Nanoscale Surface Characterization and Miscibility Study of a Spray-Dried Injectable Polymeric Matrix Consisting of Poly(lactic-co-glycolic acid) and Polyvinylpyrrolidone

• Published in: Journal of pharmaceutical sciences 2012-09, Vol.101 (9), p.3473-3485
• Main Authors: Meeus, Joke, Chen, Xinyong, Scurr, David J., Ciarnelli, Valeria, Amssoms, Katie, Roberts, Clive J., Davies, Martyn C., Den Mooter, Guy van
• Format: Article
• Language: English
• Subjects: atomic force microscopy; Biological and medical sciences; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; controlled release; Delayed-Action Preparations; Drug Carriers; DSC; General pharmacology; Injections, Intramuscular; Injections, Subcutaneous; Lactic Acid - chemistry; Medical sciences; Microscopy, Atomic Force; Microscopy, Electron, Scanning; microspheres; Models, Chemical; Nanoparticles; Nanotechnology; nanothermal analysis; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - chemistry; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Photoelectron Spectroscopy; PLGA; Polyglycolic Acid - chemistry; Povidone - chemistry; PVP; Solubility; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; spray drying; Surface Properties; Technology, Pharmaceutical - methods; time-of-flight secondary ion mass spectrometry; Water - chemistry; X-ray photoelectron spectroscopy
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.23131

Injectable controlled-release formulations are of increasing interest for the treatment of chronic diseases. This study aims to develop and characterize a polymeric matrix for intramuscular or subcutaneous injection, consisting of two biocompatible polymers, particularly suitable for formulating poorly soluble drugs. For this matrix, the water-insoluble polymer poly(lactic-co-glycolic acid) (PLGA) is combined with the water-soluble polymer polyvinylpyrrolidone (PVP). Microparticles of these two polymers were prepared by spray drying. The phase behavior of the samples was studied by means of modulated differential scanning calorimetry and the results showed that phase separation occurred in the bulk sample through evidence of two mixed amorphous phases, namely, a PLGA-rich phase and a PVP-rich phase. Characterization of the samples by scanning electron microscopy demonstrated that the spray-dried particles were hollow with a thin shell. Because of the importance in relation to stability and drug release, information about the surface of the microparticles was collected by different complementary surface analysis techniques. Atomic force microscopy gathered information about the morphology and phase behavior of the microparticle surface. Time-of-flight secondary ion mass spectrometry analysis of the particles revealed that the surface consisted mainly of the PLGA-rich phase. This was confirmed by X-ray photoelectron spectroscopy at an increased sampling depth (∼10nm). Nanothermal analysis proved to be an innovative way to thermally detect the presence of the PLGA-dominated surface layer and the underlying PVP phase. Taken together, this information provides a rational basis for predicting the likely drug release behavior this formulation will display. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association.