title: Understanding and predicting the impact of critical dissolution variables for nifedipine immediate release capsules by multivariate data analysis.
abstract: In this study the selection of in vivo predictive in vitro dissolution experimental set-ups using a multivariate analysis approach, in line with the Quality by Design (QbD) principles, is explored. The dissolution variables selected using a design of experiments (DoE) were the dissolution apparatus [USP1 apparatus (basket) and USP2 apparatus (paddle)], the rotational speed of the basket/or paddle, the operator conditions (dissolution apparatus brand and operator), the volume, the pH, and the ethanol content of the dissolution medium. The dissolution profiles of two nifedipine capsules (poorly soluble compound), under conditions mimicking the intake of the capsules with i. water, ii. orange juice and iii. an alcoholic drink (orange juice and ethanol) were analysed using multiple linear regression (MLR). Optimised dissolution set-ups, generated based on the mathematical model obtained via MLR, were used to build predicted in vitro-in vivo correlations (IVIVC). IVIVC could be achieved using physiologically relevant in vitro conditions mimicking the intake of the capsules with an alcoholic drink (orange juice and ethanol). The multivariate analysis revealed that the concentration of ethanol used in the in vitro dissolution experiments (47% v/v) can be lowered to less than 20% v/v, reflecting recently found physiological conditions.
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Mercuri
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Pagliari
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom.
authors.forename: F
authors.initials: F
authors.lastname: Baxevanis
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom.
authors.forename: R
authors.initials: R
authors.lastname: Fares
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath, United Kingdom. Electronic address: n.fotaki@bath.ac.uk.
authors.forename: N
authors.initials: N
authors.lastname: Fotaki
mesh_terms: D002214:Capsules; D032084:Citrus sinensis; D005215:Fasting; D000067030:Fruit and Vegetable Juices; D005750:Gastric Juice / Q000737:chemistry; D016014:Linear Models; D015999:Multivariate Analysis; D009543:Nifedipine / Q000737:chemistry*; D012995:Solubility
chemical_list: D002214:Capsules; D009543:Nifedipine
keywords: Biorelevant dissolution; Design of experiments; Ethanol; IVIVC; Multivariate data analysis; QbD