CA1072447A - Stable solutions of chlortetracycline in aqueous 2-pyrrolidone - Google Patents
Stable solutions of chlortetracycline in aqueous 2-pyrrolidoneInfo
- Publication number
- CA1072447A CA1072447A CA268,277A CA268277A CA1072447A CA 1072447 A CA1072447 A CA 1072447A CA 268277 A CA268277 A CA 268277A CA 1072447 A CA1072447 A CA 1072447A
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- Prior art keywords
- pyrrolidone
- chlortetracycline
- weight
- solution
- solutions
- Prior art date
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- Pyrrole Compounds (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
Chlortetracycline aqueous solutions containing 2-pyr-rolidone as a co-solvent suitable for pharmaceutical use and especially useful for either oral, topical or parenteral adminis-tration are disclosed.
Chlortetracycline aqueous solutions containing 2-pyr-rolidone as a co-solvent suitable for pharmaceutical use and especially useful for either oral, topical or parenteral adminis-tration are disclosed.
Description
~ 7 This invention relates to antibiotie compositions suitable ¦
for pharmaceutical use. More particularl~ it relates to chlortetracycline solutions containing 2-pyrrolidone. ~ ¦
Previous efforts made to prepare high concentration chlor- ' 5 i tetracycline solutions have been unsuccessful. This is of ¦
I particular importance in the case of veter;nary parenteral ; compositions for administration to large animals.
Japanese Patent Publication No. Sho 47-303 discloses stable aqueous solutions of p-biphenylmethyl ~dl-tropyl-a-tropinium) bromide, 2.5%l in which 2 pyrrolidone is present in a concentration o 20%. The use of polyvinylpyrrolidone at a concentration of 30~/O is also disclosed. The pH o~ these ¦
solutions is less than 7, the preferred range being 3~4.
' Japanese Patent Publication No. Sho 43-1758 discloses insecticidal solutions containing hexachlorcyclohexane in alcohol and 2-pyrrolidone as solvents. T~le use o N-methyl pyrrolidone as a co-solvent is also disclosed.
British Patent Specification No. 802,111 discloses pesticidal compositions containing 2-pyrrolidone or N~methyl , pyrrolidone as solvents ~or DDT, dieldrin9 aldrin and similar ' I
-~ insecticides. The use of 67-82% of 2-pyrrolidone is exemplified,l .
7'~
British Patent Specification No. 805~026 discloses the !use of N-methyl pyrrolidone in concentrations of ~0% as a ¦solvent for various medicaments intended for parenteral ¦! administration, such as chloramphenicol, ~3~ dibenzyl l~ ethylenediamine-dipenicillin G and procaine penicillin.
U.S. Patent No. 2,987,437 discloses nematocidal compositions of 3,4-dichlorotetrahydrothia~hene, l,l-dioxide in 2-pyrrolidone.
German Patent No. 1,091,287 discloses stable aqueous solutions of tyro~hricin 0.25~L or subtili~ 0.2% for nasal or otic use prepared with the aid of pyrrolidione and/or , polyvinylpyrrolidone as solubilizers. Pyrrolidone is used in a concentration of 0.5% and polyvLnylpyrro~idone can be used up to 10%.
I U.S. Patent No. 3,062,717 discloses a~ueous parenteral ¦ solutions of tetracycline calcium complexes containing 35-80%
o an amide o~ acetic or lactic acid, such as N,M-dimethyl-acetamide or N-(~-hydroxyethyl) lactàmide, at a pH of 7 to 9.5.
Concentrations o~ 10 to 100 mg/ml are disclosed.
J. Pharm. Sci. 46, p. 458 (1957) discloses that oxytetracycline forms soluble complexes with N-methyl ¦ pyrrolidone in aqueous solution. The degree o~ interaction is limited by pH and solubility considerations.
