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US 11,890,273 B2Granted
Losartan liquid formulations and methods of use
AssigneeScienture, Inc.
InventorsBhavya Teja Kolla, Rahul Surana, Suketu Sanghvi, Jigar Bhatt
Life of this patent
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Abstract
The present disclosure relates to stable, liquid pharmaceutical compositions of losartan or pharmaceutically acceptable salts thereof for oral administration. The present disclosure further provides powder compositions for reconstitution to provide a liquid formulation. In further aspects, the present disclosure relates to processes for preparation of such pharmaceutical compositions, and methods of treating a subject in need of losartan by administration of a formulation described herein.
Claims20
An oral pharmaceutical composition comprising:
- i.) about 1 mg/mL to about 10 mg/mL of losartan or a pharmaceutically acceptable salt thereof,
- ii.) about 0.5 mg/mL to about 1.5 mg/mL of a suspending agent selected from the group consisting of hydroxyethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, sodium carboxymethylcellulose, xanthan gum, acacia, an alginate, and guar gum, or a combination thereof,
- iii.) a pH modifying agent,
- iv.) about 5 mg/mL to about 15 mg/mL of a crystallization inhibitor selected from the group consisting of polyvinylpyrrolidone, hydroxypropyl methylcellulose, polyvinyl acetate, cyclodextrin, and hydroxypropyl P-cyclodextrin, or a combination thereof,
- v.) about 0.1 mg/mL to about 3 mg/mL of a preservative selected from the group consisting of methyl paraben, ethyl paraben, propyl paraben, butyl paraben, benzoic acid, sodium benzoate, and benzalkonium chloride, or a combination thereof,
- vi.) about 1 mg/mL to about 10 mg/mL of an antifoaming agent, and
- vii.) about 20 mg/mL to about 60 mg/mL of a solubilizer selected from the group consisting of cremophor, vitamin E, polyethylene glycol (PEG 400), propylene glycol, and co-solvent, or a combination thereof, and
- wherein the pharmaceutical composition is a suspension,
- wherein the suspension has a pH of about 7, and
- wherein the suspension has the following characteristics after storage at room temperature and 60% relative humidity:
- after 12 months of storage, the suspension comprises less than about 0.5 wt/wt % losartan impurity D and losartan impurity E, relative to the weight of losartan in the suspension, and
- after 12 months of storage, the suspension comprises at least about 95% of the losartan that was in the suspension prior to storage.
9 more elements
An oral pharmaceutical composition comprising:
- i.) about 1 mg/mL to about 10 mg/mL of losartan or a pharmaceutically acceptable salt thereof,
- ii.) about 0.5 mg/mL to about 1.5 mg/mL of a suspending agent selected from the group consisting of hydroxyethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, sodium carboxymethylcellulose, xanthan gum, acacia, an alginate, and guar gum, or a combination thereof,
- iii.) about 0.5 mg/mL to about 1.5 mg/mL of a pH modifying agent,
- iv.) about 5 mg/mL to about 15 mg/mL of a crystallization inhibitor selected from the group consisting of polyvinylpyrrolidone, hydroxypropyl methylcellulose, polyvinyl acetate, cyclodextrin, and hydroxypropyl P-cyclodextrin, or a combination thereof,
- v.) about 0.1 mg/mL to about 3 mg/mL of a preservative selected from the group consisting of methyl paraben, ethyl paraben, propyl paraben, butyl paraben, benzoic acid, sodium benzoate, and benzalkonium chloride, or a combination thereof,
- vi.) about 1 mg/mL to about 10 mg/mL of an antifoaming agent, and
- vii.) about 20 mg/mL to about 60 mg/mL of a solubilizer selected from the group consisting of cremophor, vitamin E, polyethylene glycol (PEG 400), propylene glycol, and co-solvent, or a combination thereof, and
- wherein the pharmaceutical composition is a suspension,
- wherein the suspension has a pH of about 7;
- and
- wherein the pharmaceutical composition is stable for 6 months at 40° C. at 75% relative humidity, and wherein stability is determined by the pharmaceutical composition having the following characteristics after storage at 40° C. at 75% relative humidity:
- after 6 months of storage, the suspension comprises less than about 2 wt/wt % losartan impurity D and losartan impurity E, relative to the weight of losartan in the suspension, and after 6 months of storage, the suspension comprises at least about 97% of the amount of losartan in the suspension prior to storage;
- or
- wherein the pharmaceutical composition is stable for 12 months at 30° C. at 65% relative humidity, wherein stability is determined by the pharmaceutical composition having one or both of the following characteristics after storage at 30° C. at 65% relative humidity:
- after 12 months of storage, the suspension comprises less than about 1 wt/wt % losartan impurity D and losartan impurity E, relative to the weight of losartan in the suspension, and
- after 12 months of storage, the suspension comprises at least about 98% of the amount of losartan in the suspension prior to storage;
- or
- wherein the pharmaceutical composition is stable for 12 months at 2-8° C., wherein stability is determined by the pharmaceutical compositions having one or both of the following characteristics after storage at 2-8° C.;
- after 12 months of storage, the suspension comprises less than about 0.5 wt/wt % losartan impurity D and losartan impurity E, relative to the weight of losartan in the suspension, and
- after 12 months of storage, the suspension comprises at least about 99% of the amount of losartan in the suspension prior to storage.
17 more elements
An oral pharmaceutical composition comprising:
- i.) about 1 mg/mL to about 10 mg/mL of losartan or a pharmaceutically acceptable salt thereof,
- ii.) about 0.5 mg/mL to about 1.5 mg/mL of a suspending agent selected from the group consisting of hydroxyethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, microcrystalline cellulose, sodium carboxymethylcellulose, xanthan gum, acacia, an alginate, and guar gum, or a combination thereof,
- iii.) a pH modifying agent, and
- iv.) about 0.1 mg/mL to about 3 mg/mL of a preservative,
- wherein the pharmaceutical composition is a suspension,
- wherein the suspension has a pH of about 7, and
- wherein the suspension has the following characteristics after storage at room temperature and 60% relative humidity:
- after 12 months of storage, the suspension comprises less than about 0.5 wt/wt % losartan impurity D and losartan impurity E, relative to the weight of losartan in the suspension, and
- after 12 months of storage, the suspension comprises at least about 95% of the losartan that was in the suspension prior to storage.
6 more elements
Dependencies are inferred from the claim text.