Pharmaceutical Excipients 2024-2025 powerpoint slides

Excipients in Drug Products
- Make up a significant portion of a drug product.
- Example: In a tablet containing 5mg of active pharmaceutical ingredient (API), a large portion of the tablet consists of excipients.
Role of Excipients
- Often referred to as inactive ingredients, they are crucial for the drug's delivery system and play a key role in efficacy.
- A well-designed formulation optimizes the therapeutic impact of the API by ensuring proper delivery.
- Key factors of delivery include timing, location, and amount.

Characteristics of Excipients
- Must be feasible and not interact with the active drug pharmacologically.
- Should be inert, stable, and cost-effective.
- Must remain effective for handling and maintaining product integrity.

Desired Characteristics
- Stability and Reproducibility: Ensure formulations are consistent.
- No Unwanted Interactions: Excipients must not interact negatively with the drug.
- Pharmacologically Inert: Should not exert any pharmacological effects.
- Functionality: Must provide desired functionality to the formulation.
- Cost-Effective: Should be budget-friendly for manufacturing.

Dosage Forms Examples:
- Tablets, coated hard capsules, oral strips, granules, syrups.
- Specific examples include XYLOC 1% tablets and bacteriostatic sodium chloride USP 0.9%.
- Diluents like sodium chloride must be carefully handled, potentially as single-dose solutions.

Impact of Poorly Designed Formulations
- May mask the effectiveness of the API.
- Formulation is often overlooked, especially during late development stages, reducing the chance for optimal synergy between formulation and API.
- Excipients should do more than just serve as transportation from manufacturer to patient.

Selection of Excipients
- Essential for creating stable and effective solid dosage forms.
- Facilitate administration and ensure consistent drug release and bioavailability.
- Protect the drug from degradation during storage and use.

FDA Guidelines
- Under 21CFR 330.1(e), OTC drugs must only use suitable inactive ingredients that are safe and do not interfere with the drug’s effectiveness.
- Ensure compliance with standards of identity, strength, quality, and purity.
- Additional resources: “FDA – Guidance for safety evaluation of excipients” available on Moodle.

Summary of Excipients' Functions
1. Ensure preparation has an appropriate shape and size for usability.
2. Optimize adsorption of active substances.
3. Ensure acceptable shelf life.
4. Prevent unpleasant taste or odor.
5. Facilitate easy production.

Different Functions
- Excipients protect, support, and enhance drug delivery.
- Assist in maintaining drug effectiveness and bioavailability.
- Play various roles including identification, stability enhancement, and overall safety during storage and use.

Influencing Factors
- The bioavailability of drugs is affected by formulation and production factors.
Categorization
- Excipient Factors
- Final Dosage Form (discussed in later lectures).

Evolving Views on Excipients
- Previously considered inert with no therapeutic action.
- Now recognized as influential in the rate and extent of drug absorption.
Key Excipients
- Diluents, surfactants, lubricants, disintegrants, viscosity-enhancing agents.

Diluents Overview
- Typically the most abundant excipients in formulations.
- Traditionally seen as inert materials that bulk up formulations.
- Play a role in drug release despite being chemically inert.

Effect of Diluents
- Changes in diluent can significantly impact bioavailability and toxicity.
- Case example: Use of sodium phenytoin in epilepsy treatment shows how a diluent change led to intoxication despite unchanged API quantity.

Comparison of Diluents
- Old formulation utilized calcium sulfate dihydrate, which hindered GI absorption of phenytoin.
- New formulation replaced it with lactose, leading to increased bioavailability and associated toxicity.

History of Surfactants
- Known for improving drug solubility.
- Not all surfactants are inert; their effects vary significantly on drug absorption.

Surfactant Effects
- Surfactant monomers may disrupt biological membranes, enhancing drug penetration and GI barrier absorption.
- Can cause toxic side effects or inhibit absorption due to micelle formation.

Mechanism of Action
- Surfactants can increase the release of poorly soluble drugs from formulations.
- They reduce solid/liquid interfacial tension, improving GI fluid penetration and resulting in faster dissolution and absorption rates.

Surfactant Applications
- Serve multiple roles: emulsifying agents, solubilizing agents, suspension stabilizers, and wetting agents in formulations.