U.S. Patent Application Serial No. 64~,295 discloses oxytetracycline solutions conta;ning from about 1 to 40 percent oxytetracycline in an aqueous vehicle containing from about 10 to 50 percent by weight of 2-pyrrolidone, about i 0.8 to 1.3 molar proportions of a pharmaceutically acceptable ¦ magnesium compound soluble in the said solution, said solution 3o having a pH value in the range of from ab~ut 7.5 to 9.5.
.. . .
for pharmaceutical use. More particularl~ it relates to chlortetracycline solutions containing 2-pyrrolidone. ~ ¦
Previous efforts made to prepare high concentration chlor- ' 5 i tetracycline solutions have been unsuccessful. This is of ¦
I particular importance in the case of veter;nary parenteral ; compositions for administration to large animals.
Japanese Patent Publication No. Sho 47-303 discloses stable aqueous solutions of p-biphenylmethyl ~dl-tropyl-a-tropinium) bromide, 2.5%l in which 2 pyrrolidone is present in a concentration o 20%. The use of polyvinylpyrrolidone at a concentration of 30~/O is also disclosed. The pH o~ these ¦
solutions is less than 7, the preferred range being 3~4.
' Japanese Patent Publication No. Sho 43-1758 discloses insecticidal solutions containing hexachlorcyclohexane in alcohol and 2-pyrrolidone as solvents. T~le use o N-methyl pyrrolidone as a co-solvent is also disclosed.
British Patent Specification No. 802,111 discloses pesticidal compositions containing 2-pyrrolidone or N~methyl , pyrrolidone as solvents ~or DDT, dieldrin9 aldrin and similar ' I
-~ insecticides. The use of 67-82% of 2-pyrrolidone is exemplified,l .
7'~
British Patent Specification No. 805~026 discloses the !use of N-methyl pyrrolidone in concentrations of ~0% as a ¦solvent for various medicaments intended for parenteral ¦! administration, such as chloramphenicol, ~3~ dibenzyl l~ ethylenediamine-dipenicillin G and procaine penicillin.
U.S. Patent No. 2,987,437 discloses nematocidal compositions of 3,4-dichlorotetrahydrothia~hene, l,l-dioxide in 2-pyrrolidone.
German Patent No. 1,091,287 discloses stable aqueous solutions of tyro~hricin 0.25~L or subtili~ 0.2% for nasal or otic use prepared with the aid of pyrrolidione and/or , polyvinylpyrrolidone as solubilizers. Pyrrolidone is used in a concentration of 0.5% and polyvLnylpyrro~idone can be used up to 10%.
I U.S. Patent No. 3,062,717 discloses a~ueous parenteral ¦ solutions of tetracycline calcium complexes containing 35-80%
o an amide o~ acetic or lactic acid, such as N,M-dimethyl-acetamide or N-(~-hydroxyethyl) lactàmide, at a pH of 7 to 9.5.
Concentrations o~ 10 to 100 mg/ml are disclosed.
J. Pharm. Sci. 46, p. 458 (1957) discloses that oxytetracycline forms soluble complexes with N-methyl ¦ pyrrolidone in aqueous solution. The degree o~ interaction is limited by pH and solubility considerations.
U.S. Patent Application Serial No. 64~,295 discloses oxytetracycline solutions conta;ning from about 1 to 40 percent oxytetracycline in an aqueous vehicle containing from about 10 to 50 percent by weight of 2-pyrrolidone, about i 0.8 to 1.3 molar proportions of a pharmaceutically acceptable ¦ magnesium compound soluble in the said solution, said solution 3o having a pH value in the range of from ab~ut 7.5 to 9.5.
.. . .
2- ~
7 Z ~ ~7 '' I f It h~s now been found that stable high potency solutions of chlortetracycline can be provided by means of a novel pharma-ceutical composition comprising an aqueous solution of fromI 1 about 5 to 20% by weight of an antibiotic compound selected S ¦from chlortetracycline and the pharmaceuticaily acceptable acid 1 addition salts thereof, about 2 to 4 molar proportions ¦based on said antibiotic of a pharmaceutically acceptablecalcium compound soluble in said solution, and from about 50 to 70% by weight of 2-pyrrolidone, said composition having .
a pH value in the range of from about 8 to 10 ,' l Chlortetracycline, the therapeutically-active componen~ of this invention, is a widely used tetracycline-type antibiotic.
