European Journal of Scientific Research

ISSN 1450-216X Vol.46 No.2 (2010), pp.194-203

© EuroJournals Publishing, Inc. 2010
http://www.eurojournals.com/ejsr.htm

Evaluation and Standardization of Essential Oils for

Development of Alternative Dosage Forms

Anupam K Sachan
Dayanand Dinanath College, Institute of Pharmacy, Kanpur, India

Nikhil K Sachan
University Institute of Pharmacy, Chhatrapati Shahu Ji Maharaj University, Kanpur, India
E-mail: nikhilsachan@gmail.com
Tel: +91-9307755497; Fax: +91-512-2573231

Shailesh Kumar
Dayanand Dinanath College, Institute of Pharmacy, Kanpur, India

Ayushy Sachan
Dayanand Dinanath College, Institute of Pharmacy, Kanpur, India

Sudhir S. Gangwar
Department of Pharmacy, G.S.V.M. Govt. Medical College, Kanpur, India

Abstract

Conventional means for delivery of essential oils are elixirs or the soft gels. In
present study, the chewable tablets are proposed as means for their utility in delivery of
volatile therapeutic ingredients like essential oils as a better alternative of conventional
options. This study envisage the pharmaceutical characterization and evaluation of caraway
oil and peppermint oil through marker compounds using TLC, HPLC, HPTLC and gas
chromatography. The two oils are used internally for symptomatic treatment of irritable
bowel syndrome, and digestive disorders such as flatulence, gastritis antispasmodic,
carminative, analgesic and for cure of dyspepsia. The oils were loaded to granules
previously standardized through GC and HPTLC for their identity and quantification of
marker compound, and their compatibility testing with excipients was performed using
TLC and HPLC. Accelerated stability testing, for availability of marker compound in
formulated tablets, conducted by storing the tablets under different stress conditions.

Keywords: Volatile oils, drug delivery, chewable tablets, chromatographic

standardization

1. Introduction
Essential oils have been used by human being since long back for various therapeutic purposes
(Thompson, Coon, and Erenst, 2002) externally and internally, described in the pharmacopoeia,
traditional systems of medicine and reported in folk medicine. The selected oils ‘atheroleum menthae
piperitae’ (WHO) i.e. the peppermint oil and caraway oil are having proven therapeutic potential and
used internally for the treatment of non-ulcer dyspepsia, flatulence, gastritis also have antispasmodic,
Evaluation and Standardization of Essential Oils for Development of Alternative Dosage Forms 195

