SOLID CARRIERS FOR IMPROVED DELIVERY OF ACTIVE INGREDIENTS IN PHARMACEUTICAL COMPOSITIONS

• US 20090074859A1
• Filed: 12/02/2008
• Published: 03/19/2009
• Est. Priority Date: 11/23/1999
• Status: Abandoned Application

• Current Assignee: Lipocine Inc.
• Original Assignee: Lipocine Inc.
• Inventors: Patel, Mahesh
• Application Number:
  US12/326,711
• Publication Number:
  US 20090074859A1
• Time in Patent Office: Days
• US Class Current: 424/457
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/5383 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 17/12 Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 19/06 : Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/10 : for osteoporosis
• CPC Class Codes: A61P 21/02 : Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 : Anxiolytics
• CPC Class Codes: A61P 25/26 : Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 33/10 : Anthelmintics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/16 : for decreasing, blocking or antagonising the activity of the thyroid hormones
• CPC Class Codes: A61P 5/24 : of the sex hormones
• CPC Class Codes: A61P 5/40 : Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10S 977/906 : Drug delivery
• CPC Class Codes: Y10S 977/927 : Diagnostic contrast agent

Abstract

The present invention provides solid pharmaceutical compositions for improved delivery of a wide variety of pharmaceutical active ingredients contained therein or separately administered. In one embodiment, the solid pharmaceutical composition includes a solid carrier, the solid carrier including a substrate and an encapsulation coat on the substrate. The encapsulation coat can include different combinations of pharmaceutical active ingredients, hydrophilic surfactant, lipophilic surfactants and triglycerides. In another embodiment, the solid pharmaceutical composition includes a solid carrier, the solid carrier being formed of different combinations of pharmaceutical active ingredients, hydrophilic surfactants, lipophilic surfactants and triglycerides. The compositions of the present invention can be used for improved delivery of hydrophilic or hydrophobic pharmaceutical active ingredients, such as drugs, nutritional agents, cosmeceuticals and diagnostic agents.

Claims

1. A pharmaceutical composition in the form of a solid carrier, said composition comprising,

at least two components selected from the group consisting of a pharmaceutical active ingredient;

a hydrophilic surfactant, and a lipophilic component,

wherein the pharmaceutical active ingredient is selected from the group consisting of testosterone undecanoate, ziprasidone, clozapine, cilostazol, clonazepam, dronabinol, clarithromycin, levofloxacin, and their pharmaceutically acceptable salts, isomers, analogs, and derivatives.

2. The pharmaceutical composition of claim 1, wherein the composition includes a hydrophilic surfactant and the hydrophilic surfactant is ionic or non-ionic.

3. The pharmaceutical composition of claim 1, wherein the composition includes a hydrophilic surfactant having an HLB value of at least 10.

4. The pharmaceutical composition of claim 1, wherein the composition includes a hydrophilic surfactant selected from the group consisting of lauryl macrogolglycerides;

polyethylene glycol fatty acids esters;

polyethylene glycol glycerol fatty acid esters;

polyoxyethylene sorbitan fatty acid esters;

polyoxyethylene-polyoxypropylene block copolymers;

polyglycerol fatty acid esters;

polyoxyethylene glycerides;

polyoxyethylene vegetable oils;

polyoxyethylene hydrogenated vegetable oils;

reaction mixtures of polyols and at least one member of the group consisting of fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, and sterols;

tocopherol polyethylene glycol succinates;

sugar esters;

fatty acid derivatives of amino acids, carnitines, oligopeptides, and polypeptides;

glyceride derivatives of amino acids, oligopeptides, and polypeptides;

acyl lactylates;

mono-diacetylated tartaric acid esters of mono-diglycerides;

succinylated monoglycerides;

citric acid esters of mono-diglycerides;

alginate salts;

propylene glycol alginate;

lecithins and hydrogenated lecithins;

salts of alkylsulfates;

salts of fatty acids;

sodium docusate; and

mixtures thereof

5. The pharmaceutical composition of claim 2, wherein the hydrophilic surfactant is selected from the group consisting of polyethylene glycol fatty acids esters;

polyethylene glycol glycerol fatty acid esters;

polyoxyethylene sorbitan fatty acid esters;

polyoxyethylene-polyoxypropylene block copolymers;

polyglyceryl fatty acid esters;

polyoxyethylene glycerides;

polyoxyethylene vegetable oils;

polyoxyethylene hydrogenated vegetable oils; and

tocopherol polyethylene glycol succinates.

