Pharmaceutical formulation
Pharmaceutical formulation, in pharmaceutics, is the process in which different chemical substances are combined to a pure drug substance to produce a final medicinal product.
Formulation studies involve developing a preparation of the drug which is both stable and acceptable to the patient. For orally taken drugs, this usually involves incorporating the drug into a tablet or a capsule. It is important to appreciate that a tablet contains a variety of other substances apart from the drug itself, and studies have to be carried out to ensure that the drug is compatible with these other substances.
Preformulation involves the characterization of a drug's physical, chemical, and mechanical properties in order to choose what other ingredients should be used in the preparation.
Formulation studies then consider such factors as particle size, polymorphism, pH, and solubility, as all of these can influence bioavailability and hence the activity of a drug. The drug must be combined with inactive additives by a method which ensures that the quantity of drug present is consistent in each dosage unit e.g. each tablet. The dosage should have a uniform appearance, with an acceptable taste, tablet hardness, or capsule disintegration.
It is unlikely that formulation studies will be complete by the time clinical trials commence. This means that simple preparations are developed initially for use in phase I clinical trials. These typically consist of hand-filled capsules containing a small amount of the drug and a diluent. Proof the long-term stability of these formulations is not required, as they will be used (tested) in a matter of days. Consideration has to be given to what is called the drug load - the ratio of the active drug to the total contents of the dose.
A low drug load may cause homogeneity problems. A high drug load may pose flow problems or require large capsules if the compound has a low bulk density.
By the time phase III clinical trials are reached, the formulation of the drug should have been developed to be close to the preparation that will ultimately be used in the market. Knowledge of stability is essential by this stage, and conditions must have been developed to ensure that the drug is stable in the preparation. If the drug proves unstable, it will invalidate the results from clinical trials since it would be impossible to know what the administered dose actually was. Stability studies are carried out to test whether temperature, humidity, oxidation, or photolysis (ultraviolet light or visible light) have any effect, and the preparation is analysed to see if any degradation products have been formed.
It is also important to check whether there are any unwanted interactions between the preparation and the container. If a plastic container is used, tests are carried out to see whether any of the ingredients become adsorbed on to the plastic, and whether any plasticizers, lubricants, pigments, or stabilizers leach out of the plastic into the preparation. Even the adhesives for the container label need to be tested, to ensure they do not leach through the plastic container into the preparation.
Unither has knowledge in formulation development for more than 20 years. Unither offer:
- formulation development from to industrial transfer and process validation
- clinical batch manufacturing service
- comprehensive manufacturing, analytical and development documentation
- project advice and management via a dedicated project manager
- a trained and qualified multi-disciplinary technical team
- EU approved pharmaceutical manufacturing site
- Continuous cGMP quality improvement programs
- Continuous enhancement of quality levels due to the manufacturing of clinical batches
Unither has an international experience and deals already with several major pharmaceutical company
The dosage forms that Unither can develop :
- solid dose (tablets, capsule, effervescent)
- liquids (stick packs, syrup, suspension, solutions, emulsions)
- semi-solids (creams, gels, suppository)
- eyewash and eye lotions
Unither’ services:
- excipients selection
- formulation optimization
- scale-up and manufacturing process optimization
- pilot and stability batches manufacturing
- clinical batch manufacturing
- technical support for industrial transfer
- formulation studies for clinical trials placebo products
For solid dose the batch sizes are from 1 kg to 50 kg:
- plain tablet, sugar or film coated, modified release
- effervescent tablets
- all-size of hard capsules with compression metering
- sachets: paper, aluminium, polyethylene
- process
- dry blending
- aqueous and non aqueous granulation
For Liquids the batch sizes are up to 50 litres
- stick pack and standard sachet
- oral solutions, syrups, suspensions
- creams and gels
Unither facilities have 4 separate processing boxes with individual airlocks and one box for development activities with separate humidity and temperature controls.
