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Insulin-entrapped liposomes cause dose-dependent hypoglycemia. Choudhari et al. prepared liposomes with varying composition
by two methods: solvent evaporation hydration and solvent spherule evaporation (28). Liposomes containing lecithin 100 mg,
cholesterol 20 mg, insulin 150 units, and Tween 1% v/v were found to be most effective. The effect of insulin-liposome was
prolonged in diabetes-induced rabbits than that of normal rabbits. The pharmacodynamics of the insulin-liposome system was
comparable with the action of 1 U/kg of insulin administered subcutaneously.
Coated liposomes. In another study, insulin liposomes were prepared by reversed phase separation and coated with chitosan of various molecular
weights and concentrations (29). Chitosan coating was carried out by incubation of the liposomal suspensions with the chitosan
solution. These chitosan-coated liposomes were administered to mice perorally and their hypoglycemic efficacy was determined.
The insulin liposomes coated by 0.2% chitosan (MW 1000 kDa) showed maximum hypoglycemic efficacy. The minimum blood-glucose
level and the hypoglycemic effect lasted for 4 h. Chitosan-coated liposomes also reduced tryptic digestion on insulin and
enhanced enteral absorption of insulin. The molecular weights and concentrations of chitosan had significant effect on hypoglycemic
efficacy of chitosan-coated insulin liposomes after oral administration to healthy mice.
In another study, insulin was bound covalently to the outer surface of multilamellar liposomes loaded with spin label (30).
Electron spin resonance controlled encapsulation of the label tempocholine-nitroxide within the aqueous phases of liposomes.
The binding of insulin was performed using the Carlsson's heterobifunctional reagent: N-succinimidyl 3-(2-pyridyldithio) propionate.
The coupling method resulted in efficient attachment of 2.64.10(-4) mole of insulin per mole of phospholipid. Liposome coupled
insulin retained its antigenic specificity as proved by radio immune assay.
DepoFoam (Pacira Pharmaceuticals, Parsippany, NJ) technology consists of novel multivesicular liposomes characterized by their
unique structure of multiple nonconcentric aqueous chambers surrounded by a network of lipid membranes. Ye et al. demonstrated
that DepoFoam technology can be used to develop sustained-release formulations of insulin with high loading (31). The data
showed these formulations had a number of advantages, including high drug loading, high encapsulation efficiency, low content
of free drug in the suspension, little chemical change in the drug caused by the formulation process, narrow particle-size
distribution, and spherical particle morphology.
S. Dhawan is a senior manager of advanced drug delivery and research at Panacea Biotech and a faculty member at UGC-CAS Pharmaceutical Science, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, INDIA.
Articles by S. Dhawan
S. Chopra
Sunny Chopra is a senior reesearch fellow in the department of pharmaceutical sciences at Jamia Hamdard University, New Delhi, India.
Articles by S. Chopra
R. Kapil
Rishi Kapil is a senior research fellow at UGC-CAS Pharmaceutical Science, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, INDIA.
Articles by R. Kapil
D. Kapoor
Deepak Kapoor is a senior research fellow all at UGC-CAS Pharmaceutical Science, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, INDIA.
Articles by D. Kapoor
Survey
How does your company apply quality-by-design (QbD) principles to manufacturing processes?
To all processes for both new and legacy products
19%
To all process for new products only
14%
To select process for new products only
24%
To select processes for both new and legacy products
