Multiparticulates - Modern Oral Drug Products for our Society - Part 2
In January I shared the first article on multiparticulates with you. Here comes the second one with focus on "Optimized Drug Release – Optimizing the Solubility and Bioavailability of Poorly Soluble Drugs with Appropriate Multiparticulate Core Technology Platforms". Enjoy reading the publication by Norbert P?llinger from Glatt Pharmaceutical Services as in Pharm. Ind. 85, Nr. 2, 187–197 (2023). You can download both parts directly here.
Optimized Drug Release – Optimizing the Solubility and Bioavailability of Poorly Soluble Drugs with Appropriate Multiparticulate Core Technology Platforms
Many pharmaceutical drug compounds are poorly water-soluble or almost insoluble in water. Drug solubility is one of the most important parameters to achieve therapeutic concentration. Nowadays around 70 % of newly discovered drug candidates and approximately 40 % of marketed oral drugs are categorized as practically insoluble. Suitable technical operations in order to ensure adequate solubility and bioavailability can provide multiparticulates with their particular advantages.
4.1. Microenvironmental pH Modulation
Microenvironmental pH modulation is required for many basic drugs, with the aid of weak acids such as tartaric acid (fig. 12). Due to the high hygroscopicity of weak acids, the probability of degradation of the drug candidate by hydrolysis is very high when the drug is mixed with weak acids as an admixture, e.g. in matrix
tablets. Layer separation between acid and drug is recommended therefore to achieve long term stability of the product.
In Pradaxa pellets filled into capsules, tartaric acid ensures the bioavailability of Dabigatran. Tartaric acid creates a microenvironment required for the dissolution of the API and, hence, for the absorption thereof. A Dabigatran formulation without tartaric acid, when co-administered with a PPI, leads to a fall in bioavailability by 60–70 %; this could render the drug ineffective.
4.2. Amorphous Solid Dispersions
A common approach to improve the solubility of poorly water-soluble compounds is to formulate them as amorphous solid dispersions (ASD) with suitable polymer candidates. Hot-melt extrusion may not be feasible for thermosensitive compounds. Continue reading here
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Webinar Series on Multiparticulates
I would also suggest the following webinar series on multiparticulates. The series shares great content for anybody interested in the topic.
Multiparticulates 1?–?A modern Oral Drug Products for our Society
Multiparticulates 2?-?Multiparticulates from matrix core pellets – Glatt MicroPx and ProCell Technology
Multiparticulates 3?-?Multiparticulates from maxtrix core pellets – Glatt CPS
Multiparticulates 4a?-?Functional coating applications – The Basics
Multiparticulates 4b?-?Glatt Fluidbed Wurster Drug Layering and Coating - the Process
Multiparticulates 5?-?Product and process development applying QbD (quality by design) and DoE (design of experiments) concepts to define DS (design space)
Multiparticulates 6?-?DoE case studies in QbD development
Multiparticulates 7?-?Next Generation ODTS with high dosed Multiparticulates
Multiparticulates 8?-?Scale up considerations on the Wurster (bottomspray) fluidized bed process
Multiparticulates 9?-?Pellets from fluid bed processes – a smart concept for high(er) potent drug processing
Multiparticulates 10?-?Functional Tartaric Acid Pellets in Modern Formulation Challenges