It is particularly described in U.S. Patent No. 2,482,055.
An effective concentration range for chlortetr~cycline in the solutions of ~his invention is generally from about 5 to 20%
by weight of the total in the form of the free base or a pharmaceutically acceptable acid addition salt. The preferred form is the acid addition salt with the pre~erred concentra~ion bein~ from about 10 to 20% by weight, with the especially preferred concentration being from about 10 to 15% by weigh~.
Examp~es of suitable chlortetracycline acid addition salts 1l~hich can be used include such pharmaceutically acceptable I; acid addition salts as hydrochloride, hydrobromide and sulf2te.
IHowever, the preferred acid addition sale ~s chlortetracycline 25 I hydrochloride.
~f
7 Z ~ ~7 '' I f It h~s now been found that stable high potency solutions of chlortetracycline can be provided by means of a novel pharma-ceutical composition comprising an aqueous solution of fromI 1 about 5 to 20% by weight of an antibiotic compound selected S ¦from chlortetracycline and the pharmaceuticaily acceptable acid 1 addition salts thereof, about 2 to 4 molar proportions ¦based on said antibiotic of a pharmaceutically acceptablecalcium compound soluble in said solution, and from about 50 to 70% by weight of 2-pyrrolidone, said composition having .
a pH value in the range of from about 8 to 10 ,' l Chlortetracycline, the therapeutically-active componen~ of this invention, is a widely used tetracycline-type antibiotic.
It is particularly described in U.S. Patent No. 2,482,055.
An effective concentration range for chlortetr~cycline in the solutions of ~his invention is generally from about 5 to 20%
by weight of the total in the form of the free base or a pharmaceutically acceptable acid addition salt. The preferred form is the acid addition salt with the pre~erred concentra~ion bein~ from about 10 to 20% by weight, with the especially preferred concentration being from about 10 to 15% by weigh~.
Examp~es of suitable chlortetracycline acid addition salts 1l~hich can be used include such pharmaceutically acceptable I; acid addition salts as hydrochloride, hydrobromide and sulf2te.
IHowever, the preferred acid addition sale ~s chlortetracycline 25 I hydrochloride.
~f
-3--~; l D7Z4~7 ;
Calcium ions combine with chlortetracycline in solution to form calcium-tetracycline chela~es. Calcium chloride is a convenient and preferred source of calcium ions, but other compounds useful for the purpose of this invention , include calcium oxide, calcium acetate and calcium sulfate.
The molar ratio of calcium to chlortetracycline in these compositions is about from 2 to 4. This ratio is advisable to produce clear stable solut}ons.
'll 2-Pyrrolidone is present as a co-solvent in a concentration I
of from about 50 to 70%, and preferably from abou~ ~0 to 70%
based on the total weight of the composition. 2-Pyrrolidone t is also known as 2-pyrrolidinone, 2-oxopyrxolidine, , a-pyrrolidone and 2-ketopyrrolidine. It has an oral LD50 of , 8 gm/kg in rats and 3.8 gm/kg by intrape~itoneal injection in 15 ~; mice. Its use allows for minimum volume per dose and excellent ', satisfactory due to low viscosity of t'ne resultant composition.
, As an optional ingredient polyvinylpyrrolidone ! may also be present in a concentration of from about 1 to 7%
,, by weight. The polyvinylpyrrolidone preferred for this 20 'I inyention is one having an average molecular weight o bet~een about 5,000 and 100,000 (K-12 to 30) and especially between , about 10,000 and 17,000 ~K - 17). It is present in ` part as a cosolubilizer and may improve tissue toleration.
