Menthol Flavors Research Articles

Formulation and Evaluation of Orodispersible Tablet of Domperidone

The aim of the present study was to develop and evaluate orodispersible tablets of domperidone by direct compression method. Sodium starch glycolate ( SCG ), Kollidone CLSF and sodium bicarbonate were used as disintegrants to achieve the desired disintegration time required for orodispersible tablets. To mask the bitter taste of drug, impart sweetness and to offer a better feeling in mouth, saccharin sodium, aspartame, citric acid, menthol and lemon flavor were also added. Mannitol and lactose were used as sugar based multifunctional diluents. The prepared tablets were evaluated for their physical (hardness, friability, weight variation), organoleptic (taste, mouth-feel, color) and functional (disintegration time) properties and for the drug content. The excipients were used in various concentrations in order to optimize the desired properties. SCG and Kollidone CLSF, used in 5.5% and 4% respectively, gave satisfactory disintegration time using BP instrument and within the mouth. Combination of saccharin sodium (1.5%) and aspartame (3%) along with mannitol (40%) and other excipients effectively masked the bitterness and provided satisfactory sweetness level. Incorporation of 0.05% menthol provided excellent mouth feeling as assessed by a panel of volunteers. Hardness and friability values were also optimized in the formulations to produce tablets of acceptable physical stability and mechanical strength. Weight variation and drug content of all formulations fully complied with the official specifications. DOI: http://dx.doi.org/10.3329/dujps.v10i2.11791 Dhaka Univ. J. Pharm. Sci. 10(2): 117-122, 2011 (December)

Introduction: Mentholated cigarettes and public health

The Food and Drug Administration’s Center for Tobacco Products (CTP) oversees the implementation of the Family Smoking Prevention and Tobacco Control Act, H.R. 1256. Among its many provisions, section 907(a) of the Tobacco Control Act banned the use of characterizing flavors, specifically excluding only tobacco and menthol flavors from the ban. According to section 907(e)(2), “[n]ot later than 1 year after its establishment, the Tobacco Product Scientific Advisory Committee shall submit to the Secretary the report and recommendations required pursuant to [menthol],” which, according to section 907(e)(1), is “the issue of the impact of the use of menthol in cigarettes on the public health, including such use among children, African-Americans, Hispanics, and other racial and ethnic minorities.” The inaugural meeting of the Food and Drug Administration’s Tobacco Products Scientific Advisory Committee (TPSAC) was held March 30–31, 2010 in Washington, DC. In preparation for this meeting, CTP reviewed peer-reviewed literature on menthol and tobacco as indentified by the National Cancer Institute’s “Bibliography of literature on menthol and tobacco”, and seven scientific presentations were made, including the use of menthol cigarettes (epidemiology), smoking topography and sensations associated with menthol cigarettes, marketing of menthol cigarettes, menthol cigarettes and initiation of smoking behavior, menthol cigarettes and nicotine dependence, menthol cigarettes and cessation of tobacco use, and the health effects of menthol cigarettes as compared to non-menthol cigarettes. Following this initial presentation, additional information was collected through FDA investigation, as well as recommendations from the public, research community and tobacco industry, resulting in comprehensive reviews. Thus, this supplement brings together the extant peer-reviewed information on these seven topics.

The menthol smoker: Tobacco industry research on consumer sensory perception of menthol cigarettes and its role in smoking behavior

The use of menthol in cigarettes is actively promoted by the tobacco industry for its perceived sensory benefits, and smokers of menthol cigarettes commonly differ from nonmenthol smokers in markers of smoking behavior and addiction. In this study, we analyzed internal tobacco industry documents to describe the relationships between sensory perception and the attitudes, preferences, and patterns of cigarette use among menthol smokers. Two unique types of menthol smoker emerged from this analysis: those who cannot tolerate the harshness and irritation associated with smoking nonmenthol cigarettes, and those who seek out the specific menthol flavor and associated physical sensation. Among the first segment of menthol smokers, menthol reduces negative sensory characteristics associated with smoking. This segment of smokers may include a large proportion of occasional smokers or young people, as well as smokers who have "traded down" to a less strong cigarette because of perceived harshness or negative health effects. Some established menthol smokers, on the other hand, appear to be tolerant of and even actively seek stronger sensory attributes, including higher menthol levels. Smokers of these "stronger" menthols have traditionally been disproportionately Black and male. Some beginning or occasional smokers may adopt menthols for their mild properties and to cover up the taste of tobacco, but then develop a stronger desire for the menthol taste over time. Future research measuring smoking behavior and evaluating cessation outcomes of menthol smokers should consider the duration of menthol use and differentiate smokers according to their reasons for using menthols.

