Topical compositions for prostaglandin E1 delivery

Abstract

A topical composition of a semi-solid consistency suitable is provided for transdermal application of prostaglandin E1. The composition comprises prostaglandin E1, a penetration enhancer, a polysaccharide gum, a lipophilic compound, and an acidic buffer system. The penetration enhancer is an alkyl-2-(N,N-disubstituted amino)-alkanoate ester, an (N,N-disubstituted amino)-alkanol alkanoate, or a mixture of these. The lipophilic compound may be an aliphatic C1 to C8 alcohol, an aliphatic C8 to C30 ester, or a mixture of these. The composition includes a buffer system capable of providing a buffered pH value for said composition in the range of about 3 to about 7.4.

Description

[0001] technical field of invention

[0002] The invention relates to a pharmaceutical composition for transdermally administering prostaglandin drugs to patients. background of the invention

[0003] Prostaglandin E 1 It is prostanoic acid, a derivative of lipoic acid with 20 carbon atoms, represented by the following formula:

[0004] It is commercially available, for example, under the tradename "Alprostadil USP" from Chinoin Pharmaceutical and Chemical Processing Ltd. (Budapest, Hungary) and under the tradename "Prostin VR" from Upjohn Corporation (Kalamazoo, Michigan).

[0005] Prostaglandin E 1 Is a vasodilator used to maintain dilated blood vessels and is therefore especially used in the treatment of peripheral vascular disease. Although the potential advantages of transdermal delivery of prostaglandin El have long been recognized, major efforts to develop epidermal compositions for the delivery of prostaglandins have not been entirely successful to date.

[0006] ...

Examples

Embodiment 1

[0051] Example 1: Epidermal administration of prostaglandin E 1 Composition A

[0052] Composition A is prepared according to the following method, with 0.4 parts of prostaglandin E 1 (Alprostadil USP) was dissolved in 5 parts of ethanol to form part A, then 5 parts of dodecyl 2-(N,N-dimethylamino)propionate were mixed into the alcohol-prostaglandin E1 solution, followed by Parts of ethyl laurate.

[0053] Prepare Part B starting from a water / buffer solution at pH 5.5: by adding sufficient potassium phosphate monohydrate to pure water to obtain a 0.1M solution, with a strong base solution (1N sodium hydroxide) and a strong acid solution (1N phosphoric acid) Adjust the pH of the water / buffer solution to 5.5. The buffer solution comprises about 80 parts of the total composition.

[0054] Add 0.5 parts of ethyl laurate to the buffer solution, then disperse locust bean gum (powder) into the buffer solution, and homogenize with a homogenizer. Table 1 below lists the components....

Embodiment 2

[0060] Example 2: Epidermal administration of prostaglandin E 1 Composition B

[0061] Composition B was prepared using the ingredients listed in Table 1. Composition B contains more prostaglandin E than composition A 1 , Composition B exhibited similar semi-solid homogeneity and homogeneous appearance despite increased drug dosage. Determination of prostaglandin E according to the method described in implementation 1. 1 permeability. Composition B provides prostaglandin E 1 The relatively rapid and constant delivery, the results are listed in Table 2 and figure 1 middle.

Embodiment 3

[0062] Example 3: Epidermal administration of prostaglandin E 1 Composition C

[0063] Composition C was prepared using the ingredients listed in Table 1 below. Composition C contains more prostaglandin E than compositions A or B 1 , increasing the amount of drug had little (or no) effect on uniformity and appearance, and was actually comparable to composition A or B. Still measure prostaglandin E according to the method described in embodiment 1 1 permeability. According to this test, composition C also provides prostaglandin E 1 The relatively rapid and constant delivery of , the results are listed in Table 2 below and figure 1 middle.

[0001] technical field of invention

[0002] The invention relates to a pharmaceutical composition for transdermally administering prostaglandin drugs to patients. background of the invention

[0003] Prostaglandin E 1 It is prostanoic acid, a derivative of lipoic acid with 20 carbon atoms, represented by the following formula:

[0004] It is commercially available, for example, under the tradename "Alprostadil USP" from Chinoin Pharmaceutical and Chemical Processing Ltd. (Budapest, Hungary) and under the tradename "Prostin VR" from Upjohn Corporation (Kalamazoo, Michigan).

[0005] Prostaglandin E 1 Is a vasodilator used to maintain dilated blood vessels and is therefore especially used in the treatment of peripheral vascular disease. Although the potential advantages of transdermal delivery of prostaglandin El have long been recognized, major efforts to develop epidermal compositions for the delivery of prostaglandins have not been entirely successful to date.

[0006] ...

Examples

Embodiment 1

[0051] Example 1: Epidermal administration of prostaglandin E 1 Composition A

[0052] Composition A is prepared according to the following method, with 0.4 parts of prostaglandin E 1 (Alprostadil USP) was dissolved in 5 parts of ethanol to form part A, then 5 parts of dodecyl 2-(N,N-dimethylamino)propionate were mixed into the alcohol-prostaglandin E1 solution, followed by Parts of ethyl laurate.

[0053] Prepare Part B starting from a water / buffer solution at pH 5.5: by adding sufficient potassium phosphate monohydrate to pure water to obtain a 0.1M solution, with a strong base solution (1N sodium hydroxide) and a strong acid solution (1N phosphoric acid) Adjust the pH of the water / buffer solution to 5.5. The buffer solution comprises about 80 parts of the total composition.

[0054] Add 0.5 parts of ethyl laurate to the buffer solution, then disperse locust bean gum (powder) into the buffer solution, and homogenize with a homogenizer. Table 1 below lists the components....

Embodiment 2

[0060] Example 2: Epidermal administration of prostaglandin E 1 Composition B

[0061] Composition B was prepared using the ingredients listed in Table 1. Composition B contains more prostaglandin E than composition A 1 , Composition B exhibited similar semi-solid homogeneity and homogeneous appearance despite increased drug dosage. Determination of prostaglandin E according to the method described in implementation 1. 1 permeability. Composition B provides prostaglandin E 1 The relatively rapid and constant delivery, the results are listed in Table 2 and figure 1 middle.

Embodiment 3

[0062] Example 3: Epidermal administration of prostaglandin E 1 Composition C

[0063] Composition C was prepared using the ingredients listed in Table 1 below. Composition C contains more prostaglandin E than compositions A or B 1 , increasing the amount of drug had little (or no) effect on uniformity and appearance, and was actually comparable to composition A or B. Still measure prostaglandin E according to the method described in embodiment 1 1 permeability. According to this test, composition C also provides prostaglandin E 1 The relatively rapid and constant delivery of , the results are listed in Table 2 below and figure 1 middle.

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