UNIVERSITY OF BOTSWANA

Department of Health Science

Pharmacy
Pharmaceutics PHA 221-Assignement
Stability of Dosage Forms
Mompati Letsweletse
201100183
Date :05/06/2019
The Stability of Dosage Forms in Relation to Temperature, Hydrolysis, Photolysis, Solvolysis,
Hygroscopicity.

Stability of pharmaceutical product may be defined as the capability of a particular formulation

in a specific container/closure system to remain within its physical, chemical, microbiological
therapeutic and toxicological specification. Assurance that the packed product will be stable
for its anticipated self-life must come from an accumulation of valid data on the drug in its
commercial package. Pharmaceutical products are expected to meet their specification for
identifying purity, quality and strength throughout their defined storage period at specific
storage condition. The stability of dosage forms can be attributed factors such such
temperature, hydrolysis, photolysis, solvolysis and hygroscopicity. These factors inevitably
confer some degree of liability making dosage forms to be vulnerable to degradation. The
following section discusses the effects of the aforementioned factors on the stability if dosage
forms

Drugs with functional groups such as esters, amides, lactones or lactams may be susceptible to
hydrolytic degradation this is called Hydrolysis. It is the most commonly encountered mode
of drug degradation because of the prevalence of such groups in medicinal agents and the
ubiquitous nature of water

Procaine decomposes mainly by hydrolysis, the degradation being due primarily to the
breakdown of the uncharged and singly charged forms. The reaction of procaine is catalysed
by hydrogen and hydroxyl ions. Both the free base and the protonated form are subject to
specific base catalysis. Protection against hydrolysis can be ensured by Good packaging
practices like moisture resistant packs. E.g. strip packs stored in controlled humidity and
temperature conditions, even using desiccant such as silica gel. Buffering agents for pH control,
Alteration of dielectric constant and addition of complexing agents like caffeine Use of
Surfactants. Alcohol is found to slow hydrolysis because of the decrease in the dielectric
constant of the.

Photolysis is a solvolysis process in which drug molecules interact with water molecules to
yield breakdown products however with Solvolysis the solvent can be water or any
pharmaceutical cosolvent , in this type of reaction the active drug undergoes decomposition
following reaction with the solvent present .Usually the solvent is water but sometimes the
reaction involve pharmaceutical cosolvents .These solvents can act as nucleophiles, attacking
the electropositive centres in drug molecules .The most common solvolysis reactions

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encountered in pharmaceuticals are those involving “labile” carbonyl compounds such as
Esters (aspirin, alkaloids, dexamethasone sodium phosphate, estrone sulphate,Nitroglycerin),
lactones (pilocarpine and spironolactone) and lactams (penicillins,cephalosporins). Although
all the functional group cited are in principle, subject to solvolysis, the rates at which they
undergo this reaction may be vastly different.

In addition to Solvolysis and Hydrolysis there is Photolysis which is the process by which
light-sensitive drugs or excipient molecules are chemically degraded by light, room light or
sunlight. Ultra violet light causes more damage than red/orange light. The variation of
degradation depends on the wavelength of light, shorter wavelengths causes more damage than
longer wavelengths. Before a photolytic reaction can occur, the energy from light radiation
must be absorbed by the molecules. A photosensitizer is the drug or excipient molecule that
absorbs light energy. Two way in which photolysis can occur are: the light energy absorbed
must be sufficient to achieve the activation energy or the light energy absorbed by molecules
is passed on to other molecules which allow degradation to take place. In this process, light
may be the initiator while the reaction may be oxidation, polymerization or ring rearrangement.
Several photolytic reactions include: the decomposition of chlorpromazine hydrochloride, and
other phenothiazines, the darkening of morphine and codeine, the fading of tartrazine dye and
the initiation of numerous auto-oxidation processes.

Pharmaceutical products can be adequately protected from photo- induced decomposition by

the use of coloured glass containers and storage in the dark. Amber glass excludes light of
wavelength ˂470 nm and so affords considerable protection of compounds sensitive to
ultraviolet light. Coating tablets with a polymer film containing ultraviolet absorbers has been
suggested as an additional method for protection from light. A film coating of vinyl acetate
containing oxybenzone as an ultraviolet absorber has been shown to be effective in minimizing
the discoloration and photolytic degradation of sulfasomidine tablets.

Another factor which affect the stability of dosage forms is Hygroscopicity this is the capacity
of a product to react to the moisture content of the air by absorbing or releasing water vapour.
Moisture uptake or sorption is a significant concern for pharmaceutical powders. The extent of
sorption of water depends on the chemical nature of the drug. Two types of moisture sorption
are generally recognized: physical sorption and chemical sorption. Physical sorption is that

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which is associated with van der Waals forces and is reversible. Moisture has been shown to
have a significant impact on the physical, chemical, and manufacturing properties of drugs,
excipients, and formulations. It is also a key factor in decisions related to packaging, storage,
handling, and shelf life, and successful development requires a sound understanding of
hygroscopic properties. Hygroscopic drugs may require packaging with a desiccant in
containers that prevent moisture ingress

Temperature is also one of the primary factors affecting drug stability. High temperature
accelerate oxidation, reduction & hydrolysis reactions which lead to drug degradation. The rate
of oxidation of an organic compound is increased with increase in the temperature of storage.
For example: the rate at which hydroperoxides break down in to aldehydes, ketones and fatty
acids is accelerated at temperature in excess of 50℃. Temperature is an important parameter
because most reactions proceed faster at elevated temperatures than at lower temperatures

The rate constant temperature relationship has traditionally been described by the Arrhenius
equation

k=A*exp(-Ea/R*T)

Where k is the rate coefficient, A is a constant, Ea is the activation energy, R is the universal
gas constant, and T is the temperature (in kelvin). R has the value of 8.314 x 10-3 kJ mol-1K-.
The speed of many reactions increases about two to three times with every 10℃ rise in
temperature. Arrhenius equation explains the effect of temperature on rate of a reaction.
Energy of activation is defined as the minimum energy that a molecule should possess so that
molecular collisions produce the product. Arrhenius factor is defined as frequency of collisions
which can occur between molecules. A is the product of molecular collisions and probability
factor of collisions which give a product. Take logarithms both sides log k = log A –
Ea/2.303RT s. All the drug products are stored at suitable temperatures to avoid thermal
acceleration of decomposition. 3 varieties of temp. Suggested for storage of drug products.
Room temp, cool storage & cold storage

Finally, stabilizing pharmaceutical agents is critical for making acceptable products in the
industrial and community pharmacy setting. Therefore stabilization techniques, stability testing
protocols, and regulatory requirements must be understood clearly

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REFERENCES

Sinko, P. J., & Martin, A. N. (2006). Martins physical pharmacy and pharmaceutical sciences:
Physical chemical and biopharmaceutical principles in the pharmaceutical sciences.
Philadelphia: Lippincott Williams & Wilkins.

Banker, G. S., & Rhodes, C. T. (2002). Modern pharmaceutics. New York: Marcel Dekker.