carminative, analgesic, flavouring properties (British Herbal Pharmacopoeia, 1979; Wren, 1985;
Wichtl, 1994; May, 1996). In India the two oils are used widely in different forms by common people
for the relief of dyspepsia, gastric spasm and carminative purpose in the form of aromatic waters, soft
gelatin capsules or as elixirs, moreover the people are taking several products as breath freshener. The
present concept to formulate these essential oils in the form of chewable dosage forms so that these can
be administered for such therapeutic uses and can provide simultaneously breath freshness to consumer
in view of the urban lifestyle. Chewable dosage forms, such as soft pill, tablets, gums, and, most
recently, “chewy squares,”have long been part of the pharmacist’s armamentarium (Liberman,
Lachman and Schwartz, 2005). Delivery of essential oils through chewable tablets offers better
palatability, by-passing first pass metabolism, better bioavailability through enhancing dissolution
steps, patience convenience for the no need of water for swallowing, rapid onset of action, improved
patient acceptance (especially in pediatrics) through pleasant, and product distinctiveness from a
marketing perspective, improved entrapment stability and comparative low production cost (Sachan,
2005). The people usually suffering with the gastric problems and used to take these oils very
frequently and the fresh feel that can be rendered by such chewable dosage forms will be an added
advantage. The present study proposed and examined a commercially feasible approach for
standardization and quantification of the peppermint oil and caraway oils for their further formulation
to chewable tablets as a better alternative of conventional options.
Aetheroleum Menthae Piperitae (peppermint oil) is the essential oil obtained by steam
distillation of the fresh overground parts of Mentha piperita L. (Labiatae), commercially cultivated in
India, eastern and northern Europe and the United States of America, and is found in Africa (FCC,
2001). The plant is vernacularly known as Amentha, american mint, balm mint, brandy mint, cabra-
caa, curled mint, dounmenta piperita, hierbabuena, hortela pimenta, Katzenkraut, lamb mint, lamenta,
lamint, mentapiemonte, mentea peperina, mentha pepe, menthe, menthe anglaise, menthepoivrée, moto
yuyo, nána, ni naa, ni’na el fulfully, pepermin, pepper mint, peppermint, Pfefferminze,
Pfefferminzblätter, piperita, pudeena, pum hub, yerba mota. It is a perennial herb, with 30–90cm hight,
stems square erect or ascending, branched, the upper portion always quadrangular and leaves opposite,
petiolate, ovate-oblong to oblong-lanceolate, serrate, pointed; dark green on the upper surface (Foster,
1996). The peppermint oil is a colourless or pale yellow or a pale greenish yellow liquid with its
characteristic penetrating odour and characteristic pungent taste followed by cooling sensation (Peirce,
1999). The major constituents are menthol (30–55%) and menthone (14–32%). Menthol occurs mostly
in the free alcohol form, with small quantities as the acetate (3–5%) and valerate esters. Other
monoterpenes present include isomenthone (2–10%), 1, 8-cineole (6–14%), a-pinene (1.0–1.5%), b-
pinene (1–2%), limonene (1–5%), neomenthol (2.5–3.5%) and menthofuran (1–9%). It is taken 0.2 to
0.4 ml three times a day for therapeutic use or may be taken in such doses when felt required by a
person for removal of mouth odour or as breath freshener (Adams, 1995; Scavroni et al., 2005).
Caraway oil is the essential oil obtained by steam distillation of the dried, ripe fruit of Carum
carvi, Linne (Family: Umbelliferae), found in Europe, Siberia, Caucasus, India, Mongolia and
Morocco etc. Caraway is normally a biennial much-branched herb, 30 - 80cm in height, with narrow
finely grooved leafy stems. It produces a deep taproot and a rosette of dark green, finely cut, feathery
leaves in the establishment year. It has a high vernalisation requirement to initiate the production of
flowering stems in the second year, which grow to a height of up to 75cm. The flowers are produced
on umbels, are white and 2-3 mm across, the outer ones larger than the inner ones. They open from late
April onwards and are succeeded by fruits which are 3-6 mm long, and light brown, ripening from
early July. Oil is a clear, colourless or pale yellow liquid, visibly free from water with characteristic
aromatic odour and a caraway taste. Caraway oil contains 50 to 60% of the ketone carvone and from 40
to 50% of the terpene d-limonene with small amounts of other constituents, including carveol and
dihydrocarvone (B.P. 1988). The average single dose of oil is 2 to 3 drops on sugar. The average daily
dose of oil is 3 to 6 drops essential oil for internal use (Schulz, Hänsel, Tyler, 1998; Grieve, 1982;
Castleman 1991).
196 Anupam K Sachan, Nikhil K Sachan, Shailesh Kumar,
Ayushy Sachan and Sudhir S. Gangwar

The oils were subjected to identification as per compendia method by TLC and quantification
by gas chromatography and by HPTLC identifying a marker compound and subjected to accelerated
stability testing one by one and in combination to demonstrate the physical and chemical stability of a
drug product at a variety of environment conditions including temperature, humidity & light (USP24/
NF18, 2000). Requirements for stability studies are defined in several international conferences on
harmonization guidelines and include storage conditions of 250C/60%RH, 300C/60%RH and 400C/75
% relatively. A drug-excipient compatibility analysis was performed by storing the pre-compressed
granules formulated for tablet preparation in glass vials at different storage conditions.