,~ The stability of these solutions for therapeutic 25 , administration is still further enchanced by the use of antioxidants such as sodium or magnesium formaldehyde sulfoxylate and monothioglycerol at levels of from about 0.01 to 100%
by weight. -.~ . I
107Z~7 ¦I The pH value is adjusted if necessary to pH 8 to 10. The ¦ preferred range is pH 8.5 to 9. 5. The pH can be adjusted with an ! organic base such as monoethanolamine or with a pharmaceutically ¦l acceptable acicl, such as hydrochloric acid.
5 ¦~ The compositions of this invention are readily prepared by mixing the calcium compound with the 2-pyrrolidone and water at about 50C and slowly adding the chlortetracycline antibiotic !
with stirring and adjusting the pH to the desired range. If polyvinylpyrrolidone is to be included it is added to the 2-pyrrolidone and wa~er before the addition of the ¦ calcium compound as previously described.
These compositions are also easy to syringe over a wide temperature range and are satisfactory from a physical and ¦ chemical stability standpoint.
¦ The use of these high potoncy chlortetracycline compositions ¦¦ enables a reduction of the numb~or of injections that must be administered to large animals, such.as steers, in order to receive an effective dose.
The primary application is as a parenteral composition ¦, but the new compositions can also be used for topical or oral ~ ap~lication.
I
., .
. .
~07;;~4~ 7 EX~PLE 1 ¦il The following solution con~aining 100 mg/ml of chlortetra-¦, cycline hydrochloride activity was prepared.
Il gm~100 ml 5 i¦ Chlortetracycline hydrochloride (based on a chlortetracycline hydrochloride potency llf 950~/mg plus a 5~ overage) 11.053 ¦I Calcium chloride ~.96 ji 2-Pyrrolidone 60.00 10 ,I Monothioglycerol 1.00 Il Monoethanolamine, to adjust pH to 8.8 ¦IWater q.s. to 100 ml I¦ The 2-pyrrolidone was mixed with water. The solution was ¦!heated to about 50C. and the monothioglycerol was added and i dissolved with stirring. The calcium chloride was then slurried ¦~with the solution. The chlortetracycline hydrochloride was !islowly added with stirring and the pH raised with monoethanol-¦¦ amine until solution resulted. The solution was allowed to cool lito room temperature and the pH adjusted to 8.8 with monoethanol- i 20 1¦ amine. The solution was then brought up to volume with water.
Solutions comparable to the above were also made by adjustin~
the pH to 8.0 and 9.5 respec~ively.
,, 1,1, ' . I
I
. I
. .
~7Z~
EXA~iPLE 2 The following solution containing 100 mg/ml of chlortekra~
¦ cycline hydrochloride activity was prepared using the procedure , described in Example 1.
5 I gm/100 ml Chlortetracycline hydrochloride (based on a chlortetracycline hydrochloride potency of 950~/mg plus a 5~ overage) 11.053 Calcium chloride 9.92 1 2-Pyrrolidone 60.00 Monothioglycerol 1.00 Monoethanolamine, to adjust pH to 8.8 I Water q.s. to 100 ml ¦i Solutions comparable to the above were also made by adjusting the pH to 8.0 and 9.5 respectivelyf _XAMPLE 3 The following solution containing 50 mg~ml of chlortetra-l cycline hydrochloride activity was prepared.
¦ gm/100 ml 1 Chlortetracycline h~drochloride (based on a chlortetracycline h~drochloride potency ¦ of 950 ~/mg plus a 5~ overage) 5.527 Calcium chloride 2.48 1 2-Pyrrolidone 50.00 25 i Polyvinylpyrrolidone 5.00 I~ Monothioglycerol 1.00 ! Monoethanolamine, to adjust pH to 8.8 ¦I Water q.s. to 100 ml l~ The 2=pyrrolidone was mixed with water~ Polyvinylpyrrolidone I" was then added with stirring until dissolved. The procedure described in Example 1 was then followed.
Solutions comparable to the above were also made by adjusting the pH to 8.0 and 9.5 respectively.
