Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1997-04-04
1999-02-09
Azpuru, Carlos A.
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424502, 264 41, 264 46, A61K 950, B01J 1302
Patent
active
058691030
DESCRIPTION:
BRIEF SUMMARY
RELATED APPLICATIONS
Priority is claimed under 35 U.S.C. .sctn. 119 to PCT/GB95/01426, filed Jun. 19, 1995, which corresponds to GB 94112273.6, filed Jun. 18, 1994.
FEDERALLY SPONSORED RESEARCH
Not applicable.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to polymer microparticles for administering active agents, and to a method for making such particles.
2. Background Art
It is possible to deliver therapeutic agents in the form of drugs and vaccines to the body by a variety of routes that include parenteral and nonparenteral access. The products of biotechnology represent a special class of materials. Today the pharmaceutical scientist is faced with the problem of delivering therapeutically active materials in the form of peptides and proteins, carbohydrates, oliogonucleotides and DNA.
Considerable interest exists in the use of colloidal particles for the delivery of therapeutically active materials in the form of proteins and peptides and for vaccine formulation. Various biodegradable polymers have been investigated as therapeutic carriers, including serum albumin beads, polyacryl starch microparticles, polyacrylamide, microparticles, poly(butyl-2-cyanocrylate) nanoparticles and polylactide co-glycolide microparticles (Florence et al). In the case of albumin and polyacryl starch, antibody responses were induced to the carriers as well as to the specific antigens entrapped therein. Problems of toxicity associated with polyacrylamide and poly(butyl-2-cyanoacrylate) limit the use of these polymers as antigen delivery systems.
Microparticles based upon resorbable copolymers of polylactide and polyglycolide have been widely investigated for drug delivery (Watts, et al) and are now finding increasing application for the delivery of the products of biotechnology (especially peptides and proteins) (Kwong, et al and Wang, et al). These synthetic polyesters are approved for human use and have a 25 year history of safety. Injected poly(DL-lactide-co-glycolide) (PLG) microparticles exhibit good biocompatibility and induce only a minimal inflammatory response. The lactide copolymers such as PLG are good candidates for the development of controlled release drug systems and vaccines. They biodegrade through hydrolysis of ester linkages to yield the normal body constituents lactic acid and glycolic acid. The degradation rate of lactide copolymers is controlled by various factors including molecular weight, lactide: glycolide ratio and polymer crystallinity and can be varied from several weeks to over a year, thus potentially allowing control over the time and rate of vaccine release. Carriers may therefore be designed to release entrapped antigen at certain intervals after immunization when booster doses are normally administered.
A large number of microencapsulation techniques have been developed using PLG, such as film casting, moulding, spray drying and extrusion, but the most common is the solvent evaporation technique (Fong, et al., and Bodmeier et al.,). Although the oil-in water (O/W) emulsion/solvent evaporation technique has been used successfully by several groups to entrap hydrophobic substances such as progesterone, poor encapsulation efficiency results for moderately water-soluble and water soluble drugs due to partition into the aqueous continuous phase (Benita. et al.,). This presents a major problem in drug and vaccine delivery.
Protein encapsulation in PLG microparticles has been attempted previously using oil-in oil (O/O) and O/W techniques wherein dried protein is first dispersed in a solution of PLG (Alonso. et al). In the O/O technique, the dispersion may be emulsified in silicone oil containing SPAN 85.TM. as a stabiliser. The addition of petroleum ether subsequently results in solvent extraction and precipitation of the microparticles. Although protein loadings are close to the theoretical maximum, the particle size tends to be large ( around 500 .mu.m ) and the particle shape irregular. Leelarasamee et al described a solvent partitioning method which i
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Coombes Alan Gerald
Davis Stanley Stewart
Jenkins Paul George
Yeh Ming-Kung
Azpuru Carlos A.
Danbiosyst UK Limited
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