MXPA00011650A - Drug delivery system comprising a tightly compacted solid medicament stock - Google Patents
Drug delivery system comprising a tightly compacted solid medicament stockInfo
- Publication number
- MXPA00011650A MXPA00011650A MXPA/A/2000/011650A MXPA00011650A MXPA00011650A MX PA00011650 A MXPA00011650 A MX PA00011650A MX PA00011650 A MXPA00011650 A MX PA00011650A MX PA00011650 A MXPA00011650 A MX PA00011650A
- Authority
- MX
- Mexico
- Prior art keywords
- drug delivery
- delivery system
- liposomes
- active agent
- highly compacted
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 84
- 229940079593 drugs Drugs 0.000 title claims abstract description 56
- 239000007787 solid Substances 0.000 title claims abstract description 30
- 239000002502 liposome Substances 0.000 claims abstract description 61
- 239000000463 material Substances 0.000 claims abstract description 46
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 41
- 239000000969 carrier Substances 0.000 claims abstract description 22
- 239000002245 particle Substances 0.000 claims abstract description 18
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- 229920003013 deoxyribonucleic acid Polymers 0.000 claims description 10
- GUBGYTABKSRVRQ-UUNJERMWSA-N Lactose Natural products O([C@@H]1[C@H](O)[C@H](O)[C@H](O)O[C@@H]1CO)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 GUBGYTABKSRVRQ-UUNJERMWSA-N 0.000 claims description 9
- 239000008101 lactose Substances 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
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Abstract
A drug delivery system comprising a tightly compacted solid medicament stock having an essentially isotropic solid state structure comprising an active agent and which stock is suitable for the generation of inhalable particles containing said active agent, wherein the tightly compacted solid medicament stock comprises at least one active agent which is associated with a particulate carrier material, especially comprising liposomes.
Description
DRUG SUPPLY SYSTEM COMPRISING A VERY COMPACT SOLID MEDICAMENTAL MATERIAL
FIELD OF THE INVENTION This invention has to do with a drug delivery system comprising a highly compacted solid medicament material, with a method for the preparation of the medicament material, as well as with the use of the solid medicament material of the invention.
BACKGROUND OF THE INVENTION Pulmonary application by inhalation or insufflation of drug substances has been achieved, for example, by administration of the respective drug as an aerosol or by inhalation of powder. Since aerosols are often based on fluorohydrocarbons or other hydrocarbons, it is generally desired to substitute aerosols for the inhalation of dust. EP 0 407 028 discloses a device for administering drugs in powder form by inhalation. The disadvantages of the disclosed device and the medicament are that the deposit of solid can not be handled safely, since only low pressures are applied for compaction. The compacted body is brittle and can disintegrate when not handled carefully. WO 94/14490 and WO 93/29165 have to do with a system for the application of powder or fine particles by inhalation. The compliance device 5 with WO 93/24165 allows the generation of particles from a compacted tablet having an isotropic substructure. The medicament compacted in accordance with WO 94/14490 is manufactured by applying pressures of up to 500 MPa, thus, they are applied
Some orders of magnitude higher than those applied in EP 0 407 028. The compacted body according to WO 94/14490 is advantageous in comparison with the compacted body according to EP 0 407 028. This allows, for example, easy to use, because, due to its
compactness, does not disintegrate. Furthermore, it does not tend to absorb water compared to the less compacted body in accordance with EP 0 407 028. Liposomes are well-known carriers of pharmaceutical compositions. The advantages of the application
of medicines by means of liposomes have been subject to several revisions. The pulmonary application of liposomes has allowed important advances in the treatment of infectious diseases and asthma (compare, for example, H. Schreier, Pulmonary aplications of liposomes, in
"Medical applications of liposomes", Paphadjopoulos & Lasic
P1167
• - • * - • • • • • "(eds.), Elsevier, 1997; RJ Gonzalez-Rothi & H. Schreier, Pulmonary delivery of liposome encapsulated drugs in asthma therapy, Clin. Immunother. 4, 331-337, 1995; H. Schreier, R.J. Gonzalez-Rothi, A. Stecenko, Pulmonary delivery of liposomes, J. Controlled Relay 24, 209-223, 1993). The diseased lung is particularly accessible for topical therapy by inhaling drug aerosols (H. Schreier and SM Sawyer, Liposomal DNA vectors for cystic fibrosis gene therapy, Current applications, limitations, and future directions, Adv. Drug. Del. Rev. 19, 73-87, 1996, L. Gagné &H. Schreier, Aerosolizat ion of plasmid DNA, Protective effects of solute condensing agents, and liposome carriers, Proceed, Intern Symp. Control, Reagent Bioact. Mater. 1997). While anti-asthmatic and antiallergic agents delivered by metered-dose inhalers (MDI's) are widely used, only recently have aerosolized antimicrobials been introduced, for example, aminoglycosides for the management of cystic fibrosis, ribavirin for respiratory syncytial virus infections in infants and pentamidine for the treatment of pulmonary infections due to Pneumocystis carinii in immunocompromised patients (WO 96/27393, H. Schreier, KJ McNicol, M. Ausborn, DW Soucy, H. Derendorf, AA Stecenko, RJ Gonzalez-Rothi, Pulmonary
