Drug and Excipients Profile

2. Drug and excipients profile

2.1 Mesembrine
Mesembrine is a bicyclic molecule and has two bridgehead chiral carbons between the five-
membered ring and the six-membered ring (highlighted in green in the figure below).
Because of its structure and bioactivity, mesembrine has been a target for total synthesis over
the past 40 years. Over 40 total syntheses have been reported for mesembrine, most of which
focused on different approaches and strategies for the construction of the bicyclic ring system
and the quaternary carbon 26.
MeO
MeO

N O
Me H
Figure 2: Structure of mesembrine

2.1.1 Description
 Chemical name: 3a-(3,4-dimethoxyphenyl)-1-methyloctahydro-6H-indol-6-one.
 Molecular formula: C17H23NO3
 Density: 1.1±0.1 g/cm3
 Vapour pressure: 0.0±1.0 mmHg at 25°C
 Surface tension: 41.6±3.0
 Molar volume: 255.2±3.0 cm3
 Molar refractivity: 81.1±0.3 cm3
 Boiling point: 419.2±45.0 °C
 Pka: 8.335
 LogP: 2.22
 Melting point: 205-206 °C
 Solubility: Free base, freely soluble in alcohol, chloroform, acetone, slightly soluble
in ether, practically insoluble in benzene, petroleum ether, alkalies 27.

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2.1.2 Pharmacology
Mesembrine was studied to be serotonin uptake inhibitor as well as used for the treatment
of central nervous system disorder. Mesembrine is also used as phosphodiesterase-4
inhibitor (PDE4) and used in management of asthma, chronic pulmonary diseases and
depression 28.

2.1.3 Mechanism of action

The mechanisms of action on the central nervous system (CNS) of a standardized extract
of S. tortuosum (Mesembrin) were recently identified as comprising blockade of the
serotonin (5-HT) transporter and selective inhibition of the phosphodiesterase-4 (PDE4)
enzyme 29. 5-HT reuptake inhibitors (SSRIs) are widely used for the treatment of anxiety
disorders and depression 30. However, a combination of SSRIs with a PDE4 inhibitor has
been argued to have synergistic therapeutic potential in CNS disorders by providing greater
symptomatic efficacy and broader therapeutic utility than either as a drug on its own. In
particular, repeated treatment with SSRIs can upregulate PDE4 31, which in turn reduces
the sensitivity to SSRIs in response to long-term treatment, suggesting that dual treatment
with SSRIs and PDE4 inhibitors may be a promising approach 32.

2.1.4 Uses
Tablets and capsules of mesembrine is being used successfully by a number of psychiatrists,
psychologists and doctors with excellent results for anxiety states and mild to moderate
depression; and they can also be used by the lay public as supplements to elevate mood and
for stress and tension. In addition, Mesembrine common use for the stress and mental
fatigue of modern industrial living, Mesembrine has been used as a natural supplement in:
 uplifts the mood
 decrease anxiety, stress and tension
 gives energy
Mesembrine elevates mood and decreases anxiety, stress and tension.

2.1.5 Side effects

Very few people experience side-effects. The reported side-effects include occasional
episodes of:

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 Drug and Excipients Profile

 Mild headache
 Slight nausea, no vomiting
 Soft stool or loose stool with no cramping
 Transient increase in anxiety or irritability an hour after initiating
treatment, which resolves after an hour or so
 Insomnia: corrected by lowering the dose or taking the product not later than midday
 A feeling of sedation: corrected by taking the product as a single 50mg dose at night
33.

2.1.6 Tradition & modern use

Kanna or Channa meaning “chew(able) thing” is an absolutely miraculous plant. It has been
recognized for its mood-enhancing capabilities for hundreds of years. This plant is most
commonly used in South Africa since prehistoric times. There are many different methods
of consuming the plant; it can be chewed, made into tea or tincture, smoked or snuffed. The
medicinal qualities often last for many hours or even days after the ingestion of Kanna,
lightening one’s mood and offering a mild euphoria that isn’t necessarily a “high” but a
feeling of “I feel great!”33.