Monoterpene metabolism. Cloning, expression, and characterization of menthone reductases from peppermint.

(-)-Menthone is the predominant monoterpene produced in the essential oil of maturing peppermint (Mentha x piperita) leaves during the filling of epidermal oil glands. This early biosynthetic process is followed by a second, later oil maturation program (approximately coincident with flower initiation) in which the C3-carbonyl of menthone is reduced to yield (-)-(3R)-menthol and (+)-(3S)-neomenthol by two distinct NADPH-dependent ketoreductases. An activity-based in situ screen, by expression in Escherichia coli of 23 putative redox enzymes from an immature peppermint oil gland expressed sequence tag library, was used to isolate a cDNA encoding the latter menthone:(+)-(3S)-neomenthol reductase. Reverse transcription-PCR amplification and RACE were used to acquire the former menthone:(-)-(3R)-menthol reductase directly from mRNA isolated from the oil gland secretory cells of mature leaves. The deduced amino acid sequences of these two reductases share 73% identity, provide no apparent subcellular targeting information, and predict inclusion in the short-chain dehydrogenase/reductase family of enzymes. The menthone:(+)-(3S)-neomenthol reductase cDNA encodes a 35,722-D protein, and the recombinant enzyme yields 94% (+)-(3S)-neomenthol and 6% (-)-(3R)-menthol from (-)-menthone as substrate, and 86% (+)-(3S)-isomenthol and 14% (+)-(3R)-neoisomenthol from (+)-isomenthone as substrate, has a pH optimum of 9.3, and K(m) values of 674 mum, > 1 mm, and 10 mum for menthone, isomenthone, and NADPH, respectively, with a k(cat) of 0.06 s(-1). The recombinant menthone:(-)-(3R)-menthol reductase has a deduced size of 34,070 D and converts (-)-menthone to 95% (-)-(3R)-menthol and 5% (+)-(3S)-neomenthol, and (+)-isomenthone to 87% (+)-(3R)-neoisomenthol and 13% (+)-(3S)-isomenthol, displays optimum activity at neutral pH, and has K(m) values of 3.0 mum, 41 mum, and 0.12 mum for menthone, isomenthone, and NADPH, respectively, with a k(cat) of 0.6 s(-1). The respective activities of these menthone reductases account for all of the menthol isomers found in the essential oil of peppermint. Biotechnological exploitation of these genes could lead to improved production yields of (-)-menthol, the principal and characteristic flavor component of peppermint.

Mentholated cigarettes and smoking habits in whites and blacks

Objective: To determine if cigarette mentholation is associated with the frequency of smoking and with quitting, and whether mentholation explains racial differences in these two smoking behaviours. Design: Cross sectional...

SHORT COMMUNICATION Determination of encapsulated menthol flavour using thermal desorption gas chromatography

The analysis of methol in encapsulated products is challenging due tothe nature of the encapsulating matrices and the volatility of the analyte. Normal sampling/extraction procedures cannot be applied to the different types of menthol encapsulated products, due to variable extraction efficiencies of the analyte. This paper details the extraction and analysis of menthol flavour using a two stage thermal desorption GC process. This two stage thermal desorption system, using a Tenax TR packed cold trap, enables a narrow band of the extracted menthol to be focused onto the GC column. The method showed linearity in the range of 0.2-0.8mg of menthol with a correlation coefficient greater than 0.999. Average instrumental precision of 3% RSD was determined and method precision was in the range of 2.1-9.4% RSD. This method was specific tomenthol showing no interfering peaks. All the menthol was extracted in one extraction step. The specific analysis of menthol in encapsulated products allowed comparison of the efficiency of encapsulating processes, by comparing menthol loading values. RSD values for the different microparticles also indicate the relative homogeneity of the systems.

