Quit Smoking Support.com. [Updated 2012 January]. Available from: http://
www. quit smoking support.com/whatsinit.htm.
4. Thomas E, Novotng TE, Cohen JC, Yarekli A, Sweanor D, Beyer J. Smoking
cessation and nicotine-replacement therapies. In Jha P, Chaloupka FJ,
editors. Tabacco control in developing countries. Oxford: Oxford University
Press; 2000. p. 287-307.
5. Yildiz D. Nicotine, its metabolism and an overview of its biological effects.
Toxicon 2004;43:619-32.
6. Karnath B. Smoking cessation. Am J Med 2002;112:399-405.
7. Kralikova E, Kozak JT, Rasmussen T, Gustavsson G, Houezec JL. Smoking
cessation or reduction with nicotine replacement therapy: A placebo-
controlled double blind trial with nicotine gum and inhaler. BMC Public
Health 2009;9:433.
8. Silagy C, Lancaster T, Stead L, Mant D, Fowler G. Nicotine replacement
therapy for smoking cessation (Review). Cochrane Database Syst Rev
2004;3:CD000146.
9. Madhav NV, Shakya AK, Shakya P, Singh K. Orotransmucosal drug delivery
systems: A review. J Control Release 2009;140:2-11.
10. Biradar SS, Bhagavti ST, Hukkeri VI, Rao KP, Gadad AP. Chewing gum
as a drug delivery system. Scientic Journal Articles 2005. Available from:
http://www.vipapharma.com/
11. Surana SA. Chewing gum: A friendly oral mucosal drug delivery system.
Int J Pharm Sci Rev Res 2010;4:68-71.
12. Rowe RC. By gum a buccal delivery system - Private prescription: A thought-
provoking tonic on the lighter side. Drug Discov Today 2003;8:617-8.
13. Britt DM, Cohen LM, Collins FL, Cohen ML. Cigarette smoking and
[Downloaded free from http://www.advbiores.net on Wednesday, September 28, 2016, IP: 89.67.131.146]
Aslani and Rafiei: Formulation of nicotine chewing gum
6 Advanced Biomedical Research | October - December 2012 | Vol 1 | Issue 4
chewing gum: Response to a laboratory-induced stressor. Health Psychol
2001;20:361-8.
14. Shiffman S, Cone EJ, Buchhalter AR, Henningeld JE, Rohay JM, Gitchell
GJ,
et al
. Rapid absorption of nicotine from new nicotine gum formulations.
Pharmacol Biochem Behav 2009;91:380-4.
15. Pandey S, Goyani M, Devmurari V. Development, in-vitro evaluation
and physical characterization of medicated chewing gum: Chlorhexidine
gluconate. Der Pharmacia Lettre 2009;1:286-92.
16. European Pharmacopoeia, 6st ed. Strasbourg: Directorate for the Quality
of Medicine and Health Care of the Council of Europe, 2009. p. 278.
17. Kolahi Kazerani G, Ghalyani P, Varshosaz J. A study on design, formulation
and effectiveness of chewing gum containing chlorhexidine gluconate in the
prevention of dental plaque. J Dent Tehran Univ Med Sci 2003;16:53-8.
18. Hoppu P. Saccharine sodium. In, Rowe RC, editor. Handbook of Source of Support: Nil, Conict of Interest: None declared.
pharmaceutical excipients, 6st ed. London: Pharmaceutical Press; 2009.
P. 608-9.
19. Liquorice. Wikipedia, the Free Encyclopedia. Available from: http://
en.wikipedia.org/wiki/Liquorice [Last Updated on 2012 Jan 27].
20. Ley JP. Masking bitter taste by molecules. Chem Percept 2008;1:58-77.
21. Keast RSJ. The effect of zinc on human taste perception. J Food Sci
2003;68:1871-7.
22. Morjaria Y, Irwin WJ, Barnett PX, Chan RS, Conway BR.
In vitro
release of
nicotine from chewing gum formulations. Dissolut Technol 2004;11:12-5.
