Application of statistical experimental design to study the formulation variables influencing the coating process of lidocaine liposomes.
In this paper, we have used statistical experimental design to investigate the effect of several factors in coating process of lidocaine hydrochloride (LID) liposomes by a biodegradable polymer (chitosan, CH). These variables were the concentration of CH coating solution, the dripping rate of this solution on the liposome colloidal dispersion, the stirring rate, the time since the liposome production to the liposome coating and finally the amount of drug entrapped into liposomes. The selected response variables were drug encapsulation efficiency (EE, %), coating efficiency (CE, %) and zeta potential. Liposomes were obtained by thin-layer evaporation method. They were subsequently coated with CH according the experimental plan provided by a fractional factorial (2(5-1)) screening matrix. We have used spectroscopic methods to determine the zeta potential values. The EE (%) assay was carried out in dialysis bags and the brilliant red probe was used to determine CE (%) due to its property of forming molecular complexes with CH. The graphic analysis of the effects allowed the identification of the main formulation and technological factors by the analysis of the selected responses and permitted the determination of the proper level of these factors for the response improvement. Moreover, fractional design allowed quantifying the interactions between the factors, which will consider in next experiments. The results obtained pointed out that LID amount was the predominant factor that increased the drug entrapment capacity (EE). The CE (%) response was mainly affected by the concentration of the CH solution and the stirring rate, although all the interactions between the main factors have statistical significance.
González-Rodríguez
M L
ML
Department of Pharmaceutical Technology, University of Seville, C/ Prof. García González, 2, 41012 Seville, Spain. malugoro@us.es
Barros
L B
LB
Palma
J
J
González-Rodríguez
P L
PL
Rabasco
A M
AM
D000779:Anesthetics, Local / Q000737:chemistry*; D001672:Biocompatible Materials; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D004339:Drug Compounding; D008012:Lidocaine / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D015233:Models, Statistical; D012107:Research Design; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D014867:Water / Q000737:chemistry
D000779:Anesthetics, Local; D001672:Biocompatible Materials; D008055:Lipids; D008081:Liposomes; D014867:Water; D048271:Chitosan; D008012:Lidocaine