6. The pharmaceutical composition of claim 4, wherein the hydrophilic surfactant is selected from the group consisting of PEG-20 sorbitan monolaurate;

PEG-20 sorbitan monooleate;

polyglyceryl-10 laurate;

polyglyceryl-10 monooleate, polyglycerol-10 dioleate and mixtures thereof, polyglyceryl-10 stearate;

polyglyceryl-10 linoleate;

PEG-8 caprylic/capric glycerides;

PEG-40 hydrogenated castor oil;

PEG-35 castor oil; and

tocopheryl PEG-1000 succinate.

7. The pharmaceutical composition of claim 2, wherein the hydrophilic surfactant is selected from the group consisting of lecithin, lactylic esters of fatty acids, stearoyl lactylate, succinylated monoglycerides, monoacetylated and diacetylated tartaric acid esters of monoglycerides and diglycerides, citric acid esters of monoglycerides and diglycerides, taurocholate, caprylate, caprate, oleate, lauryl sulfate, docusate, and salts and mixtures thereof.

8. The pharmaceutical composition of claim 1, wherein the composition includes a hydrophilic surfactant and the hydrophilic surfactant represents 2.4% w/w to 76% w/w of the solid carrier.

9. The pharmaceutical composition of claim 1, wherein the composition includes hydrophilic surfactant and the hydrophilic surfactant 12.1% w/w to 76% w/w of the solid carrier.

10. The pharmaceutical composition of claim 1, wherein the composition is formulated for immediate release.

11. The pharmaceutical composition of claim 1, wherein the composition is formulated for pulsatile release, controlled release, extended release, delayed release, targeted release, or targeted delayed release.

12. The pharmaceutical composition of claim 1, is in the form of a capsule, a tablet, a granule, a pellet, or a bead.

13. The pharmaceutical composition of claim 12, wherein the lipophilic component is a lipophilic surfactant or a triglyceride.

14. The pharmaceutical composition of claim 1, wherein the composition includes a lipophilic component having an HLB value of less than 10.

15. The pharmaceutical composition of claim 12, wherein the lipophilic component is selected from the group consisting of triglycerides;

fatty acids;

lower alcohol fatty acid esters;

polyethylene glycol glycerol fatty acid esters;

polypropylene glycol fatty acid esters;

polyoxyethylene glycerides;

glycerol fatty acid esters;

acetylated glycerol fatty acid esters;

lactic acid derivatives of mono/diglycerides;

sorbitan fatty acid esters;

polyoxyethylene sorbitan fatty acid esters;

polyoxyethylene-polyoxypropylene block copolymers;

polyoxyethylene vegetable oils;

polyoxyethylene hydrogenated vegetable oils; and

reaction mixtures of polyols and fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, and sterols.

16. The pharmaceutical composition of claim 12, wherein the lipophilic component is selected from the group consisting of glyceryl laurate;

glyceryl stearate;

glyceryl monooleate;

glycerol monostearate;

glyceryl monostearate;

glycerol monolinoleate;

sorbitan monooleate;

sorbitan monolaurate;

polyglyceryl-2 oleate;

polyglyceryl-2 stearate;

polyglyceryl-2 isostearate;

polyglyceryl-3 oleate;

polyglyceryl-4 oleate;

polyglyceryl-4 stearate;

polyglyceryl-6 oleate;

polyglyceryl-3 dioleate;

polyglyceryl-3 distearate;

polyglyceryl-4 pentaoleate;

polyglyceryl-6 dioleate;

polyglyceryl-2 dioleate;

polyglyceryl-10 trioleate;

polyglyceryl-10 tetraoleate.

17. The pharmaceutical composition of claim 1, wherein the composition also includes an additive selected from the group consisting of natural or synthetic waxes and polymers.

18. The pharmaceutical composition of claim 17, wherein the additive is a selected from the group consisting of natural or synthetic waxes.

19. The pharmaceutical composition of claim 17, wherein the additive is a polymer.

20. The pharmaceutical composition of claim 19, wherein the polymer is selected from the group consisting of polyvinylpyrrolidone and cellulose derivatives.