Solid Oral Dosage Form II

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Questions and Answers

What is the maximum acceptable drug loading (DL) percentage for formulations deemed promising for high speed manufacturing?

Greater than 5%

Less than 2% (correct)

Less than 1%

Between 2% and 5%

Which of the following components is classified as a lubricant in the provided formulation?

GLYCOLYS

Magnesium Sterate (correct)

Pharmacel PH-102

SuperTab 11SD

Which category of drug loading percentage corresponds to formulations that require excipient compactibility testing?

Between 2% and 5% (correct)

Less than 2%

Equal to 4%

Greater than 5%

What is the primary function of Ac-Di-Sol 711 in the formulations provided?

Superdisintegrant (B) Signup and view all the answers

Why is it essential to test for excipient compactibility in formulations?

To ascertain if the excipients proposed can function as backups. (A) Signup and view all the answers

What is the typical solid fraction (SF) aimed for during the initial trials of tablet compaction simulations?

0.85 (A) Signup and view all the answers

Which mechanical property is directly linked to a tablet's resistance to fracturing?

Tensile strength (D) Signup and view all the answers

Which option is NOT associated with tablet capping?

Increase in tablet density (A) Signup and view all the answers

In compaction simulations, applying larger compaction pressure may not necessarily affect which aspect of the tablet?

Solid fraction (SF) (D) Signup and view all the answers

What type of compaction simulator is typically used to predict compaction properties during tablet manufacturing?

Multi-station tablet press (D) Signup and view all the answers

What is one major advantage and one disadvantage of direct compression in tablet manufacturing?

Advantage: Direct compression is simple and economical. Disadvantage: It is sensitive to material properties, especially for high drug loadings. Signup and view all the answers

Why is drug loading (DL) important in the formulation development process?

Drug loading is critical as it affects the formulation design and can influence API content uniformity and mechanical properties of the tablets. Signup and view all the answers

How does drug loading less than 2% differ from drug loading greater than 5% in terms of formulation challenges?

Drug loading less than 2% primarily focuses on API content uniformity, while above 5% poses challenges related to final blend content uniformity and mechanical properties. Signup and view all the answers

What is the role of intrinsic API properties in the formulation of direct compression tablets?

Intrinsic API properties are essential as they determine how the material will behave during the compression process and affect the final tablet quality. Signup and view all the answers

Explain the significance of characterizing formulations during direct compression development.

Characterizing formulations helps identify reliable manufacturing processes and ensures that the final product meets quality and efficacy standards. Signup and view all the answers

Study Notes

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.

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Description

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.