2.2 Hypromellose
2.2.1 Nonproprietary Names
BP: Hypromellose
JP: Hydroxypropylmethylcellulose
PhEur: Hypromellosum
USP: Hypromellose

2.2.2 Synonyms
Benecel MHPC; E464; hydroxypropyl methylcellulose; HPMC; Methocel; methylcellulose
propylene glycol ether; methyl hydroxypropylcellulose; Metolose; Tylopur.

2.2.3 Empirical Formula and Molecular Weight

The PhEur 2005 describes hypromellose as a partly Omethylated and O-(2-
hydroxypropylated) cellulose. It is available in several grades that vary in viscosity and extent
of substitution. Grades may be distinguished by appending a number indicative of the

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apparent viscosity, in mPa s, of a 2% w/w aqueous solution at 20°C. Hypromellose defined in

the USP 28 specifies the substitution type by appending a four-digit number to the
nonproprietary name: e.g., hypromellose 1828. The first two digits refer to the approximate
percentage content of the methoxy group (OCH 3). The second two digits refer to the
approximate percentage content of the hydroxypropoxy group (OCH2CH(OH)CH3),
calculated on a dried basis. It contains methoxy and hydroxypropoxy groups conforming to
the limits for the types of hypromellose Molecular weight is approximately 10 000–1 500
000. The JP 2001 includes three separate monographs for hypromellose:
hydroxypropylmethylcellulose 2208, 2906, and 2910, respectively.

2.2.4 Structural Formula

Figure 3: Chemical structure of hypromellose

where R is H, CH3, or CH3CH(OH)CH2

2.2.5 Functional Category

Coating agent; film-former; rate-controlling polymer for sustained release; stabilizing agent;
suspending agent; tablet binder; viscosity-increasing agent.

2.2.6 Applications in Pharmaceutical Formulation or Technology

Hypromellose is widely used in oral, ophthalmic and topical pharmaceutical formulations. In
oral products, hypromellose is primarily used as a tablet binder, 34 in film-coating, 31-40 and
as a matrix for use in extended-release tablet formulations.41-45 Concentrations between 2%
and 5% w/w may be used as a binder in either wet- or dry-granulation processes. High-
viscosity grades may be used to retard the release of drugs from a matrix at levels of 10–80%
w/w in tablets and capsules.
Depending upon the viscosity grade, concentrations of 2–20% w/w are used for film-forming
solutions to film-coat tablets. Lower-viscosity grades are used in aqueous film-coating
solutions, while higher-viscosity grades are used with organic solvents. Examples of film-

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 Drug and Excipients Profile

coating materials that are commercially available include AnyCoat C, Spectracel, and
Pharmacoat. Hypromellose is also used as a suspending and thickening agent in topical
formulations. Compared with methylcellulose, hypromellose produces aqueous solutions of
greater clarity, with fewer undispersed fibers present, and is therefore preferred in
formulations for ophthalmic use. Hypromellose at concentrations between 0.45–1.0% w/w
may be added as a thickening agent to vehicles for eye drops and artificial tear solutions.
Hypromellose is also used as an emulsifier, suspending agent, and stabilizing agent in topical
gels and ointments. As a protective colloid, it can prevent droplets and particles from
coalescing or agglomerating, thus inhibiting the formation of sediments.
In addition, hypromellose is used in the manufacture of capsules, as an adhesive in plastic
bandages, and as a wetting agent for hard contact lenses. It is also widely used in cosmetics

2.2.7 Typical Properties

Table 1: Typical properties of Hypermellose according to different pharmacopeia

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2.2.8 Regulatory Status

GRAS listed. Accepted for use as a food additive in Europe. Included in the FDA Inactive
Ingredients Guide (ophthalmic preparations; oral capsules, suspensions, syrups, and tablets;
topical and vaginal preparations). Included in nonparenteral medicines licensed in the UK.
Included in the Canadian List of Acceptable Non-medicinal Ingredients.

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