Surface Characteristics of Spray-Dried Microspheres Consisting of PLGA and PVP: Relating the Influence of Heat and Humidity to the Thermal Characteristics of These Polymers

Abstract

In view of the increasing interest in injectable controlled release formulations for the treatment of chronic diseases, injectable polymeric microspheres consisting of a surface layer of poly(lactic-co-glycolic acid) (PLGA) and an underlying polyvinylpyrrolidone (PVP) layer were previously developed. The present study focuses on the influence of heat and humidity on the surface characteristics of these spray-dried PLGA/PVP microspheres. The response of the polymeric matrix to these factors will provide an insight into the expected release behavior and stability of the formulation. This should result in the development of a drug matrix with desired and tunable characteristics in terms of physicochemical stability and drug release profile, relevant in a later stage of research. Glass transition temperatures (Tgs) and miscibility behavior were analyzed by modulated differential scanning calorimetry (MDSC). Scanning electron microscopy (SEM) provided insight in particle morphology. Atomic force microscopy (AFM) was used to study the nanoscale topography and phase behavior of the samples. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) were utilized for surface chemical analysis and quantification respectively. It could be concluded that the surface characteristics (chemical composition, phase behavior, and topography) of spray-dried PVP/PLGA microparticles were affected by exposure to heat and humidity. When exposed to these conditions, a surface rearrangement occurs whereby an increase of PVP at the surface is observed, coupled with a decrease in PLGA. This phenomenon can be explained based upon the relative thermal characteristics and consequent molecular mobility of the two polymers.

Combination of (M)DSC and Surface Analysis to Study the Phase Behaviour and Drug Distribution of Ternary Solid Dispersions

“…The spatial distribution of the API and PLGA at the sample surface is represented in Figure 4. There is a negligible amount of PVP observed at the particle surface which is consistent with previous studies (8,9) and depicted in Figure 2 of the Supplementary Information. At the micron-scale resolution of the ToF-SIMS data the drug seems to be homogeneously distributed at the surface of the three model formulations.…”

“…In addition, the absence of a T g around 56°C (T g of the API) indicates that the API is molecularly dispersed in a phase separated system made up of a PLGA-rich phase and a PVP-rich phase. Preceding work has already revealed that hollow spheres are formed when PLGA and PVP are spray-dried together with a PLGA surface layer and an underlying PVP layer (8,9). The presence of PLGA at the particle surface is due to its surface activity and a consequence of restructuring of the methyl side groups of PLGA towards the droplet-air surface (8,19).…”

“…We have previously reported on the development of spray-dried polymeric microspheres for intramuscular injection for the long-term prophylaxis of infection with human immunodeficiency virus (HIV) (8,9). These shell structured microspheres contain two biocompatible polymers, poly(lactic-co-glycolic acid) (PLGA) and polyvinylpyrrolidone (PVP) and are made up of a PLGA-rich surface layer and an underlying PVP-rich phase (8).…”

“…MDSC analysis revealed, based upon the Gordon-Taylor equation, that the polymeric microspheres are estimated to consist of a PLGA-rich surface phase (85% PLGA, 15% PVP) and a PVP-rich underlying phase (97% PVP, 3% PLGA) (9).…”

“…The model drug used was an HIV protease inhibitor. The main contribution of AFM for the analysis of solid dispersions lies in its potential to spatially resolve the phase separation at nanoscale resolution (9,(13)(14)(15)(16) This study aims to clarify drug distribution in a multi-phased polymeric system. To do so, for the first time, (M)DSC was combined with ToF-SIMS and AFM to characterize the phase behaviour of ternary solid dispersions.…”