[Downloaded free from http://www.advbiores.net on Wednesday, September 28, 2016, IP: 89.67.131.146]
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... This study highlighted the impact of each gum ingredient on the quality of the MCGs and demonstrated the feasibility of preparing chewing gums with up to 50% drug loading. 2005), or simply on molten pre-fabricated chewing gums (Al-Ghananeem et al., 2017;Aslani and Rafiei, 2012;Potineni and Peterson, 2008). Commercially available gum bases are made by combining a continuous water-soluble phase, consisting primarily of sugars, polyols, and sweeteners, with an insoluble discontinuous phase (Aslani and Rostami, 2015;Chaudhary and Shahiwala, 2010). ...
... Medicated chewing gums (MCGs) are solid preparations that consist primarily of a gum base that is intended to be chewed for a certain period of time, thereby providing a slow release of the medicine contained (Aslani and Rostami, 2015). Numerous publications on the formulation and characterization of MCGs and their applications in drug delivery are readily available (Al-Ghananeem et al., 2017;Aslani and Rafiei, 2012;Faraj et al., 2007;Jójárt et al., 2016;Jójárt et al., 2013;Kása et al., 2013;Morjaria et al., 2004;Na et al., 2005;Paradkar et al., 2016;Potineni and Peterson, 2008;Shete et al., 2015;Stojanov and Larsen, 2012). In the majority of the published works, however, the preparation of the MCGs rely on commercially available chewing gum bases such as Health-in-Gum® (Jójárt et al., 2016;Jójárt et al., 2013;Paradkar et al., 2016), Pharmagum® Morjaria et al., 2004;Shete et al., 2015), SMILY 2A® (Faraj et al., 2007;Na et al., accelerates the development of MCGs, it confines the formulator to few variables, such as the ratio between the drug and the base to modulate the properties of the resultant MCGs. ...
Article
Curcumin (CUR) chewing gums have potential therapeutic benefits to head and neck cancer patients. The objective of this work was to develop medicated chewing gums (MCGs) with high CUR loading and desirable mastication properties. This was accomplished by evaluating the effect of five gum ingredients: (X1) polyisobutene, (X2) polyvinyl acetate, (X3) wood rosin, (X4) wax, and (X5) CUR on the mechanical properties of the MCGs using a 25-run, five-factor, two-level D-Optimal mixture design. CUR MCGs were prepared by the conventional fusion method for making chewing gums. They were characterized by two-bites texture and uniaxial tension tests to generate force-displacement curves from which the cohesiveness (Y1), springiness (Y2), chewiness (Y3), compressibility (Y4), and resistance to extension (Y5), and extensibility (Y6) were measured. Observed responses were used to generate polynomial models correlating the independent with the dependent variables. Elasticity and stiffness of the gums were found to be readily impacted by PIB and CUR levels. Fitted models were then used to predict a gum composition that has comparable mechanical properties to commercially procured chewing gums. The optimized MCG was loaded with 50% of either CUR or CUR/SBE-β-CD inclusion complex and tested in vitro for drug release. Although no differences in mechanical properties were observed, substituting CUR with the inclusion complex was found to significantly enhance drug release. This study highlighted the impact of each gum ingredient on the quality of the MCGs and demonstrated the feasibility of preparing chewing gums with up to 50% drug loading.
... The scientific evidence and clinical guideline accept and recommend nicotine replacement therapy as the first choice for people seeking help to stop smoking (4). Many formulations for nicotine replacement therapy are currently developed and used such as transdermal patches (5)(6)(7)(8)(9), film-forming polymeric solutions (10,11), nasal sprays (12,13), chewing gums (14,15), oral inhalers (16,17), and tablets (18,19). The transdermal patch is the best dosage form for nicotine replacement therapy products compared with other dosage forms because it is widely and easily used to facilitate the cessation of smoking and is applied once a day, usually used at the same time each day. ...
