title: Simplified formulations with high drug loads for continuous twin-screw granulation.
abstract: As different batches of the same excipients will be intermixed during continuous processes, the traceability of batches is complicated. Simplified formulations may help to reduce problems related to batch intermixing and traceability. Twin-screw granulation with subsequent tableting was used to produce granules and tablets, containing drug, disintegrant and binder (binary and ternary mixtures), only. Drug loads up to 90% were achieved and five different disintegrants were screened for keeping their disintegration suitability after wetting. Granule size distributions were consistently mono-modal and narrow. Granule strength reached higher values, using ternary mixtures. Tablets containing croscarmellose-Na as disintegrant displayed tensile strengths up to 3.1MPa and disintegration times from 400 to 466s, resulting in the most robust disintegrant. Dissolution was overall complete and above 96% within 30 min. Na-starch glycolate offers tensile strengths up to 2.8MPa at disintegration times from 25s to 1031s, providing the broadest application window, as it corresponds in some parts to different definitions of orodispersible tablets. Tablets containing micronized crospovidone are not suitable for immediate release, but showed possibilities to produce highly drug loaded, prolonged release tablets. Tablets and granules from simplified formulations offer great opportunities to improve continuous processes, present performances comparable to more complicated formulations and are able to correspond to requirements of the authorities.
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstr. 1, 40225 Duesseldorf, Germany. Electronic address: Robin.Meier@hhu.de.
authors.forename: R
authors.initials: R
authors.lastname: Meier
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstr. 1, 40225 Duesseldorf, Germany; Faculty of Bio- and Chemical Engineering, Technical University Dortmund, Emil-Figge-Str. 68, 44227 Dortmund, Germany. Electronic address: Markus.Thommes@bci.tu-dortmund.de.
authors.forename: M
authors.initials: M
authors.lastname: Thommes
authors.affiliation: Novartis AG, 4002 Basel, Switzerland. Electronic address: Norbert.Rasenack@novartis.com.
authors.forename: N
authors.initials: N
authors.lastname: Rasenack
authors.affiliation: Novartis AG, 4002 Basel, Switzerland. Electronic address: Markus.Krumme@novartis.com.
authors.forename: M
authors.initials: M
authors.lastname: Krumme
authors.affiliation: Novartis AG, 4002 Basel, Switzerland. Electronic address: Klaus-Peter.Moll@novartis.com.
authors.forename: K-P
authors.initials: KP
authors.lastname: Moll
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstr. 1, 40225 Duesseldorf, Germany. Electronic address: Kleinebudde@hhu.de.
authors.forename: P
authors.initials: P
authors.lastname: Kleinebudde
mesh_terms: D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013213:Starch / Q000031:analogs & derivatives / Q000737:chemistry; D013607:Tablets; D013718:Tensile Strength
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D013607:Tablets; D013213:Starch; C048390:sodium starch glycolate; D011205:Povidone; D002266:Carboxymethylcellulose Sodium; D007052:Ibuprofen
keywords: Continuous processes; Drug load; Granule and tablet quality; Simplified formulations; Twin-screw granulation