Pharmaceutical formulation
Pharmaceutical formulation, in pharmaceutics, is the process in which different chemical substances, including the active drug, are combined to produce a final medicinal product. The word formulation is often used in a way that includes dosage form.
Stages and timeline
Formulation studies involve developing a preparation of the drug which is both stable and acceptable to the patients. For orally administered drugs, this usually involves incorporating the drug into a tablet or a capsule. It is important to make the distinction that a tablet contains a variety of other potentially inert substances apart from the drug itself, and studies have to be carried out to ensure that the encapsulated drug is compatible with these other substances in a way that does not cause harm, whether direct or indirect.
Preformulation involves the characterization of a drug's physical, chemical, and mechanical properties in order to choose what other ingredients (excipients) should be used in the preparation. In dealing with protein pre-formulation, the important aspect is to understand the solution behavior of a given protein under a variety of stress conditions such as freeze/thaw, temperature, shear stress among others to identify mechanisms of degradation and therefore its mitigation.[1]
Formulation studies then consider such factors as
It is unlikely that formulation studies will be complete by the time
By the time
Container closure
Formulated drugs are stored in container closure systems for extended periods of time. These include blisters, bottles, vials, ampules, syringes, and cartridges. The containers can be made from a variety of materials including glass, plastic, and metal. The drug may be stored as a solid, liquid, or gas.
It's important to check whether there are any undesired interactions between the preparation and the container. For instance, if a
Formulation types
The drug form varies by the route of administration. Like capsules, tablets, and pills etc.
Enteral formulations
Oral drugs are normally taken as tablets or capsules.
The drug (
Tablet
A tablet is usually a compressed preparation that contains:
- 5-10% of the drug (active substance);
- 80% of glidants, and binders; and
- 10% of compounds which ensure easy intestine.
The dissolution time can be modified for a rapid effect or for
Special coatings can make the tablet resistant to the
Pills can be coated with sugar, varnish, or wax to disguise the taste.
Capsule
A capsule is a gelatinous envelope enclosing the active substance. Capsules can be designed to remain intact for some hours after
Sustained release
There are a number of methods by which tablets and capsules can be modified in order to allow for sustained release of the active compound as it moves through the
Another method by which sustained release is achieved is through an
Parenteral formulations
These are also called injectable formulations and are used with
Many
Most protein formulations are parenteral due to the fragile nature of the molecule which would be destroyed by enteric administration. Proteins have tertiary and quaternary structures that can be degraded or cause aggregation at room temperature. This can impact the safety and efficacy of the medicine.[3]
Liquid
Liquid drugs are stored in
As with solid formulations, liquid formulations combine the drug product with a variety of compounds to ensure a stable active medication following storage. These include solubilizers, stabilizers,
If concentrated by
Lyophilized
Lyophilized drugs are stored in vials, cartridges, dual chamber syringes, and prefilled mixing systems.
Before administration, a lyophilized drug is reconstituted as a liquid before being administered. This is done by combining a liquid diluent with the freeze-dried powder, mixing, then injecting. Reconstitution usually requires a reconstitution and delivery system to ensure that the drug is correctly mixed and administered.
Topical formulations
Cutaneous
Options for topical formulation include:[5]
- Cream – Emulsion of oil and water in approximately equal proportions. Penetrates stratum corneumouter layers of skin well.
- Ointment– Combines oil (80%) and water (20%). Effective barrier against moisture loss.
- Gel – Liquefies upon contact with the skin.
- Paste – Combines three agents – oil, water, and powder; an ointment in which a powder is suspended.
- Powder – A finely subdivided solid substance.
See also
References
- ^ Simler, R., Walsh, G., Mattaliano, R.J., Guziewicz, N., and Perez-Ramirez, B. (2008). Maximizing Data Collection and Analysis During Preformulation of Biotherapeutic Proteins. BioProcess International 6(10), 38-45.
- ^ M. Nocent, L. Bertocchi, F. Espitalier, M. Baron and G. Couarraze. (2001). Definition of a solvent system for spherical crystallization of salbutamol sulfate by quasi-emulsion solvent diffusion (QESD) method. Journal of Pharmaceutical Sciences 90 (10), 1620-1627.
- ^ Chang, B.S. and Hershenson, S. 2002. Practical approaches to protein formulation development. in "Rationale Design of stable protein formulations-theory and practice" (J.F. Carpenter and M.C. Manning eds.) Kluwer Academic/Plenum publishers, New York, pp. 1-25
- ^ Rationale Design of Stable Lyophilized Protein Formulations: Some Practical Advice, Carpenter et al, Pharmaceutical Research, Vol 14, No.8, 1977
- ^ "Doctor, why are you prescribing an ointment?". American Academy of Dermatology.