Recent advances in lipid-based long-acting injectable depot formulations.

Long-acting injectable (LAIs) delivery systems sustain the drug therapeutic action in the body, resulting in reduced dosage regimen, toxicity, and improved patient compliance. Lipid-based depots are biocompatible, provide extended drug release, and improve drug stability, making them suitable for systemic and localized treatment of various chronic ailments, including psychosis, diabetes, hormonal disorders, arthritis, ocular diseases, and cancer. These depots include oil solutions, suspensions, oleogels, liquid crystalline systems, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, phospholipid phase separation gel, vesicular phospholipid gel etc. This review summarizes recent advancements in lipid-based LAIs for delivering small and macromolecules, and their potential in managing chronic diseases. It also provides an overview of the lipid depots available in market or clinical phase, as well as patents for lipid-based LAIs. Furthermore, this review critically discusses the current scenario of using in vitro release methods to establish IVIVC and highlights the challenges involved in developing lipid-based LAIs.

Analytical and Computational Methods for the Determination of Drug-Polymer Solubility and Miscibility.

In the pharmaceutical industry, poorly water-soluble drugs require enabling technologies to increase apparent solubility in the biological environment. Amorphous solid dispersion (ASD) has emerged as an attractive strategy that has been used to market more than 20 oral pharmaceutical products. The amorphous form is inherently unstable and exhibits phase separation and crystallization during shelf life storage. Polymers stabilize the amorphous drug by antiplasticization, reducing molecular mobility, reducing chemical potential of drug, and increasing glass transition temperature in ASD. Here, drug-polymer miscibility is an important contributor to the physical stability of ASDs. The current Review discusses the basics of drug-polymer interactions with the major focus on the methods for the evaluation of solubility and miscibility of the drug in the polymer. Methods for the evaluation of drug-polymer solubility and miscibility have been classified as thermal, spectroscopic, microscopic, solid-liquid equilibrium-based, rheological, and computational methods. Thermal methods have been commonly used to determine the solubility of the drug in the polymer, while other methods provide qualitative information about drug-polymer miscibility. Despite advancements, the majority of these methods are still inadequate to provide the value of drug-polymer miscibility at room temperature. There is still a need for methods that can accurately determine drug-polymer miscibility at pharmaceutically relevant temperatures.