FORMULATIONS AND METHODS FOR THE CONTROLLED RELEASE OF ACTIVE DRUG SUBSTANCES
Controlled release formulations and methods for preparing controlled release formulations for delivery of active drug substances are described herein. The formulations described herein may be employed to produce pharmaceutical compositions, such as controlled release dosage forms, adjusted to a specific administration scheme.
1 - 58 . (canceled)
59 . A tablet for oral delivery of an analgesic, the tablet comprising:
a) a matrix composition having a cylindrical shape with two ends, wherein each of the two ends is optionally tapered, the length of the matrix is shorter than 8 mm, the matrix composition comprises (i) an analgesic and (ii) at least one polyglycol, and the matrix composition exhibits a release rate of the analgesic from the matrix in ethanol that is equal to or lower than the release rate of the analgesic from the matrix in water; and
b) a coating substantially surrounding the matrix composition and having one or two openings exposing at least one surface of the matrix composition, the coating being substantially impermeable to an aqueous medium,
wherein the analgesic is selected from at least one of oxycodone and hydrocodone,
wherein the tablet provides controlled release of the analgesic over an interval of 5 to 20 hours, and
wherein the tablet is resistant to isolation of the analgesic by any of crushing of the tablet, melting of the tablet, and ethanol extraction.
60 . The tablet according to claim 59 , wherein the area of the cross section of the matrix is in the range of 1 to 75 mm 2 .
61 . The tablet according to claim 59 , wherein the area of the cross section of the matrix is at least 20 mm 2 .
62 . The tablet according to claim 59 , wherein the length of the matrix is selected from the group consisting of 4 to 8 mm, 5.5 to 8 mm, and 6 to 7.5 mm.
63 . The tablet according to claim 59 , wherein the tablet provides controlled release of the analgesic over an interval that is in a range selected from the group consisting of about 7 to 20 hours, about 6 to 18 hours, about 10 to 20 hours, about 10 to 18 hours, about 10 to 16 hours, about 10 to 14 hours, and about 11 to 13 hours.
64 . The tablet according to claim 59 , wherein the tablet provides controlled release of the analgesic over an interval of 12 hours.
65 . The tablet according to claim 59 , wherein the coating comprises two openings each exposing one end of the matrix.
66 . The tablet according to claim 59 , wherein a therapeutically effective response is achieved over the entire interval between administrations.
67 . The tablet according to claim 59 , wherein the tablet provides a steady state trough of the analgesic that is in a range selected from the group consisting of 5 to 40% of steady state C max , 5 to 30% of steady state C max , 10 to 30% of steady state C max , 10 to 20% of steady state C max , 14 to 27% of steady state C max , and 8 to 20% of steady state C max .
68 . The tablet according to claim 59 , wherein the tablet provides controlled release of the analgesic such that a 2 nd point where a plasma concentration of the analgesic of 50% of steady state C max is reached is in the range of 4 to 6 hours.
69 . The tablet according to claim 59 , wherein the tablet provides controlled release of the analgesic in a manner that results in a MRT that is in a range selected from the group consisting of 8 to 15 hours, 10 to 15 hours, and 11 to 14.5 hours.
70 . The tablet according to claim 59 , wherein the tablet provides controlled release of the analgesic in a manner that results in a T max in the range of 3 to 6 hours after last administration to a steady state individual.
71 . The tablet according to claim 59 , wherein the tablet provides a protraction index of at least 0.20.
72 . The tablet according to claim 59 , wherein the tablet delivers sufficient analgesic in a controlled manner over a 12-hour period to achieve pain relief over a 12-hour period.
73 . The tablet according to claim 59 , wherein each dosage of the analgesic is in the range of 10 to 500 mg.
74 . The tablet according to claim 59 , wherein the polyglycol is a water soluble crystalline or semi-crystalline polymer.
75 . The tablet according to claim 59 , comprising at least one polyglycol that is a homopolymer.
76 . The tablet according to claim 59 , comprising at least one polyglycol that is a copolymer.
