Preparation of Co-Processed Excipients for Controlled-Release of Drugs Assembled with Solid Lipid Nanoparticles and Direct Compression Materials

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-04, Vol.26 (7), p.2093
• Main Authors: Serrano-Mora, Luis Eduardo, Zambrano-Zaragoza, María L, Mendoza-Muñoz, Néstor, Leyva-Gómez, Gerardo, Urbán-Morlán, Zaida, Quintanar-Guerrero, David
• Format: Article
• Language: English
• Subjects: Calcium phosphates; co-processed excipient; Compressibility; Compression; Compressive Strength; Controlled release; Delayed-Action Preparations - pharmacology; dicalcium phosphate dihydrate; Drug delivery; Drug Liberation; Excipients; Excipients - chemistry; Lipids; Lipids - chemistry; Mechanical properties; Morphology; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Particle Size; Pharmaceutical industry; Pharmaceuticals; Polyvinyl alcohol; Powder; Powders; Ranitidine; Ranitidine - pharmacology; Ranitidine hydrochloride; Rheological properties; Rheology; solid lipid nanoparticles
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26072093

The purpose of the study was to develop a novel, directly compressible, co-processed excipient capable of providing a controlled-release drug system for the pharmaceutical industry. A co-processed powder was formed by adsorption of solid lipid nanoparticles (SLN) as a controlled-release film onto a functional excipient, in this case, dicalcium phosphate dihydrate (DPD), for direct compression (Di-Tab ). The co-processed excipient has advantages: easy to implement; solvent-free; industrial scaling-up; good rheological and compressibility properties; and the capability to form an inert platform. Six different batches of Di-Tab :SLN weight ratios were prepared (4:0.6, 3:0.6, 2:0.6, 1:0.6, 0.5:0.6, and 0.25:0.6). BCS class III ranitidine hydrochloride was selected as a drug model to evaluate the mixture's controlled-release capabilities. The co-processed excipients were characterized in terms of powder rheology and dissolution rate. The best Di-Tab :SLN ratio proved to be 2:0.6, as it showed high functionality with good flow and compressibility properties (Carr Index = 16 ± 1, Hausner Index = 1.19 ± 0.04). This ratio could control release for up to 8 h, so it fits the ideal profile calculated based on biopharmaceutical data. The compressed systems obtained using this powder mixture behave as a matrix platform in which Fickian diffusion governs the release. The Higuchi model can explain their behavior.