Definition
Excipients are substances other than an active pharmaceutical ingredient (API) used to make a formulated drug or medicine.
Excipients are an essential and integral part of medicine. They are often referred to as the so-called “inactive” or “inert” ingredients in a product, but they can exert indirect and direct physiological effects which are additional to the required action of the API.
The International Pharmaceutical Excipients Council Federation, which defines excipients as:
substances, other than the active drug substance of finished dosage form, which have been appropriately evaluated for safety and are included in a drug delivery system to either aid the processing of the drug delivery system during its manufacture; protect; support; enhance stability, bioavailability, or patient acceptability; assist in product identification, or enhance any other attributes of the overall safety and effectiveness of the drug delivery system during storage or use.
This is a comprehensive definition of excipients. The US Pharmacopeia National Formulary (USP–NF) states that ‘excipients are components of a finished drug product other than the API and are added during formulation for a specific purpose’.
Classification
In the early days of medicine, excipients were chosen from materials already used for food and hence known to have the desired degree of safety and stability. Thus wine, vinegar and honey were used as solvents or vehicles for oral administration and olive oil, suet and lard for application to the skin. Like the drugs themselves, some excipients such as acacia and tragacanth show the early influence of the Mediterranean countries on pharmacy and medicine. Thus, until comparatively recent times, both drugs and excipients were of natural origin, but a situation is now developing in which the synthetic excipient is almost as common as the synthetic drug.
Many synthetic drugs are highly reactive in the chemical sense and are sensitive to oxidation, pH changes, moisture, etc., to such a degree that formulations frequently must provide a specific stabilizer or preservative. Thus, in addition to extending the range of antibacterial and antifungal agents, modern excipients include chelating agents, antioxidants and other “chemical” stabilizers.
The USP–NF classifies excipients according to their function to:
1- Pharmacokinetic purposes:
- Disintegrants
- Sustained-release agents
- Coatings:
a) Enteric
b) Film
c) Sugar
2- Mechanical & Technological purposes:
- Lubricants
- Glidants
- Binders
- Fillers
- Print inks
3- Drug stability purposes:
- Preservatives
- Stabilizers:
a) Antioxidant
b) chelating agent
c) buffering agents
4- Aesthetic purposes:
- Colorants, Flavors & Sweetening agents
- Bitterness removing agents
- Viscosity imparting agents
5- Aqueous solubility enhancers:
- Alkalinizing agents
- Acidifiers
6- Synergistic therapeutic purposes:
As liquid vehicle anti-microbial & sweetening agents
however, most excipients are multifunctional and their performance in a specific application may depend on the process and formulation.
in the United States Pharmacopoeia (USP) chapter (1078) on good manufacturing practices for bulk pharmaceutical excipients, excipients may be included in the formulation to:
- aid in the processing of the drug delivery system during its manufacture,
- protect, support or enhance stability, bioavailability or patient acceptability,
- assist in product identification,
- enhance any other attribute of the overall safety, effectiveness or delivery of the drug during storage or use.
The selection of excipients is one of the pharmacist’s more important responsibilities. The use of excipients depends on the type of dosage form. For example, oral solid dosage forms, such as tablets, need diluents (fillers, bulking agents), disintegrants, binders, lubricants, and glidants. liquid dosage forms, such as solutions or suspension, do not need disintegrants, coatings, lubricants, glidants, or binders, but require solvents and/or co-solvents, buffering agents, preservatives, antioxidants, wetting agents, antifoaming agents, suspending agents, sweetening agents, or flavouring agents. There are several dozens of dosage forms based on the physical properties or route of administrations. Various dosage forms also exist for a particular API or drug.
Dosage Forms
A dosage form is a physical form of a final pharmaceutical preparation based on therapeutic intention, route of administration, and dosing.
Most APIs are in solid form, possibly crystalline or powder. We need small amounts of APIs, usually in the range of 5–500 mg, every time medicine is made. There are even drugs that need less than 1 mg of an API.
We need dosage forms to ensure patients take the right amount of a drug in the correct form, depending on the requirements of the patient. For example, a patient in the emergency room of a hospital needs a drug immediately but is unable to take medicine orally. The parenteral (injectable) form is appropriate as it acts quickly. Some children cannot swallow pills, so they are given liquid dosage forms or chewable candy forms. There are dozens of reasons for having various dosage forms
Reasons for having different dosage forms:
- Inhalation therapy
- Topical use
- Extended drug action
- Quick drug action option
- Easy identification of drug
- Masking bad taste
- Variety of dosage forms
- Convenient delivery
- Delivery of accurate amount
- Delivery of very small amount of drug (<1 mg)
- Safe delivery
- Stable undegraded drug
- Protection from environment
- Liquid dosage form for easy administration
- No destruction from gastric acid
The most common, convenient, and cheapest dosage form is the tablet form, which requires a number of excipients. Fewer excipients are used in injectable dosage forms. When making tablets, the oral solid dosage form, the objective is to have a balanced formulation, so it undergoes immediate disintegration in the gastrointestinal tract (GIT). The primary objective of a drug therapy is to introduce the drug or API in an exact therapeutic dose (amount) at regular intervals, considering the patient’s compliance.
Before talking about dosage form formulation, we should know more about excipients classification and its’ ingredients.
Resources:
- An Introduction to Pharmaceutical Formulation by A. G. Fishburn, W. H. Linnell and A. J. Evans.
- An introduction to pharmaceutical sciences Production, chemistry, techniques and technology by Jiben Roy.
- Pharmaceutical Formulation, The Science and Technology of Dosage Forms, Geoffrey D. Tovey
- Excipients: Kano Analysis and Quality by Design, BRIAN A. C. CARLIN AND C. G. WILSON
- AQs, What Are Pharmaceutical Excipients? http://www.ipecamericas.org/what-ipec-americas/faqs#question1.
- U.S. Pharmacopoeia-National Formulary [USP 40 NF 35], United states Pharmacopeial Convention, Inc., rockville, Md, USA, 2017.
