WO2019132823A1

WO2019132823A1 - A pharmaceutical product comprising levodropropizine

Info

Publication number: WO2019132823A1
Application number: PCT/TR2018/050654
Authority: WO
Inventors: Umit Cifter; Urun Kandemirer; Aylin SENTURK
Original assignee: Biofarma Ilac Sanayi Ve Ticaret A.S.
Priority date: 2017-12-27
Filing date: 2018-11-05
Publication date: 2019-07-04
Also published as: TR201722102A2

Abstract

The invention is related to an oral pharmaceutical product in chewable tablet form comprising levodropropizine active agent for use in the symptomatic treatment of cough.

Description

DESCRIPTION

A PHARMACEUTICAL PRODUCT COMPRISING LEVODROPROPIZINE

Technical Field

The present invention, to be used in the symptomatic treatment of cough, is related to a pharmaceutical product comprising levodropropizine as an active ingredient.

Prior Art

Cough is a reflex that protects the lungs against aspiration and provides throwing of the over-secretion produced via body. Cough which is a defense mechanism of the respiratory system is one of the most common symptoms. Cough is accompanied by reflex-developing bronchoconstriction and this event increases the sensitivity of cough-inducing receptors in the lungs. Levodropropizine active agent is a highly effective antitussive drug for relieving cough. Like all peripherally - acting antitussive drugs, levodropropizine also inhibits cough reflex by its spasmolytic and / or anesthetic effects. The spasmolytic effect of levodropropizine reduces indirectly the sensitivity of cough-related sensory receptors found in the lungs.

In the state of the art levodropropizine which is a cough-relieving molecule with being a (-) - (S) -isomer of Dropropizine is named (-) - (S) -3- (4-Phenylpiperazine-l-yl) propane- 1,2- diol (IUPAC); characterized by the following formula 1 as chemically:

Formula 1

Levodropropizine is used by oral route. The bioavailability of the levodropropizine, which is rapidly absorbed by oral route, is over 75%. Besides, it binds to the plasma proteins at low rate and is rapidly dispersed after absorption. In the patent document of W02017091165 in the state of the art, a combination of liquid dosage pharmaceutical form of levodropropizine and sugar is mentioned. In the document, sugar is used to enhance the stability of the liquid formulation and as a sweetener. Furthermore, it has also been mentioned that the amount of impurity created by the N- Oxygen bond is reduced to a pharmaceutically acceptable amount with the sugar used. Even though it is also mentioned in the document that the amount of impurity created by the N-Oxygen bond is reduced by the sugar used, the stability problems that occur by virtue of liquid form will be more than tablet forms.

In another patent document of WO2016154503 in the state of the art, an oral pharmaceutical composition comprising a shell surrounding a matrix and suitable for chewing, soaking or sublingual use is mentioned. In the document, a large number of active ingredients including levodropropizine is given in the form of liquid soft capsules. In the state of the art, liquid soft capsules have difficulties in production and stability.

The liquid forms of levodropropizine given in the state of the art are generally presented in the market as syrup. Although syrups take an attractive situation because of the sweets and aromas they contain, it is pretty difficult to maintain their homogeneity due to the high concentration of sugars in their content. Despite the fact that high-concentration sugar prevents the reproduction of microorganisms in the syrup, it is required protective substances for precaution and this situation causes the syrup to be less preferred.

The syrups, which are generally stored in glass bottles are in contact with the air when the caps are opened. Contamination, which can occur as a result of this situation and the patient's miss-use, can lead to stability problems. For this reason, the usage time of syrups can be shortened. Beside of these, it is difficult for the user to provide a dose adjustment by the scale for the syrups. Pharmaceutical products in liquid form such as syrup can cause problems in case of transported in outside (spillage due to not closing the bottle cap tightly, spread, the need for repurchase due to the decrease in the amount, etc.), even though they are suitable for domestic consumption. This reduces patient comfort.

