1. A process for the preparation of an agglomerated solid dosage form, comprising
(1) preparing an aqueous slurry of
(a) microcrystalline cellulose;
(b) a microcrystalline cellulose compressibility augmenting agent which
(I) physically restricts the proximity of the interface between adjacent cellulose surfaces;
(ii) inhibits interactions between adjacent cellulose surfaces, via the creation of a hydrophobic boundary at cellulose surfaces; or
(iii) accomplishes both (I) and (ii) above;
(c) an active agent; and
(d) an effective amount of a sustained release carrier;
(2) thereafter spray drying the resultant aqueous slurry in a manner which inhibits quasi-hornification, thereby obtaining agglomerated particles which are directly compressible into a solid sustained release matrix which provides release of the active agent over a time period of about 8 to about 24 hours.
2. The process of claim 1, further comprising compressing the agglomerated particles into a tablet.
3. The process of claim 1, wherein said compressibility augmenting agent is a surfactant having an HLB of at least about 10.
4. The process of claim 1, wherein said compressibility augmenting agent is a surfactant having an HLB of at least about 15.
5. The process of claim 1, wherein said compressibility augmenting agent is a surfactant having an HLB from about 15 to about 40.
6. The process of claim 5, wherein said compressibility augmenting agent is sodium lauryl sulfate.
7. The process of claim 5, wherein said compressibility augmenting agent is a polysorbate.
8. The process of claim 1, wherein said compressibility augmenting agent further comprises a silicon dioxide having an average primary particle size from about 1 nm to about 100 \u03bcm.
9. The process of claim 8, wherein said silicon dioxide is included in amount from about 0.1% to about 20% by weight, based on the weight of microcrystalline cellulose.
10. The process of claim 3, wherein said surfactant is included in amount from about 0.1% to about 20% by weight, based on the weight of microcrystalline cellulose.
11. The process of claim 9, wherein said silicon dioxide is colloidal silicon dioxide.
12. The process of claim 1, wherein said sustained release carrier is selected from the group consisting of an alkyl cellulose, an acrylic polymer or copolymer, a cellulose ether, a cellulose ester, and mixtures thereof.
13. The process of claim 1, wherein said sustained release carrier is selected from natural or a synthetic gums.
14. The process of claim 1, further comprising adding a film forming agent into the aqueous slurry, and drying the aqueous slurry in such a manner as to obtain agglomerated particles having a film coating.
15. The process of claim 14, further comprising compressing the agglomerated particles into tablets.
16. The process according to claim 1, wherein the aqueous slurry has a solids content from about 0.5 to about 25%, by weight prior to said spray drying step.
17. The process according to claim 1, wherein the aqueous slurry has a solids content from about 15 to about 20%, by weight prior to said spray drying step.
18. The product according to claim 1.
19. The process of claim 1, further comprising admixing a further amount of sustained release carrier with said agglomerated particles and compressing the resulting mixture into tablets.
20. The process of claim 19, further comprising wet granulating said mixture, and then compressing the resulting mixture into tablets.
21. The process of claim 19, further comprising adding a further amount of active ingredient to the mixture.
22. The process of claim 1, further comprising adding a pharmaceutically acceptable filler to the aqueous slurry.
23. The process of claim 22, wherein the pharmaceutically acceptable filler is selected from the group consisting of a monosaccharide, a dissacharide, a polyhydric alcohol, inorganic phosphates, sulfates, carbonates and mixtures thereof.
24. The process of claim 22, wherein the pharmaceutically acceptable filler is selected from the group consisting of sucrose, dextrose, lactose, xylitol, fructose, sorbitol, calcium phosphate, calcium sulfate, calcium carbonate, \u201coff-shelf\u201d microcrystalline cellulose and mixtures thereof.
25. The process of claim 1, wherein said sustained release carrier includes a release modifying agent that alters the release rate of the active agent from the formulation upon exposure to an aqueous medium.
