ICH GUIDELINES FOR ASSESSMENT OF
HERBAL DRUGS
Introduction
The Quality, safety and efficacy of herbal drugs remain major issues of concern especially
in the developing world where the use is high. The evaluation of herbal drugs involves
confirmation of its identity, quality, purity and detection of nature of adulteration. Thus,
the evaluation parameters are based upon physical, chemical, microbiological, therapeutic
and toxicological studies. It also serves as an important tool in stability studies.
CONFORMITY AND CONTRAVENTION WITH
RECOMMENDED STABILITY CONDITIONS
Drugs regulatory bodies recommend that a drug product should be subjected
to accelerated stability testing (at 40 °C/75% RH) for 6 months, intermediate
stability testing (at 30 °C/65% RH) for 6–12 months and long term stability
testing (at 25–30 °C/60–75% RH) for a period equal to the proposed shelf life
of the product.
Intermediate stability testing is, however, not required when the conditions
for long-term testing are same as those for intermediate ones (ICH, 2003).
STABILITY TESTING OF HERBAL DRUGS
Stability testing is required to determine the shelf life and assign expiry dates to medicines
Herbal drugs may be single active constituent or entire herb or combination of herbs
consisting of mixture of constituents. Most of herbal drug products used are group of
constituents.
Stability testing of herbal products is a complicated issue because the entire herbal product
is regarded as the active substance, regardless of whether constituents with defined
therapeutic activity are known.
Trace metals contamination leaching from the container, etc., and also provides statistics
for determination of shelf life.
The stability testing of herbal products includes checking the quality which varies with
the time under the influence of environmental factors, such as temperature, humidity,
light, oxygen, moisture, other ingredient or excipients in the dosage form, particle size
of drug, microbial contamination.
Therefore evaluation of the parameters based upon chemical, physical, microbiological,
therapeutic and toxicological studies can serve as an important tool in stability studies.
PROBLEMS RELATED TO THE HERBAL
PRODUCT STABILITY
PHYSICAL INSTABILITY
Natural medicines are usually prone to physical instability due to presence of
impurities and reaction with the container. Conditions like growth of the
micro-organisms and insect feeding affect the secondary metabolites and
chemical composition of plants.
Volatile active components of natural medicine have the problem of volatility
and decreasing activity during storage for a long time.
ENVIRONMENTAL CONDITIONS
Environmental conditions such as rainfall, altitude, temperature, soil, storage
conditions as well as different harvesting procedures, time and method of
collection, manufacturing processes such as selecting, drying, purifying,
extracting and genetic variability can create substantial variability in the
product quality, stability and in the concentration of plant constituents.
Light is also an important factor affecting phytomedicines by generating free
radicals
CHEMICAL INSTABILITY
Herbal drugs are subjected to degradation during storage by oxidation, hydrolysis,
crystallization, emulsion breakdown, enzymatic deterioration and chemical reactions with
the additives & excipients. Temperature & Moisture are the two major factors that affect
quality & stability of a herbal product.
A chemical reaction increases by 2 to 3 fold for every 10ºC rise in temperature.
Moisture absorbed on to the surface of solid drug often increases the rate of
decomposition if it is susceptible to hydrolysis.
Presence of enzymes in the product also increases the rate of chemical degradation.
COMPLEX MIXTURE VARIABILITY AND INCONSISTENCY
Herbal formulation are complex mixtures of different components obtained during
extraction process. Each component has variable shelf life, activity, concentration and
consistency.
It creates a problem during storage condition determination as it is not easy to
determine the stability of final herbal preparation based on the activity and stability
profile of a single component.
DRUG INTERACTION DETERIORATION DECOMPOSITION AND
STORAGE
Moisture content above the critical value and mould growth in natural products can
cause the interactions of the active components with the packaging materials and with
the other ingredients of formulations used such as additives cause alterations in the
novel drug activity.
Stability studies performed on at least three production batches for the proposed shelf
life, denoted as long term stability and is performed under natural atmospheric
conditions with the analytical techniques like spectrophotometry, HPLC, HPTLC and by
employing proper guidelines.
it is possible to generate a sound stability data of herbal products and predict their shelf
life, which will help in improving global acceptability of herbal products.
ROLE OF MARKERS IN DETERMINING THE STABILITY OF HERBAL
DRUGS
Markers are chemically known compounds, which may or may not have the
therapeutic effect, they are used to calculate the quantity of herbal medicinal
ingredients in herbal medicinal products.
It is important to isolate and structurally elucidate chemically defined substances in
plants, drug and / or drug preparations so that they can be used as markers that not
only help to better understand the active principles of herbal drugs but also can
enhance analytical quality control.
METHODS TO DEAL WITH HERBAL DRUG INSTABILITY
Determination of the Physical Parameter
Depending on type of preparation, sensory properties, physical constants,
moisture, ash content, solvent residues & adulteration have to be checked
to prove identity and purity microbiological contamination and foreign
materials such as heavy metals, pesticides residues, alfatoxins &
radioactivity also need to be tested.
To prove the constant composition of herbal preparations, appropriate
analytical methods have to be applied and different concepts have to be
used in order to establish relevant criteria for uniformity.
ANALYTICAL METHODS TO DETERMINE STABILITY OF HERBAL DRUGS
The analysis of herbal preparations is mostly done by modern chromatographic or
spectroscopic methods like HPLC, gas Chromatography (GC), TLC, Quantitative
determinations by UV visible spectroscopy or combinations of these.
HPLC and GC methods can be used for identification and purity testing, as well as the
detection of single compounds for assay is possible during one analysis. LC and GC
mass coupling are also the tools for determinations.
Determination of the impurity profile
This technique helps in the identification of impurities that result from degradation of active
constituents. The active constituents are subjected to a known degradation process and the
degradation products are identified.
Degradation may be due to oxidation, reduction or hydrolysis hence we can have an idea of
what could be the degradation products. These can be listed and kept as a reference library of
degradation products.
For routinely doing an impurity profile, this library can be referred and the nature and
structure of the impurity can be traced.
Since impurities decreases the stability of the natural medicines, it is important to note the
type of impurities. It can be done by the analytical methods as HPLC, TLC, capillary
electrophoresis, spectrophotometry, GC, MS etc.,
Identification and quantification of all metabolites
Nonbiased identification and quantification of all metabolites in herbal or other natural
products is vital to determine the status and stability of the complex mixtures.
IR spectroscopy in combination with chemometric data processing could provide total
metabolic fingerprint profile of phyto-formulations.
Controlled storage conditions:
Control measure to protect against deterioration includes the use of airtight container made of
materials that will not interact physically or chemically with the material being stored.
Storage in ventilated cool, dry area and periodic spraying of the stored area with insecticide
will help to prevent the spread of infestation.
Influence of environmental factors such temperature, light, oxygen, moisture, other ingredient
or excipients in the dosage form particle size of drug, microbial contamination, trace metal
contamination, leaching from the container etc., should be established to recommend proper
storage conditions.
