Predicting hydrophilic drug encapsulation inside unilamellar liposomes.
A mathematical model has been developed to predict the encapsulation efficiency of hydrophilic drugs in unilamellar liposomes, and will be useful in formulation development to rapidly achieve optimized formulations. This model can also be used to compare drug encapsulation efficiencies of liposomes prepared via different methods, and will assist in the development of suitable process analytical technologies to achieve real-time monitoring and control of drug encapsulation during liposome manufacturing for hydrophilic molecules. Liposome particle size as well as size distribution, lipid concentration, lipid molecular surface area, and bilayer thickness were used in constructing the model. Most notably, a Log-Normal probability function was utilized to account for sample particle size distribution. This is important to avoid significant estimation error. The model-generated predictions were validated using experimental results as well as literature data, and excellent correlations were obtained in both cases. A Langmuir balance study provided insight regarding the effect of media on the liposome drug encapsulation process. The results revealed an inverse correlation between media ionic strength and lipid average molecular area, which helps to explain the phenomenon of inverse correlation between media ionic strength and drug encapsulation efficiency. Finally, a web application has been written to facilitate use of the model allowing calculations to be easily performed. This model will be useful in formulation development to rapidly achieve optimized formulation.
Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd U3092, Storrs, CT 06269, United States. xiaoming.xu@me.com
Xiaoming
X
Xu
Mansoor A
MA
Khan
Diane J
DJ
Burgess
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004339:Drug Compounding; D005240:Feasibility Studies; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry*; D008956:Models, Chemical; D015233:Models, Statistical; D036103:Nanotechnology; D063065:Organophosphonates / Q000737:chemistry*; D009994:Osmolar Concentration; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D011407:Propane / Q000031:analogs & derivatives / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D000068698:Tenofovir; D053835:Unilamellar Liposomes
C519974:1,2-dipalmitoyl-3-trimethylammonium-propane; D008055:Lipids; D063065:Organophosphonates; D010713:Phosphatidylcholines; D000644:Quaternary Ammonium Compounds; D053835:Unilamellar Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D000068698:Tenofovir; C010942:1,2-distearoyllecithin; D000225:Adenine; D011407:Propane; D004134:Dimyristoylphosphatidylcholine