Development and evaluation of liposome process methods and in-vitro drug release rate technique

Sriram Vemuri, University of Rhode Island


Liposome drug delivery systems are now being developed for a variety of drugs. Scale-up of processes to larger size batches is often a monumental task. An eight step method to scale-up the liposome process from laboratory scale to large scale process is shown. A pH gradient across liposome bilayers was established in order to load a model drug (orciprenaline sulphate) into liposome vesicles. This method of liposome loading resulted in yields as high as 80-85% encapsulation. In this process a diafiltration technique was successfully used to remove the excess orciprenaline sulphate present in the external medium. Finally, drug loaded liposomes were lyophilized using lactose as an internal and external liposomal cryoprotectant. Five month stability data for the liposomes is reported. Liposomes prepared by the pH gradient method showed high encapsulation efficiency. Upon storage at $\rm 2{-}8\sp\circ C$ the vesicle size increased and encapsulation efficiency decreased with time. This phenomenon is attributed to gradual fusion of liposomes and loss of drug to the extra-liposomal media.^ Feasibility studies were undertaken in order to explore the use of size exclusion chromatography, as a large scale process, to separate liposomes from free drug in a liposome preparation. Chromatographic conditions were optimized to scale up the process to a larger batch size, successfully. Washing of liposomes with normal saline and subsequent separation of drug loaded liposomes is also a viable separation technique for scale-up activities.^ An in vitro method was developed to determine the drug release from a liposome preparation. Three batches of liposomes were evaluated for drug release over a 24 hour period in an end-over-end tumbler device. Intra and inter day precision studies indicate good reproducibility for this test method. This method is easy to use.^ The results from this study have enhanced our understanding of the liposome manufacturing and scale-up methods. It has provided information on the drug-release method that is readily adoptable to quality control environment. In addition, the data produced and presented in this dissertation reveals that it is possible to obtain near 100% encapsulation of orciprenaline sulphate. ^

Subject Area

Chemistry, Biochemistry|Chemistry, Pharmaceutical|Health Sciences, Pharmacy

Recommended Citation

Sriram Vemuri, "Development and evaluation of liposome process methods and in-vitro drug release rate technique" (1997). Dissertations and Master's Theses (Campus Access). Paper AAI9805256.