Development of a Level A in Vitro-in Vivo Correlation for Veliparib (ABT-888) Extended Release Tablet Formulation

• Published in: Pharmaceutical research Vol. 34; no. 6; pp. 1187 - 1192
• Main Authors: Mittapalli, Rajendar K., Nuthalapati, Silpa, Delke DeBord, Alyssa E., Xiong, Hao
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2017; Springer; Springer Nature B.V
• Subjects: Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Area Under Curve; Benzimidazoles - administration & dosage; Benzimidazoles - pharmacokinetics; Bioavailability; Biochemistry; Biological Availability; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cellulose; Cross-Over Studies; Delayed-Action Preparations; Dissolution; Drug Compounding; Drug dosages; Fasting; Food-Drug Interactions; Humans; Hypromellose Derivatives - chemistry; Linear Models; Medical Law; Neoplasms - drug therapy; Ovarian cancer; Pharmacology/Toxicology; Pharmacy; Plasma; Product development; Research Paper; Solid tumors; Solubility; Tablets; Tumors; correlations (IVIVC); pharmacokinetics; veliparib; extended-release formulation; dissolution; in vitro/in vivo correlations (IVIVC)
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-017-2133-3

Purpose The aim of the current manuscript is to develop and validate a level A in vitro-in vivo correlation (IVIVC) for veliparib extended-release (ER) tablet formulations. Methods The in vitro release profiles of veliparib formulations were determined using USP Dissolution Apparatus 2 with 900 mL of 0.1 N HCl at 75 rpm. In a clinical study, 24 subjects with solid tumors received one of the ER formulations (200 mg): fast (Formulation A), intermediate (Formulation B), and slow (Formulation C), and two 100 mg immediate release capsules (Formulation D). Blood samples were collected over a period of 48 h and analyzed using LCMS/MS. A linear correlation model was developed using fraction absorbed and fraction dissolved data from formulations A and B. Besides assessing internal predictability, external predictability was evaluated using formation C. Prediction errors were estimated for maximum observed plasma concentration (C max ) and area under the plasma-concentration time curve from zero to last measured time point (AUC t ) to determine the predictive ability of the correlation. Results There was a significant linear relationship (r 2  = 0.944) between the fraction of drug absorbed and the fraction of drug dissolved. The prediction error using the internal validation for C max and AUC t were below 15% for the individual formulations and below 10% for the average. The prediction error in AUC t and C max for formulation C was 5% and 11%, respectively. Conclusions A level A IVIVC for the veliparib ER tablet formulation was established. The IVIVC may allow the associated dissolution data to be used as a surrogate for bioavailability.