On the other hand, the production processes of liquid soft capsules which are in another state of the art are very difficult. In addition to taking too much time, many materials are wasted during production. While it already has an expensive production technique, a high costly pharmaceutical form arises by taking this situation into the account. This situation makes difficult to reach the drug for the patient and hence patient comfort in the treatment of a common symptom, such as cough.

It is necessary to improve a pharmaceutical form to ensure a high proportion of the patient comfort and to remove the said negativeness of the in the state of the art. There is no levodropropizine active agent product developed in the form of a chewable tablet in the state of the art.

Brief Description of the Invention

The aim of the invention is to develop an easy-to-use pharmaceutical product comprising the levodropropizine as an active ingredient, which has an antitussive effect against the common cough symptom.

The pharmaceutical product developed to achieve this purpose is in the form of a chewable tablet. It is aimed to improve patient comfort with the said pharmaceutical product being in the form of a chewable tablet. Patients who need to be treated with an antitussive effective drug; especially for patients who have swallowing difficulty, children and the elderly, the use of this active substance is facilitated by the fact that the pharmaceutical form is a chewable tablet. Thus, the use contunity of the drug is ensured.

Detailed Description of the Invention

The disclosed pharmaceutical product comprises levodopropizine as an active agent (active ingredient or active substance). Levodropropizine is an active agent which has antitussive property and is used in the symptomatic treatment of cough.

The disclosed pharmaceutical product is in a form that the user can use quite easily. The said product is used orally and but no limited to these, is in tablet form in the preferred embodiment of the invention. The preferred form in this said embodiment is the chewable tablet.

Chewable tablets are quickly dispersed into the small pieces in the mouth as a result of chewing due to their properties. In this way, the swallowing of active ingredients by dispersed causes rapid release and absorption of them in the gastrointestinal tract (stomach, intestines). Since chewable tablets are getting smaller when they dispersed in the mouth, the size of the tablet is not very important compared to other tablet forms. At the same time, it can also be prefered quite easily in order to achieve the desired therapeutic effect in situations requiring high-dose. In patients who suffering from swallowing difficulty, children and the elderly, it provides a more effective patient comfort minimizing the problem of swallowing difficulty. The disclosed pharmaceutical product in the form of a chewable tablet, makes it particularly preferable for children. This product is in the form of a chewable tablet, so no water is needed. Thus, it is easy to use the medication at any time and everywhere. This situation provides a great advantage especially for patients who have swallowing difficulty, patients with disabilities and patients who have a sudden coughing crisis. In chewable tablets, stability conditions are more easily achieved compared to liquid forms. Furthermore, it is quite easy to prevent conditions that will increase the impurities caused by oxidation in chewable tablets compared to liquid form. In terms of the process, the production cost of chewable tablets is especially low compared to liquid soft capsules and production techniques do not take much time. In addition, waste of material is low in chewable tablets during production compared to liquid soft capsules. Since the cost of production is low, it is easier to supply the medication to the patient. Unlike liquid soft capsules or chewable soft capsules, the products of this form do not harden over time. There are no unwanted situations such as degradation when it contacts with the air, loss of homogeneity over time which is seen in liquid forms. Due to the fact that it is in tablet form, it is also prevented from being taken in the wrong dose.

All of these aforementioned features for chewable tablets will raise the patient comfort to higher levels against the common cough symptom as an alternative to the disadvantages of the state of the art.

Various excipients are used in the disclosed invention of the chewable tablet preparation. The pharmaceutical product comprising excipients such as at least one disintegrant and/or at least one diluent and/or at least one flavour and/or at least one taste regulator and/or at least one flavorant and/or at least one glidant and/or at least one lubricant and/or at least one colourant, but not limited to described herein.

The invention is not limited to the embodiments disclosed above and a skilled person in the art can perform different embodiments of the invention easily. They should be evaluated within the scope of the invention protection demanded with claims.

Claims

1. The invention is a pharmaceutical product comprising levodropropizine administered orally characterized by the fact that the pharmaceutical form is a chewable tablet form.