KPJ HEALTHCARE UNIVERSITY

COLLEGE

BPH 1073 DOSAGE FORM DESIGN

AND DSIPENSING II

ASSIGNMENT : SUPPOSITORIES
AND PESSARIES

S.POONGUZHALI
NAME : SITI AMIRAH HAKIMAH BINTI MOHD FAIRUZ

NO. MATRIKS : 2062191008

BACHELOR OF PHARMACY (HONS)
PROGRAM :
COHORT 7
 With the help of at least two articles, explain the problems related to
the extemporaneous preparation of suppositories in hospital or
pharmacies.

Extemporaneous compounding is the preparation, mixing, assembling, packing and

labeling of a drug product or dosage form based on a prescription order from a licensed
practitioner for the individual patient whether in a pharmacy, clinic or in a hospital.

The pharmacist responsible for preparing or procuring an extemporaneously prepared

medicine should take responsibility for ensuring that the medicine is of suitable quality,
and is safe and efficacious. A failure to do so puts both the pharmacist and organization
at risk in terms of both civil and criminal liability. The pharmacist should also ensure that
the prescriber is aware of the unlicensed status of the medicine and any associated risks
with its use. Extemporaneous preparation should therefore only be considered when an
equivalent licensed product is unavailable or is unsuitable for use and if the use can be
clearly justified clinically and pharmaceutically. Consideration should be given to all
alternatives before choosing this option.

Suppositories are molded solid dosage forms intended for insertion into a body cavity.
They are used to deliver drugs for their local or systemic effects. Suppositories differ in
size and shape for each different route of administration which is rectal, vaginal, urethral
and nasal.

By prepared extemporaneously suppositories, there many advantages and

disadvantages. Choosing the suitable suppositories bases and vehicle used in the
dosage forms is crucial as the efficacy of the medicaments and the rate of diffusion is
depend on it. The suppository base has certain physical and chemical properties and has
a significant effect on the biopharmaceutical characteristics of the drug, dosing accuracy
and uniformity of API distribution. The old idea of a suppository base should melt at body
temperature has become outdated, for such bases are not necessary for therapeutic
action nor are they stable in warm climates. This might be a problem for pharmacist to
prepared extemporaneous suppositories.
Rectal drug administration is frequently known and utilized in pediatrics unit as the children
refused unpalatable medication. Hence, extemporaneous preparations of suppositories are
needed. However, errors during the extemporaneous manufacturing process can lead to
non-homogenous drug distribution within the dosage units that lead to adverse and side
effect of the patients. It shows that the most frequent technological error extemporaneous
preparations of suppositories are occurs when the pharmacist fails to use the correct
displacement factor in the calculations which could lead to a 4.6% increase or decrease in
the assay in individual dosage units which is known as dosage uniformity problems.

According to USP, the compounded preparations are to be prepared to ensure that each
preparation shall contain not less than 90.0% and not more than 110.0% of the theoretically
calculated and labeled quantity of active ingredient per unit weight or volume, and not less
than 90.0% and not more than 110.0% of the theoretically calculated weight or volume per
unit of the preparation. Additionally, a representative number of suppositories should weigh
not less than 90% and not more than 110% of the average weight of all suppositories in
the batch. The second source of error can occur when the molding excess is calculated
solely for the suppository base. This can further dilute the final suppository drug
concentration causing the assay to be as low as 80%.

In the old times, suppositories were made by pouring the medicated melted cacao butter
into paper cones that rested in the mouths of wide-mouth bottles of appropriate size. This
empirical and defective method was improvise with new metal mold which had the
advantage of not absorbing either the cacao butter or the medicine. However, this mold
has the disadvantage of sticking to the hardened suppositories, rendering it difficult to
remove them.

Other better and efficient method was used by putting the mold, before filling, on a cake
of ice until it was thoroughly chilled, then breathing into the mold, which would deposit on
its inner surface drops of water similar to moisture produced when the breath is blown upon
a chilled window pane. Be it said that dipping the mold into water did not answer the
purpose, mainly because of the fact that it was so difficult to remove the last traces of oil
from previous manipulations. To this film of oil, the water would not adhere, the fault being
overcome by the deposit, in minute drops, of the vapor of the breath, which made an
adhesion and perfect coat of water over the metal, preventing the mold from touching the
suppository.
Suppositories were recommended to be stored under refrigeration to prevent substantial
prolongation of liquefaction time. If appropriate, a “refrigerate” label should appear on the
container regardless of the base or medication used in the formulation. Suppositories
should be protected from heat and should be stored in a refrigerator, but should not be
frozen. Hygroscopic base such as glycerin and PEG-based suppositories should also be
protected from moisture as it tends to absorb moisture from the air. The patient should be
instructed to store the suppositories in a cold dry place. The recommended packaging of
suppositories is individually wrapped or dispensed in the disposable molds in which they
are prepared.

If they are not packaged properly, they may become deformed, stained, broken, or chipped.
Other than that, suppositories also recommended to properly packaged by using sealed
individual disposable molds. This type of packaging is ideal to minimize direct product
contact to external environment that may enhance product’s instability and to prevent any
microbial activity contaminations

Compounded extemporaneous suppositories has a varied shelf-life from a minimum of 3

months to a maximum of 1 year after compounding. If the expiration dating of some
products was not provided on the label, it is violated Good Compounding Practices in
labelling requirements. For stability purposes of extemporaneous preparations of
suppositories, USP recommends that the label on the container or package of an official
compounded preparation must bear a beyond-use date, based on published data, or
appropriate testing, or USP-NF standards for most compounded suppositories.

