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

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.

Conclusions
This study developed a series of novel, versatile, and straightforward controlled-release co-processed excipients assembled with nanoparticles and a direct compressed pharmaceutic excipient. The method proposed to prepare these co-processed excipients had different advantages, such as (i) easy to implement; (ii) solvent-free; (iii) possible industrial scaling-up; (iv) good rheological and compressibility properties; and (v) capability to form inert compacts that work as a release platform. The best Di-Tab®:SLN ratio was determined to be 2:0.6 for batch 3, which had good flow properties and the compatibility necessary to withstand the direct compression process. These co-processed systems could control the release rate for an extended time by an easy manufacturing process by direct compression. It was possible, as well, to develop a similar controlled-release system for ranitidine chloride—8 h—by modifying the compression force. Other means of controlling release—e.g., adding soluble fillers—are currently being studied. The behavior of the co-processed excipients fit the Higuchi model for matrix systems. In conclusion, this optimized co-processed excipient could provide a tool that will help resolve the lack of new, functional excipients for the pharmaceutics industry that are free of chemical changes and enhance the properties of the raw excipients.

Download the full article here: Evaluation-and-Comparison-of-Solid-Lipid-Nanoparticles-and-Nanostructured-Lipid-Carriers-as-Vectors-to-Develop-Hydrochlorothiazide-Effective-and-Safe-Pediatric-Oral-Liquid-Formulations

or continue reading here: Serrano-Mora, L.E.; Zambrano-Zaragoza, M.L.; Mendoza-Muñoz, N.; Leyva-Gómez, G.; Urbán-Morlán, Z.; Quintanar-Guerrero, D. Preparation of Co-Processed Excipients for Controlled-Release of Drugs Assembled with Solid Lipid Nanoparticles and Direct Compression Materials. Molecules 2021, 26, 2093. https://doi.org/10.3390/molecules26072093

Materials
The direct compression process of materials (dicalcium phosphate dihydrate, Di-Tab®; Innophonos) and the drug ranitidine hydrochloride (˃99%) were donated by HELM Mexico. Glyceryl behenate (Compritol® 888 ATO; Gattefossé) was purchased from Lyontec (Mexico City, Mexico). The stabilizing agent, Pluronic F-68®, was obtained from Aldrich (Merck Chemicals GmbH, Germany). Distilled water was of Milli-Q quality (Millipore, Bedford, MD, USA). All other reagents were of at least analytical grade.

What is Compritol® 888 ATO?

A glyceride with a high melting point used as a modified release agent or lubricant in tablets. Can also be used in lipid coating technologies and as lipid carrier for nanoparticles.

Main funtionalities
Modified release matrix former for tablet. Lubricant for tablet—independent of mixing time and speed. Lipid carrier former for solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC). Coating agent for taste masking and protection of sensitive APIs. Listed in the European STEP database for excipients in pediatric medicines. Safety of use is inferred by GRAS status and precedence of use in approved pharmaceutical products.

Main formulation technologies
Tablet compression (direct and wet granulation). Melt processes: granulation, extrusion, coating, prilling, spray congealing. Nanoparticle, nanocarrier formulation.