title: Optimizing the taste-masked formulation of acetaminophen using sodium caseinate and lecithin by experimental design.
abstract: In a previous study of ours, the association of sodium caseinate and lecithin was demonstrated to be promising for masking the bitterness of acetaminophen via drug encapsulation. The encapsulating mechanisms were suggested to be based on the segregation of multicomponent droplets occurring during spray-drying. The spray-dried particles delayed the drug release within the mouth during the early time upon administration and hence masked the bitterness. Indeed, taste-masking is achieved if, within the frame of 1-2 min, drug substance is either not released or the released amount is below the human threshold for identifying its bad taste. The aim of this work was (i) to evaluate the effect of various processing and formulation parameters on the taste-masking efficiency and (ii) to determine the optimal formulation for optimal taste-masking effect. Four investigated input variables included inlet temperature (X1), spray flow (X2), sodium caseinate amount (X3) and lecithin amount (X4). The percentage of drug release amount during the first 2 min was considered as the response variable (Y). A 2(4)-full factorial design was applied and allowed screening for the most influential variables i.e. sodium caseinate amount and lecithin amount. Optimizing these two variables was therefore conducted by a simplex approach. The SEM and DSC results of spray-dried powder prepared under optimal conditions showed that drug seemed to be well encapsulated. The drug release during the first 2 min significantly decreased, 7-fold less than the unmasked drug particles. Therefore, the optimal formulation that performed the best taste-masking effect was successfully achieved.
authors.affiliation: Université Lille Nord de France, College of Pharmacy, 3 rue du Professeur Laguesse, BP 83, 59006 Lille Cedex, France.
authors.forename: Thanh Huong
authors.initials: TH
authors.lastname: Hoang Thi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Lemdani
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Flament
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D002364:Caseins / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D003890:Desiccation / Q000379:methods; D004339:Drug Compounding; D054709:Lecithins / Q000737:chemistry*; D012107:Research Design; D013649:Taste
chemical_list: D002364:Caseins; D054709:Lecithins; D000082:Acetaminophen
keywords: Component segregation; Factorial design; Pediatric formulation; Simplex optimization; Spray-drying; Taste-masking