Solid Oral Dosage Form II

Course Information

• Course Name: PR5217 Formulation Science
• Module: L08 Solid Oral Dosage Form II
• Instructor: Dun Jiangnan, Ph.D.
• University: National University of Singapore
• Academic Year: AY24/25.S1
• Date: 17-OCT-2024

Learning Outcomes

• Understand general formulation development strategies in Direct Compression.
• Understand the role of different drug loadings in formulation development.
• Understand common characterizations in tablet formulation development.

Direct Compression (DC)

• Simplest manufacturing technology for tablets.
• Raw materials are mixed to form a blend, then compressed to form a tablet.
• Pros: Simple, Economical
• Cons: Sensitive to material properties, Risky for high drug loading, Risky for high potency drug formulation

Goals of Formulation Development in DC

• Identify formulation composition.
• Identify a suitable manufacturing process.
• Limited amount of API in early development (minimize the use of API).
• Minimized formulation development time.
• Prioritize direct compression.
• Identify reliable lab-scale manufacturing process that can be scaled robustly to clinical supply.

Drug Loading (DL)

• Drug loading (dose strength) is crucial in formulation design.
• DL is categorized as: Less than 2%, Between 2% to 5%, Larger than 5%.

DL < 2%

• Typically seen in high-potency drugs.
• Extremely low blood concentration is needed for therapeutic effect without unexpected toxicity.
• High risk of API content uniformity resulting in high risk of toxicity in specific batches.
• Not suitable for direct compression.

DL between 2% to 5%

• Mechanical properties are dominated by excipients.
• Mechanical properties are characterized via compaction simulation.
• Employing "platform formulations", using common excipient ratios (e.g., 60% MCC, 40% LM) for formulation consistency.
• Evaluating excipient compatibility through multiple formulation trials.
• Compaction simulation to identify ideal solid fraction (SF) (typically around 0.85) for manufacturability and tablet properties.
• Mechanical properties of interest: Tensile strength, Hardness, Friability, Breaking force.
• Capping and lamination are common tablet defects (related to ejection or handling flaws).

DL > 5%

• Main challenge is mechanical properties and manufacturability.
• Maximum possible DL needs identification, to ensure suitable for direct compression.
• Measuring flowability of API and final blends to find DL threshold.
• Employing methods like Ring Shear Cell Tests and Wall Friction Tests to determine the required DL.
• Using dilution to reach a suitable DL, otherwise using a completely new formulation.
• Prototype selection is done by varying API and total tablet weight to determine suitable mechanical properties.

Dissolution Enhancement

• Formulation strategies like amorphous solid dispersion, replacing hydrophobic excipients with hydrophilic ones.
• Decreasing particle size of drug substance and including surfactants in the formulation (e.g., PVP coatings).
• Surface wettability enhances tablet dissolution.

Surface Wetting

• The contact angle is formed when a solid contacts a liquid.
• Factors like surface morphology, chemical composition, and intermolecular forces influence wetting.

Punch Sticking

• Adherence of powder material to the tooling surface during compaction.
• Punch sticking is usually spotted late during the formulation design.
• Poor physicochemical and mechanical properties are causes for sticking.
• Several sticking types exist: mild, severe (could include tablet picking).

Further Notes

• Non-linear dose design and Linear dose design (preferred) for prototypes are suitable design approaches for appropriate drug loading ranges.

Test your knowledge on various aspects of pharmaceutical formulations, including drug loading percentages, excipient compactibility, and mechanical properties of tablets. This quiz covers essential concepts in tablet compaction simulations and formulation components. Ideal for students and professionals in pharmaceutical sciences.