Article
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Design of experiments is used to optimize ratios between deproteinized natural rubber latex, Eudragit® NM 30 D, and pectin for nicotine buccal film with dependent variables as moisture content, moisture uptake, and swelling index in simulated saliva 3 and 5 h. Mathematical models were linear for moisture content and moisture uptake, while swelling index in simulated saliva 3 and 5 h was a quadratic model. Optimized polymer ratio was 0.319:0.362:0.319, respectively. Experimental values were 13.17 ± 0.92%, 3.96 ± 0.84%, 112.58 ± 22.63%, and 124.69 ± 8.01% for dependent variables, respectively. The buccal film showed high swelling at pH 7 and swelling–deswelling behaviors in a water/ethanol environment. The surface pH, weight, and thickness were 8.11, 63.28 ± 6.18 mg, and 219.87 ± 44.28 µm, respectively. Nicotine content was found as 10.22 ± 0.46 mg/4 cm2. Maximum cumulative nicotine release was 9.82 ± 0.94 mg/4 cm2. Kinetic model fitted to the Korsmeyer-Peppas model and release exponent was 0.36, representing that release mechanism was controlled by Fickian diffusion release.
... These are of two types natural and synthetic Elastomer materials applied in chewing gum formulations. 16 Emulsifier it allows two immiscible phases to disperse and improve softness and ability to make bubble gum requires chewing consistency and mouth feel. It contributes to uptaking of saliva and softness during shelf life and hydration effect while chewing. ...
... NRT dapat membantu menghentikan kebiasaan merokok. [28] Klotrimazol dapat dihidrolisis dalam media asam serta tidak memiliki sifat fotosensitif tetapi sedikit higroskopis. Klotrimazol merupakan zat berwarna putih hingga kuning pucat, berbentuk kristal, bersifat basa lemah. ...
Article
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Tablet hisap banyak dikembangkan dalam industri farmasi karena kelebihannya yang lebih mudah diterima oleh pasien terutama pada anak-anak, rasa yang enak, bentuknya yang menarik seperti permen serta praktis dalam penggunaannya. Namun tidak semua zat aktif dapat dijadikan ke dalam bentuk sediaan ini sehingga studi-studi mengenai formulasi tablet hisap yang mengandung senyawa obat masih terbatas terutama zat aktif yang bersifat higroskopis. Kelembapan dapat mempengaruhi sifat fisika, kimia, dan mikrobiologi dari sediaan solid. Oleh karena itu dalam review artikel ini akan dibahas mengenai zat aktif higroskopis apa saja yang diformulasikan, standar pengujian evaluasi dalam menentukan kualitas sediaan tablet hisap, eksipien, polimer, serta metode pembuatan yang digunakan. Metode yang digunakan dalam artikel review ini yaitu studi pustaka dengan melakukan akses digital terhadap situs pencarian jurnal. Hasil menunjukkan zat aktif yang bersifat higroskopis dapat diformulasikan menjadi berbagai tipe tablet hisap yang memenuhi parameter yang telah ditetapkan dengan pemilihan metode, eksipien serta polimer yang tepat. Eksipien yang dapat digunakan antara lain adalah HPC, xanthan gum, talk, HPMC E-15, akasia, metil selulosa, kyron T114 dan PEG 6000.
... The gum yields blood nicotine levels, similar to those after smoking cigarettes (Russell et al., 1976). The choice of using nicotine gum instead of other methods of nicotine administration was related to its low cost, fast absorption (compared to transdermal patches), high bioavailability, easy consumption, availability in low doses (2-mg and 4-mg), and fewer side effects (Fagerström et al., 1993;Aslani and Rafiei, 2012). ...
Article
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Studies reported that tobacco addiction was related to visual impairments, but one unresolved issue is whether the impairments are related to the many compounds existing in the cigarettes or to the effects of nicotine. On the other hand, nicotine gum can be used as replacement therapy or as a neuroprotective agent for some diseases. The main purpose of this controlled trial is to investigate the effects of nicotine gum on vision. The ENIGMA-Vis trial aims to compare two dosages of nicotine gum (2 and 4 mg) and a placebo gum in a randomized, double-blind, placebo-controlled trial of 100 participants to be allocated into a single group assignment of repeated measures (two studies; N = 50 for each one). Eligibility criteria are healthy non-smokers not diagnosed with substance abuse and without an acute or chronic medical condition. Intervention will last three sessions for each participant with a window frame of 1 week per session. Study outcomes are (1) short-term effects of nicotine gum on contrast sensitivity; (2) short-term effects of nicotine gum on chromatic contrast discrimination; and (3) whether demographics, body mass index, or serum cotinine predicts response of visual processing. This study addresses an important gap in the effects of nicotine on vision. One of the main takeaways of this study is to understand the effects of nicotine on contrast sensitivity and chromatic contrast discrimination. This information will provide a further understanding of how nicotine interacts with early visual processes and help determine how the different components present during smoking can affect vision. Clinical Trial Registration Number: RBR-46tjy3.