P1167 delivery of amikacin liposomes and acute liposome toxicity in the sheep, Int. J. Pharmaceut. 87, 183-193, 1992). Other particulate carriers, which are comparable to liposomes, have been described in the art. These include microspheres, nanoparticles, large porous particles, molecules coated with polymer by pulsative laser, artificial viral envelopes, etc. When alternative particulate carriers are used, these are generally prepared as is known in the art. Thus, microspheres that are used to deliver a very broad range of therapeutic or cosmetic agents are prepared as described in, for example, WO 95/15118. In some cases, nanoparticles can be used, as long as they can be loaded with a sufficient amount of the active agent and can be administered to the lower respiratory tract, in accordance with this invention. These can be prepared in accordance with methods known in the art, such as, for example, those described by Heyder (GSF München) in "Drugs delivered to the lung", Abstracts IV, Hilton Head Island Converence, May 1998. Methods that use a device for the deposition by pulsatile laser (PLD for its acronym in
P1167 English) and a polymeric white to apply coatings to the drug powders in a brief non-aqueous process, are also suitable for the formation of; particulate preparations in accordance with this invention. These have been described in, for example, Taiton et al., "Novel Coating Method for Improved Dry Delivery," Univ. Of Florida UF 1887 (1998). An additionally adequate delivery system utilizes Large Porous Particles, as revealed by David A. Edwards and collaborators in "Large Porous Particles for Pulmonary Drug Delivery" (Science, June 20, 1997, Vol. 276, pp. 1868-1871). Hereinafter, where reference is made to liposomes, it should be understood that the invention can be operated using these alternative and suitable particulate carriers, combined with or instead of liposomes. The pulmonary supply of drugs is complicated due to: (i) the need to train patients for breathing and inhalation in coordinated forms of aerosols, (ii) the rapid absorption of most drugs, which requires a frequent dosing, which is often responsible for systemic side effects, (iii) the low aqueous solubility of the drugs which can cause local irritation and inflammation in the airways or completely avoid the use of aerosols and (iv) the low cytosolic penetration of the drug to treat intracellular pathogens. An illustrative aspect of these problems is the controversial use of ribavirin aerosols that require excessive aerosolization (in "aerosol booth"), frequent monitoring of valves, pipe changes and suction with endotracheal tube to avoid precipitation of the drug, while at the same time the clinical results are modest. Another therapeutically undesirable aspect of pulmonary drug delivery is the rapid absorption of most drugs in the lung, which necessitates a frequent dosing of, for example, bisoncodilators, and corticosteroids. Particulate carriers, especially liposomes alleviate some of the problems encountered in conventional aerosol delivery, due to their ability to: (i) serve as a solubilization matrix of agents that solubilize in a deficient manner; (ii) act as prolonged release pulmonary deposits and (iii) facilitate the intracellular delivery of drugs, specifically alveolar macrophages. Consequently, liposomes can provide a means to: (i) prevent local irritation of lung tissue and reduce pulmonary toxicity, (ii) prolong local levels of the therapeutic drug and (iii) generate intracellular concentrations of the drug in, for example, infected alveolar macrophages. Drugs that have been considered for pulmonary delivery by liposomes include anticancer drugs (antimicrobials, peptides, enzymes, anti-asthmatic and antiallergic compounds as well as cromolyn sodium), immunomodulatory agents, immunosuppressants, antiviral and antimycobacterial agents as well as gene constructs have also been considered. object of the present invention is to provide a drug delivery system for the pulmonary delivery of active agents associated with liposomes or other particulate carriers Another object of the invention is to provide a highly compacted solid medicament material which is suitable for the generation of inhalable particles that contain active agents.