.. . . , - - , . . .. .
z~
The follow.ing solution containing 200 mg/ml of chlortetra-I cycline hydrochloride activity was prepared using the procedure ¦described in Example 1.
m/100 ml ~ Chlo~tetracycline hydrochloride (based on ¦ a chlortetracycline hydrochloride potency f 950 ~/mg plus a 5% overage~ ~2,1Q6 ¦ Calcium chloride 9.92 !2-Pyrrolidone 60.00 ¦ Monothioglycerol . ~.00 iMonoethanolamine, to adjust pH to 8.8 ~jWater q.s. to 100 ml I Solutions comparable to the above were also made by adjusting 1l the pH to 8.0 and 9.5 respectively.
i EX~lPLE 5 The following solution containing 100 mg/ml of chlortetra-cycline hydrochloride activity was prepared using the procedure Ijdescribed in Example 1.
2~ m/100 ml ¦,Chlortetracycline hydrochloride (based on a chlortetracycline hydrochloride potency 11f 950 ~/mg plus a 5% overage) 11.053 IiCalcium chloride 4.9~
2~ ~12-Pyrrolidone 70,00 .IMonothioglycerol 1~00 Monoethanolamine, to adjust pH to 8.8 Water q.s. to 100 ml I, Solutions comparable to the above were also made by adjusting 3 I the pH to 8.0 and 9.5 respectively.
... .. ..... ... . ... . . ... . .. . . . . . . .
I . ~L0~24~
l EXAMPLE 6 l l _ . .
The following solu~ion containing lOO m~/ml of chlortetra-cycline hydrochloride activity was prepare~ using the procedure Idescribed in Example 3. ` .
5 ! gm/lOO ml Chlortetracycline hydrochloride (based on . .
a chlortetracycline hydrochloride potency of 950 ~/mg plus a ~% overage) 11.053 !Calcium chloride 4.96 2-Pyrrolidone . 60.00 ¦Polyvinylpyrrolidone 5.00 ¦Monothioglycerol 1,00 ¦ ~onoethanolamine, to adjust pH to 8.8 ~jWater q.s. to lOO ml ~I Solutions comparable to the above were also made by adjusting ~ llthe pE to 8 0 and 9.5 respectively.
_g_ ~
Calcium ions combine with chlortetracycline in solution to form calcium-tetracycline chela~es. Calcium chloride is a convenient and preferred source of calcium ions, but other compounds useful for the purpose of this invention , include calcium oxide, calcium acetate and calcium sulfate.
The molar ratio of calcium to chlortetracycline in these compositions is about from 2 to 4. This ratio is advisable to produce clear stable solut}ons.
'll 2-Pyrrolidone is present as a co-solvent in a concentration I
of from about 50 to 70%, and preferably from abou~ ~0 to 70%
based on the total weight of the composition. 2-Pyrrolidone t is also known as 2-pyrrolidinone, 2-oxopyrxolidine, , a-pyrrolidone and 2-ketopyrrolidine. It has an oral LD50 of , 8 gm/kg in rats and 3.8 gm/kg by intrape~itoneal injection in 15 ~; mice. Its use allows for minimum volume per dose and excellent ', satisfactory due to low viscosity of t'ne resultant composition.
, As an optional ingredient polyvinylpyrrolidone ! may also be present in a concentration of from about 1 to 7%
,, by weight. The polyvinylpyrrolidone preferred for this 20 'I inyention is one having an average molecular weight o bet~een about 5,000 and 100,000 (K-12 to 30) and especially between , about 10,000 and 17,000 ~K - 17). It is present in ` part as a cosolubilizer and may improve tissue toleration.
,~ The stability of these solutions for therapeutic 25 , administration is still further enchanced by the use of antioxidants such as sodium or magnesium formaldehyde sulfoxylate and monothioglycerol at levels of from about 0.01 to 100%
by weight. -.~ . I
107Z~7 ¦I The pH value is adjusted if necessary to pH 8 to 10. The ¦ preferred range is pH 8.5 to 9. 5. The pH can be adjusted with an ! organic base such as monoethanolamine or with a pharmaceutically ¦l acceptable acicl, such as hydrochloric acid.
