3D printed capsules for quantitative regional absorption studies in the GI tract

Area of Science:

• Pharmaceutical Sciences
• Additive Manufacturing
• Drug Delivery Systems

Background:

• Early drug development requires evaluating drug substance, product, and bioperformance.
• Assessing modified-release drug products in early clinical phases presents a significant challenge.
• Current oral drug product forms lack the ability to provide a wide range of controlled release profiles.

Purpose of the Study:

• To develop a 3D printing (3DP) strategy for creating polyvinyl alcohol (PVA) capsule shells with tunable drug release profiles.
• To demonstrate the control of drug release induction time by varying capsule wall thickness.
• To evaluate the in vitro and in vivo performance of 3D printed capsules for regional drug absorption studies.

Main Methods:

• Additive manufacturing (3D printing) was used to fabricate PVA capsule shells.
• Capsule wall thickness was systematically varied to control drug release induction time.
• Dissolution tests were performed using custom-designed 3D printed hanging baskets in a USP 2 apparatus.
• In vivo studies were conducted in beagle dogs to assess regional gastrointestinal absorption.

Main Results:

• A wide range of drug release induction times (12 to 198 minutes) was achieved by controlling capsule wall thickness.
• 3D printed capsules demonstrated a controllable delayed burst release profile.
• Initial analysis indicated a good in vitro/in vivo relationship (IVIVR).

Conclusions:

• 3D printing offers a novel and versatile platform for creating modified-release oral dosage forms.
• The ability to precisely control drug release induction times facilitates early-stage drug evaluation and regional absorption studies.
• This 3DP strategy provides a unique advantage over currently available commercial oral drug products.