Pharmaceutical Drug Formulation

 

The term used to define the process in pharmaceutical studies, involving the combination of chemical components, including the active drug and the excipients, for the production of a medicinal product, is known as formulation. The term formulation is sometimes also used to define a particular dosage form.

Stages involved in the process of formulation:

Study of pharmaceutical Drug Formulation involves the development of a preparation or formula of the drug that is the most stable and compatible with the patient's body, as well as fulfills the needs and therapeutic requirements of the patient.  The preparation of orally administered drugs usually involves the incorporation of drug material into a tablet or capsule. It is important to know that a tablet or capsule contains a number of chemical substances other than the active ingredient, and it is important to make sure that the compatibility of encapsulated drug with other components is in such a way that all the drug components are beneficial to the patient and pose no harm to the user, either directly or indirectly.The various steps involved in the process of formulation are as follows:

Pre formulation:

The first step or pre formulation involves the characterization process in which the various physical, chemical and mechanical properties of different components are determined in order to choose the ingredients for the preparation.

For example, in pre formulation of protein, it is important to understand the solution behavior of the particular protein in different conditions of stress such as frosting or defrosting, heat, or shear stress. This study allows the identification of mechanisms of degradation of protein and ways to avoid the degradation risks.

Production of Dosage form:

After the determination of basic properties, the next step in formulation is the consideration of factors such as particle size, polymorphism, pH, viscosity and solubility. These are important to be determined as all these factors have important influence on the bioavailability and the therapeutic activity of the drug. The active ingredient of the drug is then combined with excipients (inactive ingredients) by following a suitable method that ensures a consistent quantity of drug in each unit of the dosage form. The final product should have a uniform consistency, elegant appearance, acceptable taste, sufficient hardness and reasonable disintegration ability.

Container Closure:

The formulated drug is then stored in container Closure system for long term storage. A number of different packing options are available. These include blisters, bottles, vials, ampules, syringes, cartridges, tubes etc. The material of container could be made of plastic, glass or metal. The drug could be stored in any physical state (solid, liquid or gas).

While packing, it is important to know if any undesirable interaction exists between the drug and the container. For example, if a plastic container is being used, tests are carried out to determine if the ingredients of the formulation have the ability to be adsorbed on the plastic surface or if any pigment, plasticizing agent, lubricating agent or stabilizer has the potential to leach out of the plastic into the formulation. Even the adhesives used for the label container are tested to make sure that no ingredient leaches out into the Formulation through the plastic container.

Counterfeiting:

Counterfeiting drugs are a serious problem these days. Due to the identical appearance of different drugs, patient might be unknowingly taking a totally useless drug that may be causing more harm than any therapeutic effect. Customized packaging, labels of authentication, holograms, and security prints could be an important part of the entire security of the drug formulation system. These processes allow the verification of the drug enclosed in a package and ensure that the packaged drug is what the label says. Drug and packaging counterfeits can be very sophisticated at times and require high level of vigilance to avoid the occurrence of such incidences and to ensure safe delivery of drugs to the community.                                                         

Types of Formulation:

The forms of drugs vary according to their route of administration. Different types of formulations used as oral, ophthalmic, inhalation, parenteral, topical or suppositories, are as follows:

Oral formulations:

Oral formulations are those that are meant to be taken orally and pass through the Gastrointestinal Tract (GIT) to be distributed throughout the body.

These formulations include the following products:

Pills (Tablets and Capsules)

Syrups (Solutions, suspensions and emulsions)

Special Forms of tablets such as buccal tablets, sublingual tablets, orally disintegrating tablets

Thin films (for example Listerine pocketpaks)

Powders

Granules

Crystals

Natural or herbal products (such as seed, leaf or fruits)

Pastes (such as toothpastes)

Buccal films.

Ophthalmic Formulations:

These as the formulations meant to be administered in the eye. These include

Ophthalmic liquid solutions (such as eye drops, eye lotions, suspension, ointment, emulsion)

Inhalant Formulations:

The drug formulations intended to be administered via inhalation are included in this category. These include:

Aerosols

Inhalers

Nebulizers

Smoke

Vaporizers

Fumes

Parenteral Formulation:

Parenteral includes the dosage forms that are meant to be injected in the body. Various routes for parenteral administration include:

Intra dermal (ID)

Subcutaneous (SC)

Intra muscular (IM)

Intra osseous (IO)

Intra peritoneal (IP)

Intra venous (IV)

Intra thecal (IT)

Topical Formulations:

Drugs meant to be applied externally (on the skin) are known as topical preparations.

These include the following:

 Creams

Gels

Liniment

Balms

Lotions

Ointments

Ear drops (Price preparation)

Eye drops (Ophthalmic preparation)

Skin patches (transdermal preparation)

Vaginal rings

Dermal patch

Powder

Talc

Granules

Suppositories:

Suppositories are preparations that are administered through any body cavity other than the oral cavity. These include the following products:

Vaginal suppositories (for example douches and passaries)

Rectal suppositories

Urethral suppositories

Nasal suppositories.

References;

1.            Simler, R., Walsh, G., Mattaliano, R.J., Guziewicz, N., and Perez-Ramirez, B. (2008). Maximizing Data Collection and Analysis during Preformulation of Bio therapeutic Proteins. Bio Process International 6(10), 38-45.

2.            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.

3.            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