26. The process of claim 25, wherein said release modifying agent is selected from the group consisting of calcium sulfate, sodium chloride, potassium sulfate, sodium bicarbonate, lithium chloride, tripotassium phosphate, sodium borate, potassium bromide, potassium fluoride, sodium bicarbonate, calcium chloride, magnesium chloride, sodium citrate, sodium acetate, calcium lactate, magnesium sulfate and sodium fluoride.
27. The process of claim 1, wherein the slurry includes a plurality of slurries, each of the plurality of slurries containing one of: a) a microcrystalline cellulose; or ii) a microcrystalline cellulose compressibility augmenting agent.
28. The process of claim 1, wherein said sustained release carrier is selected from the group consisting of a polylactide, a polyglycolide, a poly(lactide-co-glycolide), a polyanhydride, a polyorthoester, polycaprolactones, polyphosphazenes, polysaccharidcs, proteinaceous polymers, soluble derivatives of polysaccharides, soluble derivatives of proteinaceous polymers, polypeptides, polyesters and polyorthoesters.
29. A process for the preparation of a sustained release agglomerated solid dosage form, comprising
(1) preparing an aqueous slurry of
(a) microcrystalline cellulose;
(b) a microcrystalline cellulose compressibility augmenting agent comprising:
(i) silicon dioxide; or
(ii) a surfactant selected from the group consisting of sodium lauryl sulfate, docusate salts, alkyl carboxylates, acyl lactylates, alkyl ether carboxylates, N-acyl sarcosinates, polyvalent alkyl carbonates, N-acyl glutamates, fatty acids, polypeptide condensates sulfuric acid esters, polyoxyethylene compounds, lecithin, ethoxylated alcohols, ethoxylated esters, ethoxylated amides, polyoxypropylene compounds, propoxylated alcohols, ethoxylatedpropoxylated block polymers, propoxylated esters, alkanolamides, amine oxides, fatty acid esters of polyhydric alcohols, ethylene glycol esters, diethylene glycol esters, propylene glycol esters, glycerol esters, polyglycerol fatty acid esters, sorbitan esters, sucrose esters, glucose esters, simethicone, acacia, benzalkonium chloride, cholesterol, emulsifying wax, glycerol monostearate, lanolin alcohols, lecithin, poloxamer, polyoxyethylene and castor oil derivatives; or
(iii) a highly polar dye selected from the group consisting of 3,3\u2032-1,1\u2032Biphenyl-4,4\u2032-diylbis-(azo)bis4-amino-1-naphthalenesulfonic acid disodium salt; disodium salt of 6-hydroxy-5(2-4-sulfophenyl) azo-2-naphthalenesulfonic acid); 5-oxo-1-(p-sulfophenyl)-4sulfophenyl)azo-2-pyrazoline-3-carboxylic acid, trisodium salt); disodium salt of 1-p-sulphophenylazo-2-naphthol-6-sulfonic acid); trisodium-2-hydroxy-1-(4-sulfonato-1-naphthylazo) naphthalene-6, 8-disulfonate); disodium 4,4\u2032-(2,4-dihydroxy-5-hydroxymethyl-3, 3-phenylene bisazo)di(napthalene-1-sulfonate)); tetrasodium 4-acetamido-5-hyroxy-6-7-sulfonato-4-(4-sulfonatopheylazo)-1-naphthylazonaphthalene-1,7-disulfonate); disodium 4-hydroxy-3-(4-sulfanato-1-naphythylazo) Naphthalene-1-sulfonate); trisodluin 2-hydroxy-1-(4-sulfonato-1-naphthylazo) naphthalene-3,6-disulfonate) and mixtures thereof; or
(iv) a combination of two ro more of (I), (ii) and (iii) above;
(c) an active agent; and
(d) an effective amount of a sustained release carrier; and
(2) thereafter spray drying the resultant aqueous slurry in a manner which inhibits quasi-hornification, thereby obtaining agglomerated particles which are directly compressible into a solid sustained release matrix which provides release of the active agent over a time period of about 8 to about 24 hours.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A transmission apparatus, comprising:
an amplifier controller configured to determine a target value for an average optical input power of a transmitting amplifier in a transmitting-side apparatus of the transmission apparatus, based on an index based on a quality of transmission from an output of the transmitting amplifier to a receiving amplifier in a receiving-side apparatus of another transmission apparatus; and
a pre-emphasis controller configured to determine amounts of adjustment of transmission optical powers for respective wavelengths, based on the target value and per-wavelength reception optical powers at the receiving amplifier.
