Research & Development (R&D) – Formulation

Pharmaceutical formulation is the process of combining different chemical

substances with the active drug to form the final medicinal product. It is obtained after
in-depth study of physical, chemical, and mechanical properties of the drug substance.
It’s main objective is to produce a final medicinal product that is stable and acceptable
to the patient. In developing a drug, there are few considerations that is needed to be
taken which is the physical, chemical, and mechanical properties of drug.
Generally, these are the roles of formulation research and development services:

 To develop generic products in various dosage forms

 To manufacture Good Manufacturing Practice (GMP) batch
 To prepare all necessary registration documents for product
 Registration according to regulatory requirements.
 To support for product technology transfer

Pre-formulation Development

Before starting the preformulation studies, we should know the properties of

the drug, potency relative to the competitive products and the dosage form, literature
search providing stability and decay data, the proposed route of drug administration,
literature search regarding the formulation approaches, bioavailability and
pharmacokinetics of chemically related drugs.

Once a pharmacologically active compounds has been identified, a project team

consisting of representatives from the disciplines has responsibility for assuring that
the compound enters the development process in its optimum molecular form. The
sources for literature review during preformulation studies may be from Malaysian
Brand Leader Product or Reference Listed Drug (FDA Orange Book) or Electronic
Medicine Compendium where this source is used regarding innovator products. In
finding out other competitor products, we can use MIMS, NPRA (Quest 3) or market
survey. In addition to these, searching through journals, books or articles related to
product to be developed can also be done.

A Reference Listed Drug (RLD) which is an FDA approved drug product can be
referred to by a generic drug manufacturer while filing an Abbreviated New Drug
Application (ANDA). It is useful to establish bioequivalence of the product with that
of an already approved one by determining the following details in drug development:

 Product name
 Active pharmaceutical ingredient (API)
 Strength and dosage form
 Packaging and pack size
 Manufacturer
 Manufacturing and expiry date
 Physical properties - appearance, tablet weight, dimension, hardness,
 disintegration time, friability, coating type and dissolution
Next, it will be followed by characterization of API, selecting the right excipients
based on its functions, where the percentage usage shall be compendial in Handbook
of Pharmaceutical Excipients/Drug Registration Guidance Documents (DRGD).
Lastly, compatibility study of API-excipient need to be determine as interaction
between API and excipients may affect the assay of API and causing presence of
undesired degradation products

Formulation development

Formulation trial batch can be conducted to optimize the formula and manufacturing
process. Stability studies allow evaluation of API stability under the influence of a
variety of environmental and data from these studies enable recommended
storage conditions, retest intervals and shelf lives to be established. Pilot batch
manufacturing involved at least least 1/10 of the commercial batch size. Meanwhile,
Review Batch Manufacturing Record (BMR) and Batch Packaging Record (BPR)
helps to monitor manufacturing process. Lastly, for registering products, dossier
needs to be prepared involving all necessary related documents of product technical
dossier according to regulatory requirements such as following:
 Pilot Batch Report
 Product Development Report
 Calculation of restricted excipients (menthol, saccharin sodium)
 Drug Master File (DMF) of API.
(545 words)