... The unpleasant flavor of nicotine gums is, however, a key encounter concerning the patients' acceptance and amenability with suggested dose up regimens [34]. Thus, a study was carried out to formulate the gums using nicotine hydrogen tartrate due to its quick-release rate [35]. Nijhawan developed a stick of gum containing therapeutic benefits of nonsteroid anti-inflammatory drugs, H2 antagonist (ranitidine, cimetidine, famotidine), and/or a proton pump inhibitor (such as lansoprazole, pantoprazole, omeprazole, esomeprazole or rabeprazole). ...
Article
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The reason that the oral route attained such acceptance may be ascribed to its affluence of administration. Over the years, patient convenience- oriented exploration in the area of drug delivery has introduced potential innovative medicine delivery systems. The elegant drug delivery system is an amalgamation of science and dexterity with therapeutic prospect and presentability. It involves the administration of medications in a groundbreaking fashion with the assistance of cosmetics, wearable devices and oral drug delivery system which can also be used for ornamental purposes. Out of which, therapeutic chewing gum offers a highly suitable and amenable technique of dosing medications comprising children and elderlies. It is a potentially convenient means of administering medications either locally or systematically via the oral cavity. It bids innumerable gains over conventional drug delivery methods. Moreover, medicinal chewing gums involve the dynamic and constant masticatory actions for drug release. Currently, enriched expertise has made it promising to advance and fabricate medicated chewing gum with predefined properties and it could be a marketable triumph in the future. Apprehending this, several investigators and pharmaceutical companies are now engaged in developing innovative practices vis-à-vis medicated chewing gums by filing several patents in this area. The present manuscript also delivers a gestalt of various patented technology platforms based on different methods/ mechanisms employed for the preparation of medicated chewing gums.
... It can be used as smoking cessation aid and was confirmed by Food and Drug Administration (FDA) in 1984. Aslani and Rafiei [52] showed that the addition of 2 and 4 mg nicotine and aspartame as a sweetener and cherry and eucalyptus as flavoring agents had optimal chewing hardness and highest acceptability among smokers. The release of nicotine from 2 to 4 mg chewing gums at 45 min was reported 92% and 93%, respectively. ...
... It can be used as smoking cessation aid and was confirmed by Food and Drug Administration (FDA) in 1984. Aslani and Rafiei [52] showed that the addition of 2 and 4 mg nicotine and aspartame as a sweetener and cherry and eucalyptus as flavoring agents had optimal chewing hardness and highest acceptability among smokers. The release of nicotine from 2 to 4 mg chewing gums at 45 min was reported 92% and 93%, respectively. ...
