Oral formulations of pyrrolidine derivatives
The present invention relates to solid oral formulations comprising a compound of formula (3Z,5S)-5-(hydroxymethyl)-1-[(2′-methyl-1,1′-biphenyl-4-yl)carbonyl]pyrrolidin-3-one O-methyloxime, and/or an active metabolite thereof, and the use of said formulations in the treatment and/or prevention of preterm labor, premature birth, dysmenorrhea and embryo implantation failure due to uterine contractions. The present invention is furthermore related to processes for their preparation.
1. A dispersible tablet comprising a compound of formula (3Z,5S)-5-(hydroxymethyl)-1-[(2′-methyl-1,1′-biphenyl-4-yl)carbonyl]pyrrolidin-3-one-O-methyloxime in substantially pure form, wherein the dispersible tablet has the following composition:
20% by weight of the compound of formula (3Z,5S)-5-(hydroxymethyl)-1-[(2′-methyl-1,1′-biphenyl-4-yl)carbonyl]pyrrolidin-3-one-O-methyloxime;
1-20% by weight of calcium silicate;
0.1-20% by weight of polyvinylpyrrolidone (PVP) 30K;
0.01-5% by weight of poloxamer 188;
0.5-20% by weight of sodium croscarmellose;
1-90% by weight of microcrystalline cellulose 112;
1-90% by weight of lactose monohydrate;
0.01-0.5% by weight of sodium saccharine; and
0.1-10% by weight of glycerol dibehenate.
2. The dispersible tablet of claim 1 , wherein the dispersible tablet comprises from about 10 mg to about 500 mg of the compound of formula (3Z,5S)-5-(hydroxymethyl)-1-[(2′-methyl-1,1′-biphenyl-4-yl)carbonyl]pyrrolidin-3-one-O-methyloxime.
3. The dispersible tablet of claim 1 , consisting essentially of:
20% by weight of the compound of formula (3Z,5S)-5-(hydroxymethyl)-1-[(2′-methyl-1,1′-biphenyl-4-yl)carbonyl]pyrrolidin-3-one-O-methyloxime;
5% by weight of calcium silicate;
1% by weight of PVP30K;
2% by weight of poloxamer 188;
5% by weight of sodium croscarmellose;
15% by weight of microcrystalline cellulose 112;
47.8% by weight of lactose monohydrate;
0.2% by weight of sodium saccharine; and
4% by weight of glycerol dibehenate.
4. The dispersible tablet of claim 1 , wherein the purity of the compound of formula (3Z,5S)-5-(hydroxymethyl)-1-[(2′-methyl-1,1′-biphenyl-4-yl)carbonyl]pyrrolidin-3-one-O-methyloxime is from about 85% to about 99.9%.
5. The dispersible tablet of claim 1 , wherein the purity of the compound of formula (3Z,5S)-5-(hydroxymethyl)-1-[(2′-methyl-1,1′-biphenyl-4-yl)carbonyl]pyrrolidin-3-one-O-methyloxime is from about 90% to about 99.9%.
6. The dispersible tablet of claim 1 , wherein the purity of the compound of formula (3Z,5S)-5-(hydroxymethyl)-1-[(2′-methyl-1,1′-biphenyl-4-yl)carbonyl]pyrrolidin-3-one-O-methyloxime is from about 95% to about 99.9%.