SUMMARY OF THE INVENTION The drug delivery system of the present invention comprises a highly compacted solid medicament material having an essentially isotropic solid state structure comprising an active agent and this material is suitable for the generation of inhalable particles containing the agents active ingredients, wherein the highly compacted solid medicament material comprises at least one active agent that is associated with the particulate carrier, such as liposomes. The present invention is based, inter alia, on the unexpected finding that liposomes can withstand the high pressures that must be applied to form the highly compacted solid drug material containing liposomes. Additionally it is surprising that the carriers, especially the liposomes, which were loaded with an active agent or associated with an active agent, are not completely emptied or destroyed, when a powder containing, for example, liposomes is generated by, for example, , methods of abrasion performed with a device as disclosed in WO 93/24165 (which is incorporated by reference) from this highly compacted medicament material. Preferably, pressures of up to 500 MPa are applied, in accordance with WO 94/14490 (which is also incorporated by reference). Surprisingly, the liposomes that associate with the agent survive both the compaction process (as in WO 97/14490) and the abrasion process (as in WO 93/24165) almost intact and apparently unchanged.
DETAILED DESCRIPTION OF THE PREFERRED MODE In accordance with the invention, it is preferred that the active agent associated with the carriers be disposed within the carrier and / or disposed on the carrier. Preferably, the active agent is incorporated into, for example, liposomes or the liposomes are loaded with the active agent, i.e., the active agent is encapsulated in the liposomes. However, in the loading processes it can also happen that the active agent is also incorporated in the outer membrane that encloses the liposome or even on the outer surface of the liposomal membrane, so that the active agent, in this case, not only it is released from the inner part of the liposome but also from the liposome membrane or shell. The nature of the particulate carrier, especially the liposomes, is basically not critical to the drug delivery system of the present invention. All types of liposomes including negatively charged, neutral and cationic liposomes and the lipid complexes, as described in WO 96/27393, can be pressed into a highly compacted medicament material of the invention. Liposomes as described in our previous application, currently EP 0 639 373 can be used in the practice of this invention.
P1167 Preferably, the liposomes which are associated with at least one active agent are combined with at least one auxiliary material, such as a filler. Preferably, the auxiliary material is a pharmaceutically acceptable filler selected from, for example, sugars or physiologically acceptable salts. Particularly preferred are the auxiliary materials selected from lactose, trehalose, glucose, mannit, sodium chloride and combinations thereof. As an auxiliary material it is preferred to use lactose in a proportion of at least one hundred parts by weight of lactose to one part by weight of liposome. In a preferred embodiment, the drug material of the drug delivery system of the invention is compacted by isostatic pressing at pressures from 50 to 500 MPa. The at least one active agent can basically be any agent that shows pharmaceutical or biological effects ranging from, for example, small molecules to artificial human chromosomes, as long as these can be charged or associated with the liposomes. In particular, the at least one effective agent is selected from the group comprising: - ß2-sympathomimetics having a short-term effect such as salbutamol, terbutalin, fenoterol, bambuterol, - ß2-sympathomimetics which have such a long-lasting effect such as salmeterol, formoterol, - corticosteroids for inhalation purposes, such as budesonide, beclomethasone, fluticasone, - anticholinergic agents, such as ipatropium bromide, oxitropium bromide, - non-steroidal antiallergic agents, such as DSCG, nedocromile, - anti-aging agents. inflammatories, especially antibiotics and / or antiseptics, such as povidone iodine and combinations thereof. In addition, the at least one active agent of the drug material of the drug delivery system of the present invention can be selected from: - β-lactam antibiotics such as penicillins, cephalosporins, imipinem, aminoglycosides such as tobramycin, gentamicin; gyrase inhibitors, such as ofloxacin, ciproflaxin, antiviral agents, such as ganciclovir, azidothymidine, antimyotonic agents, such as polymeme, azole,
- vaccines against mumps, German mumps, diphtheria, whooping cough, polio and the like, - vaccines consisting essentially of viral or bacterial components,
P1167 - vaccines containing DNA encoding the generation of specific antigens, - opioids for pain relief and therapy, such as morphine, oxycodone, hydromorphine, buprenorphine, fentanyl, alfentanil, sulfentanil, and the like, - anti-infective agents, such as oligo / polirribo and / or oligo / polyidesoxy-ribonucleic acids,
