In vitro-in vivo correlation from lactide-co-glycolide polymeric dosage forms

Area of Science:

• Pharmacokinetics and Drug Delivery
• Biopharmaceutics
• Materials Science

Background:

• Long-acting injectable formulations are crucial for improving patient adherence in psychiatric treatment.
• Establishing in vitro-in vivo correlations (IVIVCs) is essential for predicting drug performance and ensuring formulation quality.
• Risperidone, an atypical antipsychotic, is available in long-acting subcutaneous formulations.

Purpose of the Study:

• To compare the in vitro drug release of four risperidone long-acting subcutaneous formulations with their in vivo performance.
• To establish a Level A in vitro-in vivo correlation (IVIVC) for these formulations.
• To evaluate the suitability of fractional AUC as a substitute for the Nelson-Wagner method in IVIVC analysis.

Main Methods:

• Four risperidone microsphere formulations were prepared using two different PLGA copolymers (50:50 and 75:25).
• In vitro drug release was assessed at 37°C using the modified dialysis technique.
• In vivo performance was evaluated using deconvolution (Nelson-Wagner method) and fractional AUC approaches.

Main Results:

• In vitro release profiles showed a rank order consistent with in vivo data, with 50:50 PLGA formulations releasing drug faster than 75:25 PLGA formulations.
• Both in vivo methods (deconvolution and fractional AUC) demonstrated the same rank order of drug release as observed in vitro.
• An excellent linear correlation (R² values 0.97-0.99) was achieved between in vitro release and in vivo performance, establishing a Level A IVIVC.

Conclusions:

• A Level A IVIVC was successfully established for risperidone long-acting subcutaneous formulations.
• The fractional AUC method can serve as a viable alternative to the FDA-recommended Nelson-Wagner deconvolution method.
• Appropriate selection of in vitro drug release methods is critical for developing reliable long-acting injectable formulations and achieving robust IVIVCs.