2. The transmission apparatus according to claim 1,
wherein the amplifier controller calculates an amount of tilt based on the per-wavelength reception optical powers at the receiving amplifier, and when the amount of tilt is larger than a present pre-emphasis controllable amount, the amplifier controller sets the target value to a smaller value than a present average optical input power of the transmitting amplifier.
3. The transmission apparatus according to claim 1, further comprising:
an amplified spontaneous emission (ASE) calculator configured to calculate a cumulative ASE from the output of the transmitting amplifier to the receiving amplifier in the receiving-side apparatus; and
an optical signal-to-noise ratio (OSNR) calculator configured to calculate an OSNR from the output of the transmitting amplifier to the receiving amplifier in the receiving-side apparatus, based on the cumulative ASE,
wherein the amplifier controller uses the OSNR as the index.
4. The transmission apparatus according to claim 3,
wherein each of the transmitting-side apparatus of the transmission apparatus, the receiving-side apparatus of the another transmission apparatus, and a relay apparatus placed therebetween adds an ASE calculated by the each apparatus to an ASE received from a corresponding upstream apparatus and transfers a resulting ASE to a downstream apparatus, and the ASE calculator uses, as the cumulative ASE, an ASE transferred from the receiving-side apparatus.
5. The transmission apparatus according to claim 3,
wherein each of the transmitting-side apparatus of the transmission apparatus, the receiving-side apparatus of the another transmission apparatus, and a relay apparatus placed therebetween adds an ASE calculated by the each apparatus to an ASE received from a corresponding downstream apparatus and transfers a resulting ASE to a corresponding upstream apparatus, and the ASE calculator uses, as the cumulative ASE, an ASE transferred from an upstream apparatus immediately preceding the transmission apparatus.
6. The transmission apparatus according to claim 3,
wherein a network monitoring system adds ASEs calculated by the transmission apparatus, the receiving-side apparatus, and a relay apparatus placed therebetween and reports a resulting ASE to the ASE calculator, and the ASE calculator uses, as the cumulative ASE, the ASE reported from the network monitoring system.
7. The transmission apparatus according to claim 1, further comprising a span-loss calculator configured to calculate a total span loss by adding span losses from the output of the transmitting amplifier to the receiving amplifier in the receiving-side apparatus,
wherein the amplifier controller uses the total span loss as the index.
8. A transmission system, comprising:
a transmitting-side apparatus, a receiving-side apparatus, and one or more relay apparatuses placed therebetween, the receiving-side apparatus monitoring per-wavelength reception optical powers at a receiving amplifier in the receiving-side apparatus and reporting the per-wavelength reception optical powers to the transmitting-side apparatus, and
the transmitting-side apparatus including:
an amplifier controller configured to determine a target value for an average optical input power of a transmitting amplifier, based on an index based on a quality of transmission from an output of the transmitting amplifier to the receiving amplifier in the receiving-side apparatus; and
a pre-emphasis controller configured to determine amounts of adjustment of transmission optical powers for respective wavelengths, based on the target value and per-wavelength reception optical powers at the receiving amplifier.
9. The transmission system according to claim 8, wherein
the amplifier controller calculates an amount of tilt based on the per-wavelength reception optical powers at the receiving amplifier, and when the amount of tilt is larger than a present pre-emphasis controllable amount, the amplifier controller sets the target value to a smaller value than a present average optical input power of the transmitting amplifier.
10. The transmission system according to claim 8, further comprising:
an amplified spontaneous emission (ASE) calculator configured to calculate a cumulative ASE from the output of the transmitting amplifier to the receiving amplifier in the receiving-side apparatus; and
an optical signal-to-noise ratio (OSNR) calculator configured to calculate an OSNR from the output of the transmitting amplifier to the receiving amplifier in the receiving-side apparatus, based on the cumulative ASE,
wherein the amplifier controller uses the OSNR as the index.