Book
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The drug's bitter taste and poor palatability make oral drug administration a daunting task. But, taste-masked medicated chewing gum provides an elegant and palatable way of administrating drugs and nutritional supplements to children and older people. Medicated chewing gum (MCG) is a mix of natural or artificial resins with the active component, plasticizer, softeners, and sweetening or flavoring agents. The released drug can be absorbed via buccal mucosa or may reach the stomach for systemic effect. Medicated chewing gum has been exploited for various applications like dental caries, smoking cessation, analgesic, anti-emetic, obesity, diabetes, fungal infection, pain killer, etc. The medicated chewing gum can be formulated by three methods: the conventional melting method, the cooling-grinding method, and the direct compression method. The active ingredient release can be made sustained or modified using various techniques such as cyclodextrin- complexation, microencapsulation, ion exchange resin, buffering agents, etc. Chewing gums, being a palatable formulation, relies on effective taste-masking techniques such as the encapsulation method and a combination of flavor and sweetener. This manuscript provides a gestalt of recent patents and novel applications related to MCGs. Product quality tests for MCG are described by the European pharmacopeia, including content uniformity, weight variation, in vitro drug release, in vivo salivary and urinary studies, and ex vivo buccal permeation studies, etc. The chewing packaging utilizes aluminum, plastic, blister, cardboard material to provide elegance and protection. The manuscript also underlines MCG's regulatory aspects in various countries like USA, Europe, Australia, etc. Treatment of fungal diseases, probiotics, psycho spirituality, anesthetics, birth control gum, dental problems, smoking termination, long-lasting flavored, filled gums, timed-release, biodegradable chewing gums are some of the chic products to be seen in the future. With enhanced techniques and skills, researchers can make it possible to manufacture MCG with predefined properties. The book provides a platform to the new researchers owing to develop & formulate medicated chewing gums with pre-defined properties. Also, chewing gum applications have not been fully explored due to its therapeutic uncertainty and lack of high-quality standards. There is a need to design proper formulation, drug release mechanism & evaluation methods to make MCG meet new quality standards.
Article
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Мета роботи. Аналіз і систематизація даних літератури щодо призначення і класифікації гумок жувальних лікувальних, їх технології, методів дослідження і показників якості.Матеріали і методи. У роботі використано методи інформаційного пошуку, аналізу даних літератури щодо лікарської форми – гумка жувальна лікувальна.Результати й обговорення. Гумка жувальна лікувальна є зручною системою доставки лікарського засобу і може забезпечувати високу комплаєнтність пацієнта. Для виготовлення гумки жувальної лікувальної використовують метод плавлення; метод замороження, подрібнення і таблетування; метод прямого пресування. Фармакопейними показниками якості гумок є опис, ідентифікація, середня маса, однорідність маси, однорідність вмісту, розчинення, мікробіологічна чистота, кількісне визначення. У процесі розробки складу і технології гумок набір фармако-технологічних показників і методик випробувань суттєво відрізняється від фармакопейних і включає визначення численних органолептичних властивостей, вивчення текстури інструментальними методами.Висновок. Гумка жувальна лікувальна – це мобільна система доставки ліків, яка містить один або кілька активних інгредієнтів, що вивільняються шляхом жування. Розглянуто методи та особливості технології, фармако-технологічні показники і показники якості гумок жувальних лікувальних. Дана лікарська форма має переваги порівняно з традиційними системами доставки ліків, характеризується високим комплаєнсом. Серед трьох відомих методів отримання гумок, за рахунок появи готових основ промислового виробництва, все більшого застосування набуває метод прямого пресування.
Article
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The potential of chewing gum as a drug delivery system together with different formulation principles and methods of assessment are discussed in this article. The release of a drug from chewing gum is dependent upon its water solubility. Water soluble substances are released rapidly and completely from chewing gum and methods are available which retard their release from chewing gum to provide an extended release profile. Slightly water-soluble drugs are released slowly and incompletely from chewing gum and require special formulation techniques to produce a satisfactory release profile. Studies evaluating the potential application of medicated and non-medicated chewing gum in the treatment of local diseases in the oral cavity are described. Specific examples of the use of chewing gum as a delivery system for dental health, smoking cessation and antifungal therapy are cited. Few drugs are suitable candidates for incorporation into chewing gum formulations for the intention of their systemic delivery. Know-how derived from the development and manufacture of already existing medicated and non-medicated chewing gum, supplemented with today's knowledge of the principles of pharmaceutical formulation, constitute the basis for the development of the medicinal chewing gum of tomorrow. Key words: Buccal delivery, Increased release, Sustained release, Dental health, Oral candidiasis, Smoking cessation.
Article
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Release of nicotine from conventional gums and from gums made using a directly compressible gum base was studied using the European Pharmacopoeia apparatus for testing of medicated chewing gums. It was found that gum base and the method of preparation used in a formulation were important factors when controlling the release of drugs from chewing gum.
