title: Inventory of oral anticancer agents: Pharmaceutical formulation aspects with focus on the solid dispersion technique.
abstract: Dissolution from the pharmaceutical formulation is a prerequisite for complete and consistent absorption of any orally administered drug, including anticancer agents (oncolytics). Poor dissolution of an oncolytic can result in low oral bioavailability, high variability in blood concentrations and with that suboptimal or even failing therapy. This review discusses pharmaceutical formulation aspects and absorption pharmacokinetics of currently licensed orally administered oncolytics. In nearly half of orally dosed oncolytics poor dissolution is likely to play a major role in low and unpredictable absorption. Dissolution-limited drug absorption can be improved with a solid dispersion which is a formulation method that induces super-saturated drug dissolution and with that it enhances in vivo absorption. This review discusses formulation principles with focus on the solid dispersion technology and how it works to enhance drug absorption. There are currently three licensed orally dosed oncolytics formulated as a solid dispersion (everolimus, vemurafenib and regorafenib) and these formulations result in remarkably improved dissolution and absorption compared to what can be achieved with conventional formulations of the respective oncolytics. Because of the successful implementation of these three solid dispersion formulations, we encourage the application of this formulation method for poorly soluble oral oncolytics.
authors: Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/MC Slotervaart, Louwesweg 6, 1066 EC Amsterdam, The Netherlands. Electronic address: emilia.sawicki@gmail.com.
authors: E
authors: E
authors: Sawicki
authors: Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Science Faculty, Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmaco-epidemiology & Clinical Pharmacology, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors: J H M
authors: JH
authors: Schellens
authors: Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/MC Slotervaart, Louwesweg 6, 1066 EC Amsterdam, The Netherlands; Department of Clinical Pharmacology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands; Science Faculty, Utrecht Institute for Pharmaceutical Sciences (UIPS), Division of Pharmaco-epidemiology & Clinical Pharmacology, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors: J H
authors: JH
authors: Beijnen
authors: Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute/MC Slotervaart, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.
authors: B
authors: B
authors: Nuijen
mesh_terms: D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D004304:Dosage Forms; D000068338:Everolimus / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011725:Pyridines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D004304:Dosage Forms; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D013449:Sulfonamides; D000077484:Vemurafenib; C559147:regorafenib; D000068338:Everolimus
keywords: Bioavailability; Dissolution; Pharmacokinetics; Solid dispersion; Solubility; Variability