- peptides, polypeptides, such as insulin, high and low molecular heparin, - hormones such as growth factors, hormones of the thyroid gland, sex hormones, calcitonin, and combinations thereof. Unless additional precautions are taken, the invention may be less suitable for hygroscopic agents, for agents that oxidize easily and for some unstable agents when exposed to light. However, it is often possible to add suitable protective substances to the amphiphiles that form the liposome membrane, to the internal substances of the liposome and / or to the auxiliary substances or carriers, to protect and sufficiently stabilize even the sensitive agents, to use them with this invention. In order to generate the particulate material from the highly compacted medicament material of the invention, any method for the generation of powder from a solid precursor can be used. Particularly preferred methods are those such as micronization or abrasion methods, especially those disclosed in EP 0 407 028 (incorporated by reference), as well as those of WO 94/14490 (incorporated by reference). The particles that are generated from the highly compacted medicament material preferably have particle sizes of from 0.1 to 50 μm, more preferably from 1 to 8 μm when used in pulmonary applications. The respective particle sizes are preferably 1 to 15 μm when used in nasal applications. The method of preparing the medicament material to be used in the drug delivery system, in accordance with the invention, comprises the steps of preparing the particulate carrier, especially the liposomes and the charge in a manner known per se. Optionally, the charged carrier particles are mixed with at least one auxiliary material and subsequently shaped into the body by isostatic pressing. Preferably, the applied pressure is in the range of from 50 to 500 MPa. The shaped body is preferably shaped to
P1167 which is used with the device as disclosed in WO 93/24165. This is especially a ring tablet, as disclosed in WO 94/14490. When the carrier is a liposomal material, a dry lipid film of, for example, phosphatidyl choline and phosphatidyl glycerol can be dispersed, for example, in an aqueous solution, preferably in a physiological solution. The respective active agent is present in the same solution as (optionally) the auxiliary material. The dispersion is treated by intimately mixing the ingredients by, for example, shaking. Then, the dispersion is subjected to one or more freeze-thaw cycles and emulsified, preferably by extrusion through a membrane. The freeze-thaw and emulsification cycles are repeated several times. In order to remove the non-encapsulated active agent, methods are used for the separation of liposomes and the active drug. These methods are known to those skilled in the art and are selected depending on the size of the active agent to be encapsulated. If, for example, a low molecular weight active agent has to be separated from the liposome dispersion, this can be done by dialyzing the sample. The final dispersion is further processed, in addition, for example, by
P1167 freezing and freeze drying. The solid material prepared preferably by lyophilization was ground to provide a coarse granulated liposome. This granulate is mixed with the auxiliary material and subsequently compressed at pressures between 50 and 500 MPa. With these methods, solid and non-brittle tablets having a smooth surface are obtained. The highly compacted solid drug material that will be used in the drug delivery system of the invention is useful for the generation of particles that can be administered by insufflation and / or inhalation. The highly compacted solid drug can be used in the conventional therapy of diseases and disorders of the respiratory tract as well as in diseases and disorders of organs. The medicament material of the invention can also be used in gene therapy and / or vaccination. Gene therapy is emerging as a clinically viable therapeutic regimen for genetic diseases, neoplastic and infectious. An important example is cystic fibrosis, a genetic disease that results from the immunization of the transmembrane conductance regulatory gene of cystic fibrosis (CFTR). Because of this, the pulmonary supply of liposomal carriers of gene constructs has recently received much attention. However, experimentally it has been shown that the repeated cyclization of DNA with or without liposomes, by means of a conventional nebulizer, is detrimental to DNA and leads to complete degradation within a few minutes after the start of nebulization. In addition to these, and in view of other general stability considerations related to the liposome, gene therapy requires that relatively concentrated doses of DNA or encapsulated DNA complexes be delivered within liposomes. However, concentrated solutions of DNA / lipid complexes tend to aggregate and precipitate, thereby rendering the dispersion of aqueous dispersions impractical. The drug delivery system of the present invention utilizing the highly compacted medicament material of the invention can, however, overcome the drawbacks of other methods of DNA / liposome administration, as is known in the prior art. Other targets of gene therapy may be the healing of deficiencies in factor IX and in the oci-antitrypsin gene, as well as the treatment of hemophilia, which is related to deficiencies in the production of factor VIII or in the production of other important proteins in the blood coagulation cascade. Of course, it must be understood that the objectives
P1167 mentioned above of gene therapy are mentioned for illustrative purposes only. They are not intended to limit the scope of the invention. Also, vaccination can be effected by the provision of the respective structures or substances with the drug delivery system of the present invention, in this case, conventional vehicles for inducing an immune response can be administered by carriers, such as the liposomes that they are present in the highly compacted medicament material of the invention. The following examples are intended to explain the invention in greater detail and are not intended to restrict or limit the scope of the invention.