11. The transmission system according to claim 10, wherein
each of the transmitting-side apparatus, the receiving-side apparatus, and the relay apparatus adds an ASE obtained by the each apparatus to an ASE received from a corresponding upstream apparatus and transfers a resulting ASE to a corresponding downstream apparatus, and the transmitting-side apparatus uses, as the cumulative ASE, an ASE transferred from the receiving-side apparatus.
12. The transmission system according to claim 10, wherein
each of the transmitting-side apparatus, the receiving-side apparatus, and the relay apparatus adds an ASE obtained by the each apparatus to an ASE received from a corresponding downstream apparatus and transfers a resulting ASE to a corresponding upstream apparatus, and the transmitting-side apparatus uses, as the cumulative ASE, an ASE transferred from an upstream apparatus immediately preceding the transmitting-side apparatus.
13. The transmission system according to claim 10, further comprising a network monitoring system, wherein
the transmission apparatus, the receiving-side apparatus, and the relay apparatus reports ASEs calculated by the respective apparatuses to the network monitoring system,
the network monitoring system adds the reported ASEs and reports a resulting ASE to the ASE calculator in the transmitting-side apparatus, and
the ASE calculator uses, as the cumulative ASE, the ASE reported from the network monitoring system.
14. The transmission system according to claim 8, wherein
the transmitting-side apparatus further comprises a span-loss calculator configured to calculate a total span loss by adding span losses from the output of the transmitting amplifier to the receiving amplifier in the receiving-side apparatus, and
the amplifier controller uses the total span loss as the index.
15. A method of controlling average optical input power of a transmitting amplifier in a transmission apparatus, the method comprising:
determining, by an amplifier controller in the transmission apparatus, a target value for an average optical input power of the transmitting amplifier, based on an index based on a quality of transmission from an output of the transmitting amplifier to a receiving amplifier in a receiving-side apparatus; and
determining amounts of adjustment of transmission optical powers for respective wavelengths, based on the target value and per-wavelength reception optical powers at the receiving amplifier.
16. The method according to claim 15, wherein,
in the determining the target value, the amplifier controller sets the target value to a smaller value than a present average optical input power, as the quality of transmission indicated by the index decreases.
17. The method according to claim 15, wherein
an amplified spontaneous emission (ASE) calculator in the transmission apparatus calculates a cumulative ASE from the output of the transmitting amplifier to the receiving amplifier in the receiving-side apparatus;
an optical signal-to-noise ratio (OSNR) calculator in the transmission apparatus calculates an OSNR from the output of the transmitting amplifier to the receiving amplifier in the receiving-side apparatus, based on the cumulative ASE; and
the amplifier controller uses the OSNR as the index.
18. The method according to claim 17, wherein
each of the transmission apparatus, the receiving-side apparatus, and a relay apparatus placed therebetween adds an ASE obtained by the each apparatus to an ASE received from a corresponding upstream apparatus and transfers a resulting ASE to a corresponding downstream apparatus, and
the ASE calculator uses, as the cumulative ASE, an ASE transferred from the receiving-side apparatus.
19. The method according to claim 17, wherein
each of the transmission apparatus, the receiving-side apparatus, and a relay apparatus placed therebetween adds an ASE obtained by the each apparatus to an ASE received from a corresponding downstream apparatus and transfers a resulting ASE to a corresponding upstream apparatus; and
the ASE calculator uses, as the cumulative ASE, an ASE transferred from an upstream apparatus immediately preceding the transmission apparatus.
20. The method according to claim 17, wherein
a network monitoring system adds ASEs calculated by the transmission apparatus, the receiving-side apparatus, and a relay apparatus placed therebetween and reports a resulting ASE to the ASE calculator; and
the ASE calculator uses, as the cumulative ASE, the ASE reported from the network monitoring system.