Product that has the longest shelf-life of 1 year should be packaged in a wide mouth, amber
plastic bottle without proper individual wrap. It is to prevent any possible contaminations
from microbial activities due to multiple uses of the product. Stability of this product
throughout its shelf-life could be questioned since it was not properly packaged and does
not have a proper and specified recommended storage condition.

Most compounded suppositories were either bullet or cone shaped, which were also
suitable for vaginal delivery. The product texture was varied ranging from soft to brittle,
depending on the type of suppository base used in the formulation. Since suppositories
from most of the pharmacies investigated were properly packaged in individual disposable
molds, the product shape was consistently maintained without chips or cracks.
However, there is a product which was improperly packaged, had suppositories that were
deformed or chipped. In addition, pH of the extemporaneous prepared suppositories is
important as suitable and closer range of pH of the final product will minimize irritation to
the rectal and vaginal mucosa caused by contact with the product.

The extemporaneous suppositories should have characteristics that been preserved to

prevent contamination from the bulk ingredients prior to preparation of the product, during
consumer use, and throughout the product’s shelf-life. Several factors can influence the
preservative activity, such as concentration of preservative, pH, temperature, formulation
composition, containers and closures, microorganisms and organic matter.

It is not strange and surprising for suppositories that are extemporaneously compounded
to not contain any preservatives or antioxidants, especially when water is excluded from
the formulation, a non-oxidizing base is used or the drug is stable in the dosage form for
the proposed short shelf-life. Nevertheless, it is stated before that the accurate shelf-life
should be based on stability studies conducted with the drug product stored in the primary
dispensing container in a realistic environment.

Beside that, when two or more drugs are combined in a single suppository, the absorption
characteristics of one drug may counteract and interact with one and other. One drug may
be absorbed adequately and the other drug remain in the rectal fluids. Thus, drug
combinations should be avoided in extemporaneous compounding of suppositories but it
is possible to prescribe medicinal substances with various pharmacological and physical
and chemical properties.

For example, by using combinations are appropriate and promising from a pharmacological
point of view, by preparing suppositories of combined action as active ingredients is
possible. For the preparation of suppositories of hydrophobic bases, method of
administration of active substances was highlight in order to preserve their pharmacological
properties and increase the rate of their release.
To increase the bioavailability of water-soluble and insoluble API in suppositories on
hydrophobic bases, it is advisable to use solubilizers that increase the thermodynamic
activity of active components in the stratum corneum and increase their penetration through
the skin and mucous membranes. Based on the article, it was suggested that, in addition
to calendula oil, use the following hydrophilic solvents: propylene glycol and glycerol in
enthonium. It has been proved that the use of propylene glycol as a solubilizer contributes
to an increase in the degree of ethonium release and, therefore, increases the therapeutic
effect of the drug.

Also, from the results shown, the most intense release of ethonium occurs during the first
30 minutes, which is very important given the time that the suppository is in the city of
introduction. Based on the complex of physical and chemical and biopharmaceutical
researches, the composition of extemporal suppositories of combined action was
developed. Biopharmaceutical studies have proved that the intensity of release of the
active substance is maximal when using a solubilizer for its dispersion.

Overall, to sum up, it was crystal clear that the quality of extemporaneously compounded
drug delivery systems was inconsistent from pharmacy-to-pharmacy. Extemporaneous
compounding practice in a pharmacy setting is still exists aimed at providing suitable
dosage forms for patients with special needs and the product should attributes, including
content uniformity and potency, pH, preservative effectiveness testing and microbial
testing, are each critical factor that must be precisely controlled for reproducible delivery of
active pharmaceutical ingredients.

Prescribing of extemporaneous medicines to meet this unmet medical need is accepted

part of pharmacy practice, and it seems likely that pharmacists will continue to be required
to prepare extemporaneous products. Medicine regulatory agency efforts to create
appropriate standard need to be initiated and implemented. Furthermore, pharmacists
need to have access to stability, compatibility, and formulation information as well as
appropriate training to ensure patients are supplied with high quality, safe, and effective
preparations. By established quality control tests for extemporaneously compounded drug
delivery systems, including vaginal suppositories can ensure that the highest quality
product is dispensed to patients without any hassle.
 REFERENCES

Allen, L. V. (1997). Suppositories as drug delivery systems. Journal of Pharmaceutical

Care in Pain & Symptom Control, 5(2), 17-26.

Bervinov, Y. A., & Azarenko, Y. M. (2018). Development of composition and technology

of extemporaneous suppositories for the treatment of the hemorrhoids.

Kalmar, E., Lasher, J. R., Tarry, T. D., Myers, A., Szakonyi, G., Dombi, G., ... &
Alexander, K. S. (2014). Dosage uniformity problems which occur due to
technological errors in extemporaneously prepared suppositories in hospitals and
pharmacies. Saudi Pharmaceutical Journal, 22(4), 338-342.

Mahaguna, V., McDermott, J. M., Zhang, F., & Ochoa, F. (2004). Investigation of
product quality between extemporaneously compounded progesterone vaginal
suppositories and an approved progesterone vaginal gel. Drug development and
industrial pharmacy, 30(10), 1069-1078.

Nanjwade, B. (2017, March 21). Preparations in pharmacy of hospital.

https://www.slideshare.net/bknanjwade/preparations-in-pharmacy-of-hospital-
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Rusho, W. J. (1996). Clinical issues and concerns in the use of extemporaneously

compounded medications. Journal of Pharmaceutical Care in Pain & Symptom
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