Psychophysical characterization of new sweeteners of commercial importance for the EC food industry

Quantitative psychophysical information on the perceptual characteristics of sucrose (as reference), sodium cyclamate, aspartame, neohesperidin dihydrochalcone (NHDHC) and maltitol were established through the determination and the modelling of their concentration-response ( C-R) functions according to linear, Beidler or Hill equations, the recording of the time-intensity ( T-I) curves with the determination of the T-I parameters for each sweetener, and the establishment of the sensory profile of the sweetener solutions by the QDA technique. Bulk and intense sweeteners present dissimilar C-R functions. The C-R function observed for maltitol is linear while aspartame, cyclamate and NHDHC exhibit a saturation plateau around 10–13% sucrose equivalent. Temporal characteristics of aspartame and cyclamate are comparable to those of sucrose and maltitol, whereas the T-I characteristics of NHDHC contrast with those of the other sweeteners, essentially because of its long onset and persistence times. Bitter taste and bitter aftertaste are attributes that differentiate maltitol and sucrose from artificial sweeteners. Bitter and metallic are non-sweet aftertastes characteristic of cyclamate, while NHDHC is mainly defined by a liquorice-like and cooling/ menthol flavour. Caramel flavour is associated with nutritive sweeteners, and burnt sugar flavour is related to synthetic sweeteners, except cyclamate, which is characterized by both flavours.

The use of flavor in cigarette substitutes

Cigarette smokers identify flavor as an important factor in the pleasure derived from smoking and for their choice of cigarette brand. The issue of cigarette flavor has received a great deal of study by cigarette manufacturers but relatively little by academic investigators. The paucity of literature is particularly acute in terms of the importance of flavor in cigarette substitutes, which are used to help people to reduce or quit smoking. In the current study, five different types of flavors added to a plastic cigarette substitute were assessed in experienced smokers. There were two menthol-like flavors and three tobacco-like flavors. Two groups of smokers were tested: menthol smokers and “regular” (non-menthol) smokers. Both types of smokers liked the two menthol flavors significantly more than placebo and rated the menthol flavors and the cigarette flavor as significantly more satisfying than placebo. Craving was differentially reduced in the two groups of smokers. Menthol smokers showed a small reduction in craving with the placebo, with a significant enhancement of this reduction seen with the addition of the “EZ Quit” menthol flavor.

Comparative genotoxicity testing of mainstream whole smoke from cigarettes which burn or heat tobacco

The genotoxic potential of mainstream whole smoke (MWS) from cigarettes which heat tobacco (TEST) was compared to the genotoxic potential of MWS from a cigarette which burns tobacco (REFERENCE). MWS was collected from a University of Kentucky 1R4F cigarette (REFERENCE) and two TEST cigarettes, one with regular flavor and the other with menthol flavor. All cigarettes were smoked on a smoking machine and the particulate phase was collected on Cambridge filter pads. The vapor phase, which passed through the pad, was bubbled into a dimethyl sulfoxide (DMSO) trap. The filter pad was extracted with the DMSO in the trap and additional DMSO to obtain MWS. MWS representing an identical number of cigarettes was tested to make a per-cigarette comparison of their genotoxic potential. REFERENCE MWS was mutagenic and cytotoxic in the Ames assay in the presence of metabolic activation while it was cytotoxic but not mutagenic in the absence of metabolic activation. Statistically significant increases in frequency of both sister-chromatid exchanges and chromosomal aberrations were observed in Chinese hamster ovary cells exposed to REFERENCE MWS with and without metabolic activation. MWS from the TEST cigarettes, with either regular or menthol flavor, was neither cytotoxic nor mutagenic in any of these assays. In summary, MWS from the 2 TEST cigarettes was neither genotoxic nor cytotoxic under conditions where MWS from the REFERENCE cigarettes was genotoxic and/or cytotoxic in a concentration-dependent manner.