77 . The tablet according to claim 59 , wherein the total concentration of the at least one polyglycol included in the matrix composition is selected from the group consisting of 5 to 99% w/w, 15 to 95% w/w, 30 to 90% w/w, 30 to 85% w/w, 30 to 80% w/w, 40 to 80% w/w, 45 to 75% w/w, 40 to 50% w/w, 45 to 50% w/w, 60 to 85% w/w, 60 to 80% w/w, and 70 to 75% w/w.
78 . The tablet according to claim 75 , wherein the at least one polyglycol is a polyethylene glycol and/or a polyethylene oxide.
79 . The tablet according to claim 76 , wherein the polyethylene glycol and/or polyethylene oxide has a molecular weight selected from the group consisting of 20,000 to 700,000 daltons, 20,000 to 600,000 daltons, 35,000 to 500,000 daltons, 35,000 to 400,000 daltons, 35,000 to 300,000 daltons, 50,000 to 300,000 daltons, 200,000 daltons, and 300,000 daltons.
80 . The tablet according to claim 76 , wherein the matrix comprises at least two different polyglycols, wherein the different polyglycols are selected from the group consisting of polyethylene oxides.
81 . The tablet according to claim 78 , wherein one polyethylene oxide has an average molecular weight in the range of 150,000 to 250,000 daltons and the other polyethylene oxide has an average molecular weight in the range of 250,000 to 350,000 daltons.
82 . The tablet according to claim 75 , wherein the concentration of homopolymer in the matrix composition is selected from the group consisting of 5 to 90% w/w, 20 to 85% w/w, 20 to 75% w/w, 20 to 70% w/w, 20 to 40% w/w, 30 to 85% w/w, 30 to 75% w/w, 30 to 50% w/w, 30 to 40% w/w, 30 to 35% w/w, 31 to 33% w/w, 50 to 85% w/w, 60 to 80% w/w, 70 to 80% w/w, 70 to 75% w/w, and 71 to 73% w/w.
83 . The tablet according to claim 73 , wherein the copolymer is a poloxamer that has an average molecular weight selected from the group consisting of 2,000 to 30,000 daltons, 2,000 daltons to 20,000 daltons, 4,000 daltons to 18,000 daltons, and
6,000 daltons to 10,000 daltons.
84 . The tablet according to claim 76 , wherein the matrix comprises one or more copolymers selected from the group consisting of poloxamers.
85 . The tablet according to claim 84 , wherein the matrix comprises only one poloxamer and has a length selected from the group consisting of 4 to 8 mm, 5.5 to 8 mm, and 6 to 7.5 mm.
86 . The tablet according to claim 76 , wherein the concentration of copolymer in the matrix composition is selected from the group consisting of 0 to 30% w/w, 1 to 20 w/w, 2 to 10% w/w, 2 to 5% w/w, 5 to 30% w/w, 5 to 20% w/w, and 5 to 15% w/w.
87 . The tablet according to claim 59 , wherein the coating is insoluble in an aqueous medium.
88 . The tablet according to claim 59 , wherein the coating comprises one or more polymers selected from the group consisting of starch based polymers, cellulose based polymers, synthetic polymers, and biodegradable polymers.
89 . The tablet according to claim 59 , wherein the coating comprises one or more polymers selected from the group consisting of ethyl cellulose grade 20, ethyl cellulose grade 100, polylactic acid (PLA), Cornpack 200, polycaprolactone, PEO 7000000, and polyhydroxybuturate.
90 . The tablet according to claim 59 , wherein the coating comprises an ethyl cellulose selected from an ethyl cellulose of grade 20 and an ethyl cellulose of grade 100.
91 . The tablet according to claim 59 , wherein the coating comprises one or more biodegradable polymers, selected from the group consisting of polylactic acid and polycaprolactone.
92 . The tablet according to claim 59 , wherein the coating comprises at least 85% polymers, and wherein the polymers are selected from the group consisting of biodegradable polymers and cellulose based polymers.
93 . The tablet according to claim 59 , wherein the coating comprises one or more plasticizers.
94 . The tablet according to claim 59 , wherein the tablet is formed by injection molding or extrusion.