DEVELOPMENT
OF DOSAGE
FORMS
Four Stages of Pharmaceutical Product
Development:
Preformulation,
Prototype Development and Scale-Up,
Biological Aspects, and
Commercialization
The PREFORMULATION STUDIES refer to the studies done at the early stages of
the development process of drug candidates into different dosage forms. Investigation
of both the physical and chemical properties of these candidates are achieved during
the preformulation stage in order to identify the critical features that affect the selection
of the most appropriate candidate .
Preformulation studies have been
reported to act as accurate
predictors that effectively predict the
changes that may be associated
with the combination process of the
active pharmaceutical ingredient
(API) with a suitable delivery system
that is intended to safely and
effectively deliver the active
ingredient to the patient.
Preformulation studies are usually
Pure Drug free from
classified into three main phases,
residual impurities
Three phases of preformulation studies.
as…
Preformulation studies
have been shown to play
an important role during
processes of drug
discovery and
development since these
studies are usually relied
on when valuable
information is needed
regarding stages of lead
identification and
optimization. The role of
the data collected during
the preformulation
studies varies based on
the different groups
involved in the discovery
and development stages.
Different groups
in a drug’s
discovery and
development
stages.
PROTOTYPE DEVELOPMENT : The prototype development is an important stage
during the development of a new product that represents the primary working model of
the product which will then be perfected in the form of the final product. Basically,
there are four phases of prototype development.
BIOLOGICAL ASPECTS IN PHARMACEUTICAL PRODUCT DEVELOPMENTThe Preclinical Tenure and Strategies:
Three essential parts are involved in the preclinical stage of drug development. The
first part focuses on the in vitro models and their importance in the preclinical stage,
whereas the second part provides a brief discussion about the application of new in
silico models and how simulation prediction has aided in the efficiency of the drug
development process, and the last part covers the issue of using animals as models for
testing some properties of the newly-synthesized drugs.
The use of in vitro models usually provides information in the early stage of preclinical
development regarding probable biological performance of the drug product. It is
proven that data obtained by these models provide very useful information to be further
used for in vivo testing. In vitro methods have to be validated. This will aid in the
characterization of the drug formulation more properly before the drug is given to
humans.
In Silico Models and Simulation Predictions- Computational prediction models are
shown to have an observable role in modern medicinal chemistry since these models
offer a high potential to transform the drugs’ early research phases, in terms of saving
both time and cost.
In silico methods of prediction and assessment are of a noticeable importance because
the lack of such models would make it very difficult and even impossible to assume all
factors affecting the prediction by in vitro/in vivo models.
Researchers are shifting from applying principles of random screening into methods
that are more rational. This has shown to have a direct effect on the rate of success of a
new chemical entity (NCE) development and, hence, improve the productivity of the
pharmaceutical research and development. Nowadays, virtual screening models are
considered as essential components in the modern process of drug discovery. .
Computational tools are also playing a critical role in medicinal chemistry programs.
Similarly, various computational tools are available to predict API’s
solubility/miscibility/or possible reaction with single or mixture of raw materials. With time
such tools will become necessary to develop a drug product to save resources, like time
and money.
The Use of Animal Models
It is known that testing pharmaceutical formulations directly in humans is an
unaffordable and unethical process. Thus, the establishment of in vivo in vitro
correlation (IVIVC) is essential for the prediction of the performance of such
formulations in humans, which may, therefore, minimize the risk of failure in the firstin-human (FIH) studies. Animal models that are commonly used in the pharmaceutical
field include rats, guineapigs, dogs, and monkeys. These animal models are used for
the evaluation of the performance of the newly-formulated drug product before testing
in humans. Many new pharmacokinetic software designed on physiologic bases, such
as GastroPlus and PK-SIM, are being applied for testing the behavior of new
formulations. The quality of such software is dependent on how precise the input data
is. However, the awareness regarding the inability of animal models to reliably predict
formulations’ behavior in clinical trials is increasing. Despite the wide use of mice, they
are still considered as poor models for most human diseases.
COMMERCIALIZATION ASPECTS IN PHARMACEUTICAL PRODUCTS
DEVELOPMENTPatents, Exclusivity, and Evergreening Strategies…Must
Commercial success of pharmaceutical companies is widely dependent on the
activities during the stages of research and development. These activities usually
provide information regarding the efficacy, safety, as well as the tolerability of drugs to
the regulatory agencies.
CONCLUSION- There are a number of emerging trends in the field of
pharmaceutical industry development, such as the Pharmacovigilance,
pharmacogenomics, drug repositioning, and the use of cell lines and
cultures of human origins. Drug commercialization and the challenges
facing the pharmaceutical companies are now focused on the field of
pharmaceutical research and development.
Drug repositioning - the use of a drug in an indication other than the
one for which it was initially marketed, is a growing trend.