EXAMPLE I A dry lipid film consisting of 5.76 grams of phosphatidylcholine and 0.64 grams of phosphatidylglycerol was dispersed in 160 ml of phosphate buffered saline (PBS) containing 3.8 grams of fluorescein isothiocyanate-dextran (FITC). dextran) and 28.8 grams of alpha-lactose. The dispersion was stirred manually for 2 hours, then subjected to freeze-thaw cycles and emulsified by extrusion through membranes with 100 nm pore size (Poretic) for 10 minutes at no more than 3,000 psi using an EmulsiFex homogenizer. -C5 (Avestin). The freeze-thaw and extrusion cycle was repeated three times. In order to eliminate FITC-dextran, not encapsulated, the liposome dispersion was dialyzed against a lactose solution (1,800 grams of alpha-lactose / 10 L of PBS) using a hollow fiber cartridge with a cut in the molecular weight of 18,000 at a rate of 8 to 10 ml / min. After three cycles of dialysis, the fluorescence concentration remained constant at approximately 50% of the original concentration as measured with a Hitachi F-2000 fluorescence spectrophotometer. The final dispersion was frozen in a mixture of dry ice and ethanol and transferred to a lyophilizer (Edwards Supermodulyo). The frozen preparation was dried by freezing at -40 ° C and 0.07 mbar for 48 hours, followed by a secondary drying at 25 ° C for 4 hours. The vacuum was replaced with dry nitrogen. The yield was 41.7 grams. The lyophilized cake was ground to provide a coarse granulate of free flowing liposome. This granulate was mixed at a ratio of 1:10 w / w with lactose being compressed isostatically at 150 Npa for about 60 seconds. Solid non-brittle tablets with a smooth surface were produced, mounted
P1167 on the plastic support of the device, in accordance with WO 93/24165 and stored at room temperature in a plastic container. It was acted 20 times on the tablets. The total scraped or shaved mass of the tablet surface was determined by each drive and the FITC-dextran content per drive. A total supplied mass of 9.66 +/- 0.99 mg containing 208 +/- 63 F.U was found. of FITC-dextran.
Example II The above procedure was repeated using liposomes prepared in accordance with EP 0 639 373, as follows: In a 1000 ml glass flask, provided with glass beads to increase the surface, 51.9 mg of cholesterol and 213 mg were dissolved of hydrogenated soy lecithin in a sufficient quantity of a mixture of methanol and chloroform in a ratio of 2: 1. The solvent was then evaporated in vacuo until a film formed on the inner surface of the flask and on the glass beads. In separate form 2.4 g of iodine-PVP (containing about 10% available iodine) were dissolved in 12 ml of water. Again, in a separate container,
P1167 dissolved 8.77 g of sodium chloride and 1.78 g Na2HP04 »2H20 in 400 ml of water. Additional water was added to a total volume of 980 ml and then approximately 12 ml of IN hydrochloric acid was added to adjust the pH to 7.4. This solution was then topped with water to exactly 1000 ml. In a fourth vessel, 900 mg of sucrose and 57 mg of disodium succinate were dissolved in 12 ml of water. The iodine-PVP solution was then added to the lipid film in the flask and the mixture was stirred until the film dissolved. This produced the formation of liposome from the hydrated lipids of the flask. The product was centrifuged and the supernatant liquid discarded. Up to 12 ml of the sucrose solution was added and the product was centrifuged again. After that, the supernatant liquid was discarded again. In this stage, an additional washing step could be used, using the. Sucrose solution or the sodium chloride buffer solution. After the last step of centrifugation and discarding the supernatant, up to 12 ml of buffered sodium chloride solution was added and the liposomes were homogeneously distributed therein. The product was then distributed in vial flasks which each contained 2 ml of the liposome dispersion and the
P1167 vials were then subjected to a freeze drying step. After freeze drying, each vial contained approximately 40 mg of solids. The solid liposomes were then compacted with lactose, as described in Example I. Ring tablets were used with the abrasion device of WO 93/24165 and a total of about 10 mg of powder was supplied per actuation. The content of iodine-PVP in the powder corresponded to the theoretical value (calculated), within the margin of experimental error.
