Biopolymeric microparticles have been widely used for long-term release formulations of short half-life chemicals or synthetic peptides. Characterization of the drug release from microparticles is important to ensure product quality and desired pharmacological effect. However, there is no official method for long-term release parenteral dosage forms. Much work has been done to develop methods for in vitro drug release testing, generally grouped into three major categories: sample and separate, dialysis membrane, and continuous flow (flow-through cell) methods. In vitro drug release testing also plays an important role in providing insight into the in vivo performance of a product. In vitro release test with in vivo relevance can reduce the cost of conducting in vivo studies and accelerate drug product development. Therefore, investigation of the in vitro–in vivo correlation (IVIVC) is increasingly becoming an essential part of particulate formulation development. This review summarizes the principles of the in vitro release testing methods of biopolymeric particulate system with the recent research articles and discusses their characteristics including IVIVC, accelerated release testing methods, and stability of encapsulated drugs.

Recently, two oral-administered peptide pharmaceuticals, semaglutide and octreotide, have been developed and are considered as a breakthrough in peptide and protein drug delivery system development. In 2019, the Food and Drug Administration (FDA) approved an oral dosage form of semaglutide developed by Novo Nordisk (Rybelsus^®) for the treatment of type 2 diabetes. Subsequently, the octreotide capsule (Mycapssa^®), developed through Chiasma’s Transient Permeation Enhancer (TPE) technology, also received FDA approval in 2020 for the treatment of acromegaly. These two oral peptide products have been a significant success; however, a major obstacle to their oral delivery remains the poor permeability of peptides through the intestinal epithelium. Therefore, gastrointestinal permeation enhancers are of great relevance for the development of subsequent oral peptide products. Sodium salcaprozate (SNAC) and sodium caprylate (C8) have been used as gastrointestinal permeation enhancers for semaglutide and octreotide, respectively. Herein, we briefly review two approved products, Rybelsus^® and Mycapssa^®, and discuss the permeation properties of SNAC and medium chain fatty acids, sodium caprate (C10) and C8, focusing on Eligen technology using SNAC, TPE technology using C8, and gastrointestinal permeation enhancement technology (GIPET) using C10.

Nano differential scanning fluorimetry (nanoDSF) is a high-throughput protein stability screening technique that simultaneously monitors protein unfolding and aggregation properties. The thermal stability of immunoglobulin G (IgG) was investigated in three different buffers (sodium acetate, sodium citrate, and sodium phosphate) ranging from pH 4 to 8. In all three buffers, the midpoint temperature of thermal unfolding (T_m) showed a tendency to increase as the pH increased, but the aggregation propensity was different depending on the buffer species. The best stability against aggregation was obtained in the sodium acetate buffers below pH 4.6. On the other hand, IgG in the sodium citrate buffer had higher aggregation and viscosity than in the sodium acetate buffer at the same pH. Difference of aggregation between acetate and citrate buffers at the same pH could be explained by a protein–protein interaction study, performed with dynamic light scattering, which suggested that intermolecular interaction is attractive in citrate buffer but repulsive in acetate buffer. In conclusion, this study indicates that the sodium acetate buffer at pH 4.6 is suitable for IgG formulation, and the nanoDSF method is a powerful tool for thermal stability screening and optimal buffer selection in antibody formulations.

Because of its greater binding affinity and longer half-life than native glucagon-like peptide-1 (GLP-1), the GLP-1 receptor agonist lixisenatide is commonly used to treat type 2 diabetes mellitus. This study aimed to establish a simple and robust liquid chromatography–tandem mass spectrometry (LC–MS/MS) approach for lixisenatide for in vivo pharmacokinetic investigation. Methanol-based protein precipitation with formic acid was exploited for plasma sample extraction, using esomeprazole as the internal standard. Gradient elution with 0.1% formic acid in distilled water and acetonitrile was utilized for chromatographic separation. Mass spectrometry was used to monitor the MRM transition at m/z 810.8 → 129.2 for lixisenatide. In rat plasma, lixisenatide had a lower limit of quantification of 10 ng/mL. The LC–MS/MS was applied to describe the pharmacokinetics of lixisenatide in rats following intravenous and subcutaneous dosing. The average half-life of lixisenatide was 0.37 ± 0.06 h after intravenous injection. The estimated subcutaneous bioavailability of lixisenatide was 2.17%. This LC–MS/MS analysis might be relevant in future research to create novel dosage formulations of lixisenatide and other GLP-1 receptor agonists with optimal therapeutic effectiveness.