Abstract: Multivesicular liposomes are prepared at commercial scales by combining a first w/o emulsion with a second aqueous solution to form a w/o/w emulsion using a static mixer. Solvent is removed from the resulting emulsion to form multivesicular liposome-containing compositions. Further optional process steps include primary filtration and secondary cross-flow filtration. The products produced according to the processes of the invention can be produced through a series of aseptic steps.

Abstract: A drug delivery system provides sustained-release delivery of therapeutic biologically active compounds administered epidurally. In the preferred embodiment the biologically active compound is an opioid, which is encapsulated within the non-concentric internal aqueous chambers or bilayers of multivesicular liposomes. The opioid is released over an extended period of time when the liposomes are introduced epidurally as a single dose for sustained analgesia.

Abstract: A drug delivery system provides sustained-release delivery of therapeutic biologically active compounds administered epidurally. In the preferred embodiment the biologically active compound is an opioid, which is encapsulated within the non-concentric internal aqueous chambers or bilayers of multivesicular liposomes. The opioid is released over an extended period of time when the liposomes are introduced epidurally as a single dose for sustained analgesia.

Abstract: Pharmaceutical compositions that enable the release of a physiologically active substance over a prolonged period of time following administration to a patient are described. The pharmaceutical compositions are provided by encapsulation of a physiologically active substance into a matrix comprising biodegradable polymers and lipids. The rate of release of the physiologically active substance from the pharmaceutical composition is controlled by varying the ratio of the polymer to the lipid. The compositions can be stored in an aqueous suspension or as a solid dosage form. The physiologically active substances include small molecules, peptides, proteins, nucleic acids and vaccines. The biodegradable polymers include homopolymers, or random or block copolymers. The lipids include phospholipids, cholesterol and glycerides.

Abstract: Disclosed are multivesicular liposomes (MVLs) containing IGF-I with substantially full bioavailability, wherein the loading of the IGF-I into the liposomes is modulated by adjusting the osmolarity of the aqueous component into which the agents are dissolved prior to encapsulation. In the making of MVLs, the process involves dissolving the IGF-I, an osmolarity excipient, and a pH modifying agent sufficient to solubilize the IGF-I in a first aqueous component used during manufacture of the MVLs. To increase the loading of the IGF-I, the osmolarity of the aqueous component used during manufacture of the MVLs is reduced, whereas the osmolarity of the aqueous component is increased to obtain the low load formulations. The rate of release of the active agent into the surrounding environment in which the liposomes are introduced can be simultaneously controlled by incorporating into the lipid component used in the formulation at least one long chain amphipathic lipid.

Abstract: Pharmaceutical compositions that enable the release of a physiologically active substance over a prolonged period of time following administration to a patient are described. The pharmaceutical compositions are provided by encapsulation of a physiologically active substance into a matrix comprising biodegradable polymers and lipids. The rate of release of the physiologically active substance from the pharmaceutical composition is controlled by varying the ratio of the polymer to the lipid. The compositions can be stored in an aqueous suspension or as a solid dosage form. The physiologically active substances include small molecules, peptides, proteins, nucleic acids and vaccines. The biodegradable polymers include homopolymers, or random or block copolymers. The lipids include phospholipids, cholesterol and glycerides.

Abstract: The efficiency of encapsulating a drug into a liposomal formulation is increased by use of a lipid having a carbon chain containing from about 13 to about 28 carbons during preparation of the liposomes. Preferably the liposomes are multivesicular liposomes.

Abstract: The efficiency of encapsulating a drug into a liposomal formulation is increased by use of a lipid having a carbon chain containing from about 13 to about 28 carbons during preparation of the liposomes. Preferably the liposomes are multivesicular liposomes.

Abstract: The efficiency of encapsulating a drug into a liposomal formulation is increased by use of a lipid having a carbon chain containing from about 13 to about 28 carbons during preparation of the liposomes. Preferably the liposomes are multivesicular liposomes.

Abstract: A multivesicular liposome composition containing at least one acid other than a hydrohalic acid and at least one biologically active substance, the vesicles having defined size distribution, adjustable average size, internal chamber size and number, provides a controlled release rate of the biologically active substance from the composition. A process for making the composition features addition of a non-hydrohalic acid effective to sustain and control the rate of release of an encapsulated biologically active substance from the vesicles at therapeutic levels in vivo.

Abstract: Disclosed is a method for making liposomes, for example multivesicular liposomes (MVLs), containing one or more biologically active agents, wherein the loading of the active agents into the liposomes is modulated by adjusting the osmolarity of the aqueous component into which the agents are dissolved prior to encapsulation. To increase the loading of the active agent, the osmolarity of the aqueous component is reduced, and to decrease the loading of the active agent, the osmolarity of the aqueous component is increased. In the making of MVLs, the process involves dissolving the active agent and an optional osmotic excipient in a first aqueous component encapsulated within the liposomes. For any given concentration of drug, the osmolarity of the first aqueous component can be adjusted by increasing or decreasing the concentration or molecular weight of the osmotic excipients used therein.

Abstract: Disclosed are multivesicular liposomes containing biologically active substances, and having defined size distribution, adjustable average size, adjustable internal chamber size and number, and a modulated release of the biologically active substance. The liposomes are made by a process comprising dissolving a lipid component in volatile organic solvents, adding an immiscible aqueous component containing at least one biologically active substance to be encapsulated, and adding to either or both the organic solvents and the lipid component, a hydrochloride effective to control the release rate of the biologically active substance from the multivesicular liposome. A water-in-oil emulsion is made from the two components, the emulsion is immersed into a second aqueous component, and then divided into small solvent spherules which contain even smaller aqueous chambers. The solvents arc finally removed to give an aqueous suspension of multivesicular liposomes encapsulating biologically active substances.

Abstract: The invention provides a method for obtaining local anesthetics encapsulated in liposomes, such as multivesicular liposomes, with high encapsulation efficiency and slow release in vivo. When the encapsulated anesthetic is administered as a single intracutaneous dose, the duration of anesthesia and half-life of the drug at the local injection site is increased as compared to injection of unencapsulated anesthetic. The maximum tolerated dose of the encapsulated anesthetic is also markedly increased in the liposomal formulation over injection of unencapsulated anesthetic. These results show that the liposomal formulation of local anesthetic is usefuil for sustained local infiltration and nerve block anesthesia.

Abstract: The efficiency of encapsulating a drug into a liposomal formulation is increased by use of a lipid having a carbon chain containing from about 13 to about 28 carbons during preparation of the liposomes. Preferably the liposomes are multivesicular liposomes.

Abstract: Disclosed are multivesicular liposomes (MVL's) containing biologically active substances, the multivesicular liposomes having defined size distribution, adjustable average size, adjustable internal chamber size and number, and a controlled and variable release rate of the biologically active substance. The process involves encapsulating at least one biologically active substance and optionally an osmotic spacer in a first aqueous component encapsulated within the liposomes. The rate of release of the active substance into the surrounding environment in which the liposomes are introduced can be decreased by increasing the osmolarity of the first aqueous component or increased by decreasing the osmolarity.