Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Patent
1995-06-02
1997-02-18
Azpuru, Carlos
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
424451, 424489, 264 41, 42840221, 42840224, 514885, 514963, 530806, A61K 950, A61K 948, A61K 914, B01J 1302
Patent
active
056039603
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a method for producing microparticles useful in the formulation of pharmaceutical compositions. The present invention further relates to a method of immunizing a mammal against diseases comprising administering to a mammal an effective amount of antigen containing microparticles. In particular, the present invention describes a method of potentiating an immune response in a mammal comprising administering an effective amount of a pharmaceutical composition containing said microparticles to a mammal. The present invention further describes a vaccine comprising a pharmaceutical composition containing said microparticles. An antigen delivery system comprising microparticles containing entrapped antigens is further described by the present invention. A pharmaceutical composition comprising microparticles and a pharmaceutical carrier is also provided.
BACKGROUND OF THE INVENTION
Interest in the administration of both therapeutic and antigenic proteins and peptides has grown considerably in recent years due to improvements in the quality and quantity of recombinant proteins and synthetic peptides now available. These molecules, however, suffer the disadvantage of having short biological half lives following parenteral administration and are degraded in the intestine following oral administration. Furthermore, if orally or nasally administered, these molecules show poor absorption through the mucous membranes.
Biodegradable polymers such as polylactide-co-glycolides (PLG) have been used to encapsulate proteins and peptides and other drugs for parenteral and/or oral delivery in order to try to achieve a stable and therapeutically adequate level of drug over an extended period of time. Previous investigators have claimed that antigenic protein and peptides can be encapsulated in microcapsules to deliver "pulses" (i.e. "intermittent doses") of antigenic material for the development of vaccines (see e.g. U.S. Pat. No. 5,075,109 to Tice et al.). The use of microencapsulation to protect sensitive bioactive agents against degradation is well known in the art, however, the use of biodegradable microparticles in controlled release delivery systems seldom results in satisfactory release profiles.
The drug release pattern for a microcapsule is dependent upon numerous factors. For example, the type of drug encapsulated and the form in which it is present (i.e. liquid or powder) may affect the drugs release pattern. Another factor which may affect the drug release pattern is the type of polymer used to encapsulate the drug. Other factors affecting the drug release pattern include the drug loading, the manner of distribution in the polymer, the particle size and the particle shape.
There are several methods known for the production of microparticles. Typical methods for producing microparticles include solvent evaporation and phase separation. With production methods such as solvent evaporation, as much as 50% w/w of insoluble or poorly soluble materials, may be incorporated in biodegradable microparticles. However, with more water soluble materials, such as peptides, drug loadings have generally been much lower.
Consequently, the use of phase separation for production of microparticles may be better suited for the formulation of microparticles containing more water soluble compounds. Phase separation methods of microparticle preparation allow a more efficient incorporation of drugs and can easily be scaled up for industrial purposes. The process of phase separation usually employs an emulsion or a suspension of the drug particles in a solution of a high molecular weight polymer and an organic polymer solvent. A non-solvent is then added to the suspension or emulsion, causing the polymer to separate from solution and to encapsulate the suspended drug particles or droplets containing them. The resulting microparticles (which are still swollen with solvent) are then normally hardened by a further addition of a non-solvent or by some other process which strengthens and i
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Ruiz et al, International Journal of Pharmaceutics, 49:69-77 (1889) "Microencapsulation of peptide: a study of the phase separation of poly(D,L,-lactic acid-co-glycolic acid) copolymers 50/50 by silicone oil".
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Davis Stanley S.
McGee John P.
O'Hagan Derek T.
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