2. Materials and Methods

2.1. General
Materials: Peppermint oil (Arora Pharmaceuticals), Caraway oil (Siva Aromatics), Mannitol (Getec
Ltd), Dicalcium phosphate (Enar Chemie Ltd), Hydroxy propyl cellulose (Dow Chemicals), Syloid
(W.R. Grace), Cabosil (Cabot Sanmar Ltd), Stearic acid (Mallinckdrot), Magnesium stearate (S. Kant
Healthcare), Fl Novamint Peppermint 5060 40T (Firmenich), Fl Taste Mask Powder 501482 T P0424
(Firmenich), ProSolv SMCC50 (Penwest), NutraSweet Powder (NutraSweet), Carbopol 974 P NF
(Noveon). Instruments: Planetary mixer (M/s Dito Sama, France), Tablet friability test apparatus
(Arkey Labtromix, India), Monsanto tester (Aarkey Labtromix, India), Fluidized bed dryer (Retsch
Gmbh & Co, Germany), USP – Tapped density apparatus (Electrolab, India), Rotatory tablet
compression-machine (Rimek, India), Mechanical stirrer (Remi, India), Digimatic caliper (Mitutoyo,
Japan), Humidity chamber (Thermolab, India), 784KFP Titrino (Metrohm), HPTL Chromatography
(Camag, Switzerland), I.R. moisture balance (Guru Nanak Instrument, India), Clarus500 Gas
Chromatograph (Perkin Elmer).

2.2. Methods
Identification of the Marker Compound: Identification of the marker compound was carried out by
thin layer chromatography; the samples were applied in the form of bands on a precoated silica gel
GF254 aluminium plate (Camag, Switzerland). The solvent system of toluene and ethyl acetate (95:5)
was used for the development; compounds were detected by spraying anisaldehyde sulfuric acid
reagent after drying at 1050C for 5 minutes. The plate was visualized after spraying anisaldehyde
sulfuric acid reagent and Rf values for standard and samples were recorded and colour of band was
matched (Mukharjee, 2002; Harbone, 1998; Abourashed et al., 2004; Jones, 1998; Škrinjar, 2009).

Quantitative Estimation of the Marker Compound: High Performance Thin Layer

Chromatography: Quantitative estimation of the marker compound was carried out by HPTLC; the
samples were applied in the form of bands on a precoated silica gel GF254 aluminium plate (Camag,
LinomatIV, Switzerland). The solvent system of toluene and ethyl acetate (95:5) was used for the
development, compound were detected by spraying anisaldehyde solution after drying at 1050C for 5
minutes. The plate was visualized after spraying anisaldehyde sulfuric acid reagent. The scanning was
done at λmax-515 nm for carvone and λmax-610 nm for menthol, using Camag TLC scanner 3.
Regression analysis and statistical data were generated. Draw calibration curve of menthol and carvone
and then calculated the marker compound in the sample with reference to area by using wimCATS
Planar Chromatography Manager (Jones, 1998; Škrinjar, 2009; Mukharjee, 2002).
AREA (sample) X DILUTION (standard) POTENCY
FORMULA = ---------------------------------------------- X ------------------X100
AREA (standard) X DILUTION (sample) 100
Evaluation and Standardization of Essential Oils for Development of Alternative Dosage Forms 197

Gas Chromatography: A very dilute concentration of peppermint oil and caraway oil was run
in the column DB-1 (30mx250µm) with reference to standard menthol and carvone. The flow rate was
0.8ml/min; tenperature maintained 900C for 5 minute1500C for 5 minute and 2300C for 10 minute.
Injector and detector were used 2400 and 2800C respectively. The quantitative amount of marker
compound was calculated in the sample with reference to the area by using CLARUS-500Gas
Chromatograph (Mukharjee, 2002; Adams, 1995).

AREA (sample) X DILUTION (standard) POTENCY

FORMULA = ------------------------------------------- X ----------------X100
AREA (standard) X DILUTION (sample) 100

Drug Stability Studies: The drug (peppermint oil & caraway oil) was packed in sealed glass vials
individually and the admixture of both the drug at the ratio 1:1 were kept at different storage
conditions, 50C, 250C & 60%RH and 400C&75% relative humidity for one month and evaluated after
interval of one week (ICH Guidelines, 2003).

Drug- Excipients Compatibility Studies: Admixtures of the drug and excipients was mixed properly
in proportions of 1:5 respectively and packed in glass vials, then compatibility studies3 was done by
storing at different storage conditions50C, 250C & 60%RH and 400C&75% relative humidity for one
month and evaluated after interval of one week (Bhattacharya et al., 2006; IPEC, 2008; Liberman,
Lachman and Schwartz, 2005).