P1167
Claims (14)
- CLAIMS! A drug delivery system comprising a highly compacted solid medicament material having an essentially isotropic solid state structure, comprising an active agent and this material is suitable for the generation of inhalable particles containing the active agent, wherein the highly compacted solid medicament material comprises at least one active agent that is associated with liposomes or a similar particulate carrier.
- 2. The drug delivery system according to claim 1, wherein the at least one active agent comprised in the highly compacted medicament material is encapsulated in the liposomes and / or associated with the membranes thereof.
- 3. The drug delivery system according to claim 1 and / or 2, wherein the highly compacted solid medicament material contains the liposomes together with auxiliary material, such as, filler materials.
- 4. The drug delivery system according to any of claims 1 to 3, wherein the at least one active agent comprised in the highly compacted solid medicament material is selected from the group comprising: - β2-sympathomimetics having an effect short P1167 duration such as salbutamol, terbutalin, fenoterol, bambuterol, - ß2-sympathomimetics having a long-lasting effect such as salmeterol, formoterol, - corticosteroids for inhalation purposes, such as budesonide, beclomethasone, fluticasone, - anticholinergic agents, such as ipatropium bromide, oxitropium bromide, non-steroidal antiallergic agents, such as DSCG, nedocromile, anti-inflammatory agents, especially antibiotics and / or antiseptics, such as povidone iodine and combinations thereof.
- The drug delivery system according to any of claims 1 to 3, wherein the at least one active agent comprised in the highly compacted solid drug material is selected from the group comprising: - β-lactam antibiotics such as penicillins , cephalosporins, imipinem, aminoglycosides such as tobramycin, gentamicin; gyrase inhibitors, such as ofloxacin, ciproflaxin, antiviral agents, such as ganciclovir, azidothymidine, antifungal agents, such as polymeme, azole, P1167 - vaccines against mumps, German mumps, diphtheria, whooping cough, polio and the like, - vaccines consisting essentially of viral or bacterial components, - vaccines containing DNA that codes for the generation of specific antigens, - opioids for relief and therapy of pain, such as morphine, oxycodone, hydromorphine, buprenorphine, fentanyl, alfentanil, sulfentanil, and the like, - anti-infective agents, such as oligo / polirribo and / or oligo / polydeoxy-ribonucleic acids, - peptides, polypeptides, such as insulin, high and low molecular heparin, - hormones such as growth factors, hormones of the thyroid gland, sex hormones, calcitonin, and combinations thereof.
- 6. The drug delivery system according to any of claims 1 to 5, wherein the highly compacted solid medicament material has been compacted by isostatic pressing at pressures from 50 to 500 MPa.
- 7. The drug delivery system according to any of claims 1 to 6, wherein the auxiliary material in the solid drug material is very Compacted P1167 is selected from lactose, trehalose, glucose, mannitol, sodium chloride and combinations thereof.
- 8. The drug delivery system according to any of claims 1 to 7, wherein the liposomes are mixed with lactose in a ratio of at least one hundred parts by weight of lactose to one part by weight of liposome.
- The drug delivery system according to any of claims 1 to 5, wherein the highly compacted medicament material is subjected to the appropriate processes to generate particles, such as, for example, micronization or abrasion.
- The drug delivery system according to claim 9, wherein the particles generated have particle sizes ranging from 0.1 to 50 μm, in particular from 1 to 8 μm when used in lung applications and from 1 to 15 μg when They are used in nasal applications.
- The drug delivery system according to claim 1, wherein the particulate carrier is selected from microspheres, nanoparticles, large porous particles, artificial viral envelopes, and similar pharmaceutically acceptable materials.
- 12. A method for the preparation of the highly compacted solid drug material of the P1167 drug delivery of any of claims 1 to 11, wherein the liposomes which are prepared or charged in a known manner, are optionally mixed with at least one auxiliary material and subsequently shaped into a shaped body by isostatic pressing.
- The method according to claim 12, wherein the isostatic pressing is carried out at pressures from 50 to 5000 MPa.
- 14. The use of a highly compacted solid medicament material in a drug delivery system according to claims 1 to 11 for the generation of particles that can be administered by insufflation and / or inhalation, in the therapy of diseases and disorders of the respiratory tract, as well as diseases and organ disorders, gene therapy and / or vaccination. P1167
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US60/086,895 | 1998-05-27 |
Publications (1)
Publication Number | Publication Date |
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MXPA00011650A true MXPA00011650A (en) | 2002-07-25 |
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