5 ¦~ The compositions of this invention are readily prepared by mixing the calcium compound with the 2-pyrrolidone and water at about 50C and slowly adding the chlortetracycline antibiotic !
with stirring and adjusting the pH to the desired range. If polyvinylpyrrolidone is to be included it is added to the 2-pyrrolidone and wa~er before the addition of the ¦ calcium compound as previously described.
These compositions are also easy to syringe over a wide temperature range and are satisfactory from a physical and ¦ chemical stability standpoint.
¦ The use of these high potoncy chlortetracycline compositions ¦¦ enables a reduction of the numb~or of injections that must be administered to large animals, such.as steers, in order to receive an effective dose.
The primary application is as a parenteral composition ¦, but the new compositions can also be used for topical or oral ~ ap~lication.
I
., .
. .
~07;;~4~ 7 EX~PLE 1 ¦il The following solution con~aining 100 mg/ml of chlortetra-¦, cycline hydrochloride activity was prepared.
Il gm~100 ml 5 i¦ Chlortetracycline hydrochloride (based on a chlortetracycline hydrochloride potency llf 950~/mg plus a 5~ overage) 11.053 ¦I Calcium chloride ~.96 ji 2-Pyrrolidone 60.00 10 ,I Monothioglycerol 1.00 Il Monoethanolamine, to adjust pH to 8.8 ¦IWater q.s. to 100 ml I¦ The 2-pyrrolidone was mixed with water. The solution was ¦!heated to about 50C. and the monothioglycerol was added and i dissolved with stirring. The calcium chloride was then slurried ¦~with the solution. The chlortetracycline hydrochloride was !islowly added with stirring and the pH raised with monoethanol-¦¦ amine until solution resulted. The solution was allowed to cool lito room temperature and the pH adjusted to 8.8 with monoethanol- i 20 1¦ amine. The solution was then brought up to volume with water.
Solutions comparable to the above were also made by adjustin~
the pH to 8.0 and 9.5 respec~ively.
,, 1,1, ' . I
I
. I
. .
~7Z~
EXA~iPLE 2 The following solution containing 100 mg/ml of chlortekra~
¦ cycline hydrochloride activity was prepared using the procedure , described in Example 1.
5 I gm/100 ml Chlortetracycline hydrochloride (based on a chlortetracycline hydrochloride potency of 950~/mg plus a 5~ overage) 11.053 Calcium chloride 9.92 1 2-Pyrrolidone 60.00 Monothioglycerol 1.00 Monoethanolamine, to adjust pH to 8.8 I Water q.s. to 100 ml ¦i Solutions comparable to the above were also made by adjusting the pH to 8.0 and 9.5 respectivelyf _XAMPLE 3 The following solution containing 50 mg~ml of chlortetra-l cycline hydrochloride activity was prepared.
¦ gm/100 ml 1 Chlortetracycline h~drochloride (based on a chlortetracycline h~drochloride potency ¦ of 950 ~/mg plus a 5~ overage) 5.527 Calcium chloride 2.48 1 2-Pyrrolidone 50.00 25 i Polyvinylpyrrolidone 5.00 I~ Monothioglycerol 1.00 ! Monoethanolamine, to adjust pH to 8.8 ¦I Water q.s. to 100 ml l~ The 2=pyrrolidone was mixed with water~ Polyvinylpyrrolidone I" was then added with stirring until dissolved. The procedure described in Example 1 was then followed.
Solutions comparable to the above were also made by adjusting the pH to 8.0 and 9.5 respectively.
