Microcrystalline cellulose, a direct compression binder in a quality by design environment--a review.

The ICH quality vision introduced the concept of quality by design (QbD), which requires a greater understanding of the raw material attributes, of process parameters, of their variability and their interactions. Microcrystalline cellulose (MCC) is one of the most important tableting excipients thanks to its outstanding dry binding properties, enabling the manufacture of tablets by direct compression (DC). DC remains the most economical technique to produce large batches of tablets, however its efficacy is directly impacted by the raw material attributes. Therefore excipients' variability and their impact on drug product performance need to be thoroughly understood. To help with this process, this review article gathers prior knowledge on MCC, focuses on its use in DC and lists some of its potential critical material attributes (CMAs).

Simulated food effects on drug release from ethylcellulose: PVA-PEG graft copolymer-coated pellets.

BACKGROUND: Food effects might substantially alter drug release from oral controlled release dosage forms in vivo. METHODS: The robustness of a novel type of controlled release film coating was investigated using various types of release media and two types of release apparatii. RESULTS: Importantly, none of the investigated conditions had a noteworthy impact on the release of freely water-soluble diltiazem HCl or slightly water-soluble theophylline from pellets coated with ethylcellulose containing small amounts of PVA-PEG graft copolymer. In particular, the presence of significant amounts of fats, carbohydrates, surfactants, bile salts, and calcium ions in the release medium did not alter drug release. Furthermore, changes in the pH and differences in the mechanical stress the dosage forms were exposed to did not affect drug release from the pellets. CONCLUSION: The investigated film coatings allowing for oral controlled drug delivery are highly robust in vitro and likely to be poorly sensitive to classical food effects in vivo.

Drug release mechanisms from ethylcellulose: PVA-PEG graft copolymer-coated pellets.

The aim of this study was to better understand the underlying drug release mechanisms from aqueous ethylcellulose-coated pellets containing different types of drugs and starter cores. Theophylline, paracetamol, metoprolol succinate, diltiazem HCl and metoprolol tartrate were used as model drugs exhibiting significantly different solubilities (e.g. 14, 19, 284, 662 and 800 mg/mL at 37 degrees C in 0.1N HCl). The pellet core consisted of a drug matrix, drug-layered sugar bead or drug-layered microcrystalline cellulose (MCC) bead, generating different osmotic driving forces upon contact with aqueous media. Importantly, the addition of small amounts of poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer (PVA-PEG graft copolymer) to the ethylcellulose coatings allowed for controlled drug release within 8-12h, irrespective of the type of drug and composition of the pellet core. Drug release was found to be controlled by diffusion through the intact polymeric membranes, irrespective of the drug solubility and type of core formulation. The ethylcellulose coating was dominant for the control of drug release, minimizing potential effects of the type of pellet core and nature of the surrounding bulk fluid, e.g. osmolality. Thus, this type of controlled drug delivery system can be used for very different drugs and is robust.