A Simple Guide for Beginners in Pharmaceutical R&D

ONE
Formulation development should always begin with understanding the drug substance. Before selecting any excipient, the scientist must know whether the API is soluble or insoluble, acidic or basic, hygroscopic or stable, and whether the dose is low or high.

TWO
The reference product should be studied in detail. Its dosage form, strength, release behavior, labeling claims, packaging, and storage conditions provide valuable insight into how the product is designed to perform.

THREE
A clear development strategy must be defined early. Decisions such as IR versus MR, simple formulation versus complex technology, and generic versus differentiated product determine cost, timelines, and regulatory expectations.

FOUR
Excipients should be selected during early trials. Pharmacopeial and commonly used excipients with established regulatory acceptance should always be preferred.

FIVE
The first trial batch is meant for learning, not success. Its purpose is to observe powder flow, compressibility, granulation behavior, and basic tablet formation.

SIX
Initial evaluation should focus on basic physical parameters such as weight variation, hardness, friability, and disintegration. If these fundamentals fail, dissolution success is unlikely.

SEVEN
Dissolution testing should be performed only after basic tablet quality is acceptable. At this stage, the objective is to understand release direction, not to achieve perfect profile matching.

EIGHT
Problems must be identified clearly and scientifically. Instead of stating that the formulation failed, the exact issue should be defined, such as poor dissolution, content variability, sticking, or slow disintegration.

NINE
Only one variable should be changed at a time.

TEN
Every batch should be treated as a learning experiment. Improvements, failures, and unexpected outcomes must be documented, as development knowledge is more valuable than immediate success.

ELEVEN
After multiple trials, non-performing excipients should be eliminated and effective components retained. This helps narrow the formulation toward consistency and robustness.

TWELVE
Scientific tools such as QbD, risk assessment, and Design of Experiments should be applied only after formulation behavior is understood. These tools are meant for optimization, not trial-and-error development.

THIRTEEN
Scale-up behavior must be evaluated carefully. Mixing intensity, granulation time, drying conditions, and lubrication sensitivity often change significantly from lab to pilot scale.

FOURTEEN
Stability thinking should begin early in development. Moisture sensitivity, oxidation risk, light sensitivity, and packaging suitability must be considered from the initial formulation stage.

FIFTEEN
Once reproducible performance is achieved, the formulation and process are locked. This becomes the basis for exhibit batches, bioequivalence batches, and regulatory submissions.

Read also: CPP and CQA in Different Stages of Drug Product Manufacturing

Resource Person: Moinuddin Syed. Ph.D, PMP®