.. . . , - - , . . .. .
z~
The follow.ing solution containing 200 mg/ml of chlortetra-I cycline hydrochloride activity was prepared using the procedure ¦described in Example 1.
m/100 ml ~ Chlo~tetracycline hydrochloride (based on ¦ a chlortetracycline hydrochloride potency f 950 ~/mg plus a 5% overage~ ~2,1Q6 ¦ Calcium chloride 9.92 !2-Pyrrolidone 60.00 ¦ Monothioglycerol . ~.00 iMonoethanolamine, to adjust pH to 8.8 ~jWater q.s. to 100 ml I Solutions comparable to the above were also made by adjusting 1l the pH to 8.0 and 9.5 respectively.
i EX~lPLE 5 The following solution containing 100 mg/ml of chlortetra-cycline hydrochloride activity was prepared using the procedure Ijdescribed in Example 1.
2~ m/100 ml ¦,Chlortetracycline hydrochloride (based on a chlortetracycline hydrochloride potency 11f 950 ~/mg plus a 5% overage) 11.053 IiCalcium chloride 4.9~
2~ ~12-Pyrrolidone 70,00 .IMonothioglycerol 1~00 Monoethanolamine, to adjust pH to 8.8 Water q.s. to 100 ml I, Solutions comparable to the above were also made by adjusting 3 I the pH to 8.0 and 9.5 respectively.
... .. ..... ... . ... . . ... . .. . . . . . . .
I . ~L0~24~
l EXAMPLE 6 l l _ . .
The following solu~ion containing lOO m~/ml of chlortetra-cycline hydrochloride activity was prepare~ using the procedure Idescribed in Example 3. ` .
5 ! gm/lOO ml Chlortetracycline hydrochloride (based on . .
a chlortetracycline hydrochloride potency of 950 ~/mg plus a ~% overage) 11.053 !Calcium chloride 4.96 2-Pyrrolidone . 60.00 ¦Polyvinylpyrrolidone 5.00 ¦Monothioglycerol 1,00 ¦ ~onoethanolamine, to adjust pH to 8.8 ~jWater q.s. to lOO ml ~I Solutions comparable to the above were also made by adjusting ~ llthe pE to 8 0 and 9.5 respectively.
_g_ ~
Claims (3)
1. A stable chloretetracycline antibiotic liquid composition which comprises a solution of from about 5 to 20%
by weight of chlortetracycline or a pharmaceutically-acceptable acid addition salt thereof and from about 2 to 4 molar proportions based on said chlortetracycline of a pharmaceutically-acceptable calcium compound dissolved in aqueous 2-pyrrolidone, and the pH
of the solution being from about 8 to 10, and the 2-pyrrolidone being present at a concentration of about 50 to 70% by weight of the said composition.
by weight of chlortetracycline or a pharmaceutically-acceptable acid addition salt thereof and from about 2 to 4 molar proportions based on said chlortetracycline of a pharmaceutically-acceptable calcium compound dissolved in aqueous 2-pyrrolidone, and the pH
of the solution being from about 8 to 10, and the 2-pyrrolidone being present at a concentration of about 50 to 70% by weight of the said composition.
2. A composition according to claim 1, wherein the said calcium compound is calcium chloride.
3. A composition according to claim 1, wherein polyvinylpyrrolidone having an average molecular weight of from 5,000 to 100,000 is also present in a concentration of from about 1 to 7% by weight of the total composition.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA268,277A CA1072447A (en) | 1976-12-20 | 1976-12-20 | Stable solutions of chlortetracycline in aqueous 2-pyrrolidone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA268,277A CA1072447A (en) | 1976-12-20 | 1976-12-20 | Stable solutions of chlortetracycline in aqueous 2-pyrrolidone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1072447A true CA1072447A (en) | 1980-02-26 |
Family
ID=4107544
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA268,277A Expired CA1072447A (en) | 1976-12-20 | 1976-12-20 | Stable solutions of chlortetracycline in aqueous 2-pyrrolidone |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1072447A (en) |
-
1976
- 1976-12-20 CA CA268,277A patent/CA1072447A/en not_active Expired
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