3. Results and Discussion

3.1. Identification of the Marker Compound
The menthol and carvone were taken as suitable markers for the estimation of peppermint and caraway
oils respectively, and were identified for their presence in the essential oils samples by high
performance thin layer chromatography by taking the standard marker compound loaded side by side
in the TLC and comparing colour and retention factor after development of plate (Jones, 1998;
Škrinjar, 2009; Mukharjee, 2002). Results of HPTLC chromatograms (Fig. 1) of samples depicted the
same Rf value and colour of the peak for essential oil samples by high performance thin layer
chromatography as of the, selected marker compounds for quantification of the essential oils (Table 1).

Figure 1: HPTLC plate chromatogram of oils and standard marker compounds

198 Anupam K Sachan, Nikhil K Sachan, Shailesh Kumar,
Ayushy Sachan and Sudhir S. Gangwar

Table 1: Identification of the marker compound

Description Standard Peppermint Standard Caraway oil

(Menthol) oil (Carvone)
Rf values 0.22 0.23 0.52 0.52
Colour Blue Blue Raspberry Red Raspberry Red

3.2. Physical Standards

Essential oils were subjected to tests for physical parameters for compliance or otherwise not with the
pharmacopoeial standards. The results tabulated below (Table 2) for two oils showed them to be
compliant with the standard limits, which supports the identity of sample and give an indication about
their quality (Singhal, Kulkarni, Rege, 2001; B.P. 1988, Jones, 1998).

Table 2: Physical standards of the peppermint oil and caraway oil

Sample. Colour Odour Acid Relative Refractive Optical Miscibility

Value Density Index Rotation
Peppermint Greenish Characteristic 0.83 0.912 1.451 -21±3 Miscible with ethanol (96%),
oil yellow ether & methylene chloride
Caraway oil Pale Characteristic 0.41 0.904 1.484 +78±2 Miscible in 2-10 volume of
yellow 80% ethanol, with
opalescence; clearly soluble
in equal volume of 90%
alcohol.

3.3. Quantitative Estimation of Marker Compound

Quantitative estimation of the marker compound, carried out by HPTLC (Fig. 2) and GC (Fig. 3), the
GC seems to be a better accurate method than HPTLC for the estimation of essential oil (Adams,
1995). The percentage of marker compound estimated by both HPTLC and GC is shown in table 3.
The methods are sufficiently reproducible and validated to be used for estimation of these oils. The GC
and HPLC both are widely accepted techniques in the pharmaceutical industry thus it presents a scope
for these oils in herbal and polyherbal formulations (Mukharjee, 2002; Harbone, 1998; Abourashed et
al., 2004; Jones, 1998; Škrinjar, 2009).

Figure 2.1: HPTLC chromatograms all tracks of standards (menthol) and sample at 610 nm
Evaluation and Standardization of Essential Oils for Development of Alternative Dosage Forms 199
Figure 2.2: HPTLC chromatograms all tracks of standards (carvone) and sample at 515 nm

Figure 3.1: Gas Chromatogram of CARVONE (Standard)

Table 3: Quantitative estimation of marker compound

S.N. Techniques Menthol (%w/w) Carvone (%w/w)

1. HPTLChromatography 58.64 58.53
2. Gas Chromatography 57.80 62.66
200 Anupam K Sachan, Nikhil K Sachan, Shailesh Kumar,
Ayushy Sachan and Sudhir S. Gangwar

Figure 3.2: Gas Chromatogram of menthol (Standard)

Figure 3.3: Gas Chromatogram of caraway oil (Sample)

Figure 3.4: Gas Chromatogram of peppermint oil (Sample)

3.3. Drug Stability Studies

A thorough knowledge of the chemical and physical stability of drugs and dosage forms is critical in
the development and evaluation of pharmaceuticals (Yoshioka and Stella, 2002). Chemical degradation
and physical degradation of drug substances may change their pharmacological effects, resulting in
altered efficacy therapeutic as well as toxicological consequences. Because pharmaceuticals are used
Evaluation and Standardization of Essential Oils for Development of Alternative Dosage Forms 201