Article
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Even with effective smoking cessation medications, many smokers are unable to abruptly stop using tobacco. This finding has increased interest in smoking reduction as an interim step towards complete cessation. This multi-center, double-blind placebo-controlled study evaluated the efficacy and safety of nicotine 4 mg gum or nicotine 10 mg inhaler in helping smokers (N = 314) to reduce or quit smoking. It included smokers willing to control their smoking, and participants could set individual goals, to reduce or quit. The study was placebo-controlled, randomized in a ratio of 2:1 (Active:Placebo), and subjects could choose inhaler or gum after randomization. Outcome was short-term (from Week 6 to Month 4) and long-term (from Month 6 to Month 12) abstinence or reduction. Abstinence was defined as not a single cigarette smoked and expired CO readings of <10 ppm. Smoking reduction was defined as a reduction in number of cigarettes per day by 50% or more versus baseline, verified by a lower-than-baseline CO reading at each visit during the same periods. Significantly more smokers managed to quit in the Active group than in the Placebo group. Sustained abstinence rates at 4 months were 42/209 (20.1%) subjects in the Active group and 9/105 (8.6%) subjects in the Placebo group (p = 0.009). Sustained abstinence rates at 12 months were 39/209 (18.7%) and 9/105 (8.6%), respectively (p = 0.019). Smoking reduction did not differ between the groups, either at short-term or long-term. Twelve-month reduction results were 17.2% vs. 18.1%, respectively. No serious adverse events were reported. In conclusion, treatment with 10 mg nicotine inhaler or 4 mg nicotine chewing gum resulted in a significantly higher abstinence rate than placebo. In addition a large number of smokers managed to reduce their cigarette consumption by more than 50% compared to baseline.
Article
In recent years scientific and technological advancements have been made in the research and development of oral drug delivery system. The reasons that the oral route achieved such popularity may be in part attributed to its ease of administration. Chewing gum is one of the very popular oral confectionery products. Chewing gum is a combination of a water-insoluble phase, known as gum base (insoluble gum base resin), elastomers, emulsifiers, fillers, waxes, antioxidants, softeners, sweeteners, food colourings, flavoring agents, and in case of medical chewing gum, active substances. It offers various advantages over conventional drug delivery system. The manufacturing process of chewing gum takes from 5-15 min, but longer mixing time may be depending on the texture and function of gum base used. An In-vitro apparatus was specially designed and constructed for release testing of medicated chewing gums. The absorption of active substances through the buccal mucosa can be examined by both In-vitro and In-vivo methods. It was concluded that Chewing gum is an excellent drug delivery system for self-medication as it is convenient and can be administered discreetly without water.
Article
Zinc salts are added as a nutritional or functional ingredient in food and oral care products. The 1st experiment in this study investigated the taste and somatosensory effect of zinc salts (chloride, iodide, sulfate, bromide, acetate). The zinc salts had very little taste (bitter, salty, savory, sour, sweet), and the taste that was present was easily washed away with water rinses. The major oral quality of zinc was astringency, and the astringency lingered beyond expectoration. The 2nd experiment combined zinc salts with prototypical stimuli eliciting basic tastes. Zinc was a potent inhibitor of sweetness and bitterness (>70% reduction in taste) but did not affect salt, savory, or sour taste.
Article
Combating bitter taste in food, pharmaceuticals, and beverages remains a huge challenge. In the past, bitterness reduction was focused on pharmaceuticals and drugs; however, more recently, the most intense research is performed on the reduction of bitter or astringent taste in functional food or beverage applications. These foods and beverages possess inherent off-tastes due to fortification with healthy but poor-tasting actives. During the last 10years, tremendous progress in the elucidation of bitter taste reception and transduction on the cellular level was made and many new molecules and compounds to reduce bitter off-tastes were reported. The following review will be focused on the advances, in the area of bitter-masking molecules, during the last 10years. It will not cover other debittering strategies such as process optimization or biotransformations to reduce the amount of bitter ingredients, encapsulation, and other physical formulation technologies. The review will close with a short comparative study of various bitter maskers and some suggestions for flavor development of poor-tasting ingredients.