Orodispersible film composition comprising enalapril for the treatment of hypertension in a pediatric population
Inventors
Karavas, Evangelos • KOUTRIS, EFTHYMIOS • SAMARA, VASILIKI • Koutri, Ioanna • Kalaskani, Anastasia • Kalantzi, Lida • KAKOURIS, ANDREAS • Diakidou, Amalia • GOTZAMANIS, GEORGE • GEORGOUSIS, ZAHARIAS • Konstanti, Louiza
Assignees
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Publication Number
US-11154585-B2
Publication Date
2021-10-26
Expiration Date
Abstract
The present invention relates to an oral applicable therapeutic dosage form, in particular an orodispersible film comprising Enalapril or pharmaceutically acceptable salts thereof for use in the treatment of hypertension in a pediatric population. The pediatric population is defined from 1 to 18 years of age. The present invention also provides a method of manufacturing of such a dosage form.
Core Innovation
The patent describes an orodispersible film dosage form for treating hypertension that comprises Enalapril or a pharmaceutically acceptable salt thereof, at least one water-soluble polymer, and an effective amount of a pH increasing agent. The water-soluble polymer is a combination of pullulan and modified starch, present at 55 to 75% w/w of the total weight of the film, with a pullulan to modified starch ratio from 1:1 to 1:2. The orodispersible film dosage form disintegrates within less than two minutes when placed onto a tongue.
The film further specifies that the pH increasing agent increases the film pH, with a film pH stated as 6.4 to 6.5. The pH increasing agent is described as NaOH in a concentration range of 1 to 3% w/w of the total weight of the film. The patent describes that increasing the casting-solution/film pH improves Enalapril stability by reducing impurities, and it addresses disintegration performance and stability under relative humidity conditions.
The polymer system is presented as pullulan plus modified starch, including modified starch such as Lycoat®, together with formulation excipients and film characteristics to support fast disintegration. Named excipients include glycerol as a plasticizer, polysorbate 80 as a surfactant, and sucralose as a sweetener. The described approach includes manufacturing by forming a homogenous casting solution, casting onto a specified coated paper, and drying at controlled conditions.
Claims Coverage
The independent claims cover an orodispersible film composition and a corresponding manufacturing process. The inventive features are centered on Enalapril plus a pullulan/modified starch polymer system combined with a pH increasing agent, and on nitrogen/vacuum-mixer casting and defined post-processing into sachets and color-differentiated packaging.
Orodissolvable Enalapril film with pullulan and modified starch plus pH increasing agent
An orodispersible film dosage form comprising Enalapril or a pharmaceutically acceptable salt thereof and at least one water-soluble polymer and an effective amount of a pH increasing agent, wherein the water soluble polymer is a combination of pullulan and modified starch in an amount of from 55 to 75% w/w of the total weight of the film, wherein the ratio between pullulan and modified starch is from 1:1 to 1:2, and wherein the orodispersible film dosage form disintegrates within less than two minutes when placed onto a tongue.
Nitrogen/vacuum-mixer process to manufacture the Enalapril pullulan/modified starch pH-increasing orodispersible film
A process of manufacturing an orodispersible film, dispensing and weighing raw materials; mixing Enalapril maleate, a combination of water-soluble polymers, a pH increasing agent, a surfactant, a plasticizing agent, a sweetener and water under a nitrogen blanketing in a vacuum mixer until a homogenous casting solution has been formed; casting the solution on a one-sided PE/silicon coated paper and drying the solution at 40°C for 4 hours; cutting and converting reels of film into single dose sachets; packaging sachets into a secondary laminated foil packaging with a different color according to dosage strength; wherein the orodispersible film comprises Enalapril or a pharmaceutically acceptable salt thereof and at least one water-soluble polymer and an effective amount of a pH increasing agent, wherein the water soluble polymer is a combination of pullulan and modified starch in an amount of from 55 to 75% w/w of the total weight of the film, and wherein the ratio between pullulan and modified starch is from 1:1 to 1:2.
Across the independent claims, the protection is directed to fast-disintegrating Enalapril orodispersible films using a pullulan/modified starch water-soluble polymer system with a pH increasing agent, and to a manufacturing route that forms a homogenous casting solution under nitrogen/vacuum mixing, casts onto a PE/silicon coated paper, dries at controlled conditions, converts into single-dose sachets, and packages with color differentiation by dosage strength.
Stated Advantages
Improves Enalapril stability by reducing impurities.
Improves film performance, including disintegration time and behavior under relative humidity conditions.
Documented Applications
Treating hypertension in a pediatric population by administering the orodispersible films.
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