therapeutically based on their efficacy and safety, they should be stable and maintain their quality until
the time of usage or until their expiration date (Yoshioka and Stella, 2002). The quality should be
maintained under the various conditions that pharmaceuticals encounter, during production, storage in
warehouses, transportation, and storage in hospital and community pharmacies, as well as in the home.
Therefore, understanding the factors that alter the stability of these essential oils and identifying ways
to guarantee their stability are critical before formulating any dosage form (USP, 2006). The Drug
Stability studies conducted for the peppermint and caraway oils showed that there was no physical
change observed in any sample of peppermint oil or caraway oil or their mixture in 1:1 ratio stored
under 50C, 250C with 60%RH, and 400C with 75%RH stored in glass vial packaging moreover there
was no any new peak or alteration of retention time observed for these samples when compared with
zero time observations under similar conditions. Thus the two oils are sufficiently stable suitable for
the formulation of chewable tablets and there is no any degradation observed on accelerated stability
test condition for a month time period.

3.4. Drug- excipients Compatibility Studies

Almost all pharmaceutical dosage forms include excipients (Sharma and Joshi, 2007). Indeed, in most
dosage forms the amounts of one or more excipients are greater than the amounts of the active
pharmaceutical ingredients (APIs) present in them (Sachan and Singh, 2006). Excipients interact with
the API in the final formulated dosage form and/or provide a matrix that affects the critical quality
attributes of the active pharmaceutical ingredients, including stability and bioavailability (Crowley and
Martini 2001). Excipients also influence the safety and effectiveness of drugs depending on the route
of administration, so qualitative and quantitative understanding of the excipient’s composition is
critically important to the understanding of a dosage form’s bioavailability and bio-equivalence (USP
2006; Sonal, S. Et al., 2008)

Table 4: Drug-excipient Compatibility Studies

Storage time: Four weeks Packing: Glass vials

Stress 5 0C 250C with 400C with

Conditions 60%RH 75%RH
Composition
of granules
Lactose, Sucrose, Mannitol, CMC Sodium, Mg stearate, No physical changes No physical changes No physical changes
Light Mg carbonate, Di calcium Phosphate, Talc, in samples and no in samples and no in samples and no
Aerosil, Syloid, Starch, Microcrystalline Cellulose, Ethyl new peak observed new peak observed new peak observed
Cellulose, Hydroxypropyl- methyl cellulose, Stearic acid, in GC. in GC. in GC.
Aspartame, ProSolv SMCC, Carbopol974P NF

The quality of medicines depends not only on the active principles and manufacturing process
but this also depend upon performance of excipients (Sachan and Bhattacharya, 2006). The magnitude
of this effect will depend on the characteristics of the drug and on the quantity and properties of the
excipients. Chemical and physical stability of active ingredients in fixed dosage forms may become
very complicated due to the presence of two or more active ingredients, or because potentially more or
unique excipients are required to achieve the desired release rate for both actives (Roger, et al., 2009).
Not only active ingredients may react each other to form degradants which may not seen in single
dosage form, but also active ingredients may react with excipients which are otherwise compatible
with one of single active ingredients (Jin, Madieh, Augsburger, 2007). These attributes create many
new challenges for formulation development and pharmaceutical analysis of fixed combination
products. Strategic design in drug-drug and drug-excipient compatibility studies and development of
appropriate analytical method which is able to detect all potential impurities, and degradants, are very
important in successfully developing a stable fixed combination dosage form (Klick, S. Et al., 2005).
202 Anupam K Sachan, Nikhil K Sachan, Shailesh Kumar,
Ayushy Sachan and Sudhir S. Gangwar

The Drug- Excipient compatibility studies showed that there is no change at accelerated storage
condition for a month time period.

4. Summary and Concluding Remarks

In conclusion, the peppermint oil and caraway oil were confirmed for their identity and could be
standardized for various parameters including the quantification by both HPTLC and gas
chromatography. The method so developed is useful for routine analysis of these oils and can be
further adopted fot the assay of proposed chewable tablet dosage forms which seems to be promising
alternative of conventional means of therapeutic delivery of essential oils with added advantages of
mouth and breathe falouring, convenience of administration and low cost production. Drug excipients
compatibility study has shown no chemical interaction with volatile oil and excipients used. The
further research is ongoing towards the formulation, optimization, scale up, packaging and real time
stability testing for the chewable tablet formulations with these essential oils.

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