The main component of a drug product is the active pharmaceutical ingredient (API) but a finished drug product contains ingredients other than API. They are called excipients. Generally, they are compounds that are physically and chemically inert and are used for various reasons. Let’s get to know more about the pharmaceutical excipients in this article.
What Are Pharmaceutical Excipients?
Pharmaceutical excipients are substances that are added along with the active pharmaceutical ingredient in a finished drug product. In other words, everything other than the active ingredient in a finished drug formulation. They are usually chemically inert substances, meaning they have no therapeutic effect.
These are frequently used as lubricants, diluent, binders, flavorings, coating and coloring agents for the formulation.
Ideal Properties Of Excipients
Must be pharmacologically inert
Should not have any interaction with the drug
It must be cost effective
It should be stable, non-toxic and commercially available in the countries where the product is to be manufactured.
Pleasing organoleptic properties
Must be functional for the intended use
Classification Of Excipients
Excipients are classified according to their origin, route of administration and by functionality of the excipients in the drug product. Classification of excipients is given below:
Pharmaceutical Excipients Types:
Excipients are used in almost all drug products. Most commonly used pharmaceutical excipients are as follows: -
Binders: As the name suggests, they are used to bind or to adhere the molecules of a formulation. It provides mechanical strength to the tablet or granules and provides integrity to the final product. E.g. Starch, Gelatin, Acacia
Disintegrating/Super Disintegrating Agents: They are added to a tablet to facilitate the breaking or disintegration of the formulation for its absorption and action. E.g. Croscarmellose Sodium, Crospovidone
Diluents: Used to increase the bulk of the tablet or capsules when the drug dosage is insufficient for the tablet to reach the required size or weight. E.g. Microcrystalline Cellulose, Lactose Monohydrate, Calcium Phosphate Dehydrate
Glidants: Glidants are added to increase the flow property of the granules or powder materials and to decrease the friction between them. E.g. Colloidal Silicon Dioxide
Lubricants: They are useful in preventing the adhesion of tablet materials to the dies and punches surface, decrease the friction between the particles and may increase flow property. E.g. Magnesium Stearate, Talc, Silica
Coloring and Flavoring Agents: Coloring agents are used to add color to the formulation and flavoring agents are used to mask the unpleasant taste of the drug product. E.g. Dyes and Pigments (Coloring Agents), Peppermint Oil, Spearmint Oil (Flavoring Agent)
Regulatory Requirements For Pharmaceutical Excipients
Regulators set forward many conditions that must be satisfied to incorporate the excipients into the pharmaceutical product.
Safety, Toxicity and Precedence of use issues: The guideline issued by the European Commission in support of Directive 2011/62/EC states that “quality risk management principles should be used to assess the risks presented to the quality, safety and function of each excipient and to classify the excipient in question, e.g., as low risk, medium risk or high risk.”
Excipients have precedence of use in countries. For e.g., In The US, precedence of use is listed in the FDA Inactive Ingredient Database. The excipient manufacturers must first assess for precedence of use in countries where it is intended to be marketed.
GMP Requirements: Excipient manufacturers must strictly follow the GMP standards and requirements.
Compendial Requirements: Where included in pharmacopoeia, the excipient must be in compliance with the monograph requirements and also the general notices. Multiple compendia are used across the world out of which the most referenced are the:
USP-NF (United States Pharmacopeia - National Formulary)
Ph. Eur. (European Pharmacopoeia)
ChP (Chinese Pharmacopoeia)
JP (Japanese Pharmacopoeia)
JPE (Japanese Pharmaceutical Excipients)
Desired properties for marketed use: Excipient suppliers will have a range of data describing the functionality of the material if it has been used in other applications. This serves as valuable information for the excipient users while describing the functionality and the safety profile of the excipients.
Excipient Master Files and Other Filings: Excipient DMFs, CEP, Chinese Excipients Dossier, etc. are submitted to the relative regulatory authorities to provide confidential information regarding the excipient’s safety and compliance with appropriate GMP requirements.
ICH Guidelines: These guidelines are applicable to drug substances and medicinal products but are not directly applicable to excipients. Nonetheless, some elements of the ICH guideline provide guidance for topics relating to excipients, such as the GMP requirements.
Specific Safety Issues: The quality and origin of the excipients will have an impact on patient safety and religious purity. Therefore, the excipient suppliers must be knowledgeable and should have control over the origin of raw materials, degradation products of the excipients, elemental purities, residual solvents, additives and processing aids aspects of their processes.
Moreover, the excipient manufacturers must evaluate whether the materials can be suitably produced for intended marketed use.
Safety Considerations For Excipients In Pharmaceuticals
Initially excipients were considered safe as they were thought to be chemically inert but with sulfanilamide tragedy this was reversed. There is no general approval process for excipients, but it is approved together with a drug as a drug product.
Excipients can also have toxic effects; it must be limited to minimal amounts, as much as possible. Safety data of the excipients will be available except for novel excipients. Studies must be done on the safety of novel excipients, and the data must be provided as and when required by the health authority.
Adverse effects can occur not only due to active ingredients but also due to excipients used in the drug product. This must be noted and kept in mind to avoid drug products containing these excipients.
Since the quality of the excipients has a direct impact on the drug product, GMP requirements must be followed. The quantity of excipients plays a role in age, especially in premature infants and children due to their developing organs. Risk benefit assessment must be conducted for novel excipients so as to establish safety limits.
Challenges In The Development Of Pharmaceutical Excipient
The lack of harmonized standards and requirements for assessing the safety can delay the process of drug development and approval. Time and cost for developing new excipients is another challenge. As of now there is no specific approval process for excipients and if a finished drug product fails to get approval, automatically the excipient is also denied the approval.
With proper planning and expertise overcoming these challenges can be easily achieved. Artixio Consulting consists of a team of members with knowledge and years of expertise and can provide you with all the support that we can. Find out more about us by connecting us through info@artixio.com
FAQs On Excipients
1. Why are excipients crucial in formulations?
Excipients are added to the formulations to help in the manufacturing process, administration and also improving the delivery of the medicine. Excipients are used accordingly based on their functionality. E.g. Flavoring agents are added to mask the bitter taste of the drug.
2. Are pharmaceutical excipients safe for consumption?
Yes, excipients are often therapeutically inert substances. However, they are evaluated for their safety followed by regulatory approval. The number and the amount of excipient must be limited in pediatric drug products as their organs are still developing.
3. What is the role of excipients in controlled-release formulations?
They allow control of the rate of release of drug, transfer of API to particular sites, increase drug bioavailability and decrease side effects.
4. Can excipients interact with active pharmaceutical ingredients (APIs)?
Yes, interaction of excipients with API can occur. This can affect the stability, bioavailability and ultimately affect the efficacy of the drug product. Excipient - excipient interaction is also possible.
5. What are the latest innovations in pharmaceutical excipients?
Recent advancements include co-processed excipients, 3D printing, smart excipients that respond to specific stimuli, and functional excipients are some of the latest innovations.
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