WO2022157809A1

WO2022157809A1 - Administration vehicle for oral pharmaceutical formulations and process of preparation thereof

Info

Publication number: WO2022157809A1
Application number: PCT/IN2022/050049
Authority: WO
Inventors: Atul Sajgure; Vasanti SAJGURE
Original assignee: Atul Sajgure; Sajgure Vasanti
Priority date: 2021-01-24
Filing date: 2022-01-21
Publication date: 2022-07-28

Abstract

The present disclosure provides an administration vehicle for oral pharmaceutical formulations that comprises at least one mucinous extract of the plant Abelmoschus esculentus in an amount ranging from 9 to 24 weight %; at least one flavoring agent in an amount ranging from 0.3 to 1.5 weight %; at least one carrier in an amount ranging from 74 to 91 weight %; and other pharmaceutically acceptable excipients, wherein the ratio of said mucinous extract of Abelmoschus esculentus to said carrier is in the range of 1:10 – 3:10. The present disclosure also provides a process for the preparation of the administration vehicle for oral pharmaceutical formulations.

Description

Title of the Invention

Administration Vehicle for Oral Pharmaceutical Formulations and Process of Preparation thereof.

Technical Field

The present disclosure in general relates to an administration vehicle for oral pharmaceutical formulations and a process of preparation thereof.

Background

Oral pharmaceutical formulations such as tablets and capsules can be difficult to administer or swallow, especially the big ones. Patients with chronic diseases like chronic kidney disease, diabetes mellitus, hypertension, tuberculosis, cancers etc. need to take multiple tablets for a prolonged duration. Further, the number of pills the patients need to take every day is high. Even further, it is often difficult to give medicines that are not available in the form of a syrup to small children and elderly people because of the risk of choking. Still further, many chronic kidney diseases and heart disease patients are advised to follow restriction of daily water intake and it is difficult for these patients to take large quantities of pills with a very small quantity of water. The afore-mentioned issues can significantly decrease the patient compliance in terms of consumption of medicines and following allied instructions. Consequently, the risk of complications due to the disease increases and so does the risk to the patient’s life.

Medicines in the form of pills (tablets, capsules and the like) are the mainstay in the treatment of patients with Chronic Kidney Disease (CKD). Kidney Disease Data Centre Study has reported the prevalence of CKD in India to be as high as 17%. 3 studies have estimated the prevalence of CKD in India as 800 per million population. Over one lakh new patients enter the renal replacement program annually. CKD management includes a multitude of goals such as: control of hypertension, control of diabetes mellitus, correction of electrolyte abnormalities, control of fluid balance with diuretics, correction of hypocalcemia, correction of hyperphosphatemia, correction of hyperparathyroidism, correction of metabolic acidosis, correction of anemia, treatment of urinary tract infections and other infections treatment of constipation , treatment of other co-morbid conditions like cardiovascular disease, cerebrovascular disease, malignancy and the like.

Consequently, an array of medicines needs to be consumed as a part of CKD management, which include Anti - hypertensives, Anti - diabetics, Diuretics, Sodium bicarbonate, Calcium supplements, Vitamin D supplements, Phosphate binders, Immunosuppressive drugs, Ketoanalogues, Kidney protective antioxidants, Kidney protective pre-probiotics, antacids, hypouricemic drugs, hypolipidemic drugs, multivitamins, laxatives, antibiotics for urinary tract infections and other infections, medicines for symptoms like nausea, cramps, pruritus, low appetite etc., medicines for other comorbidities like ischemic heart disease, cerebrovascular disease, autoimmune disease, malignancy etc.

It is therefore evident that the pill burden in CKD patients is very high. A CKD patient takes between 5 to 30 pills per day. There are numerous untoward consequences of such a tremendously high pill burden. Firstly, there is an increase in the liquid intake. The average water intake required to swallow 4-5 pills is at least 100-200ml. Daily water intake just for pill consumption - at least 400 to 1000ml per day. Most of the CKD patients are often advised to follow fluid restriction from 500ml to 1.5L per day. Many patients complain that they cannot follow fluid restriction because of high pill burden. Furthermore, there is a decreased patient compliance due to the size of the pills, the taste of the pills, the after-taste of the pills, difficulty in swallowing and even the fear of swallowing pills.

The present invention addresses the afore-mentioned concerns and provides an administration vehicle for oral pharmaceutical formulations and a process for preparation thereof. Objects

It is an object of the present disclosure to provide an administration vehicle for oral pharmaceutical formulations and a process for preparation thereof.

It is another object of the present disclosure to provide an administration vehicle for oral pharmaceutical formulations which facilitates easy swallowing of oral pharmaceutical formulations.

It is yet another object of the present disclosure to provide an administration vehicle for oral pharmaceutical formulations which facilitates easy swallowing of oral pharmaceutical formulations without additional supplementation with water.

It is another object of the present disclosure to provide an administration vehicle for oral pharmaceutical formulations which facilitates easy swallowing of oral pharmaceutical formulations for patients of all age groups.

It is another object of the present disclosure to provide an administration vehicle for oral pharmaceutical formulations which mitigates the problem of choking while swallowing of oral pharmaceutical formulations.

It is another object of the present disclosure to provide an administration vehicle for oral pharmaceutical formulations which increases patient compliance.

It is another object of the present disclosure to provide an administration vehicle for oral pharmaceutical formulations which is economical.

It is still another object of the present disclosure to provide a process for preparation of the administration vehicle for oral pharmaceutical formulations which is simple, cost and time effective.

Summary of Invention

The present disclosure relates to an administration vehicle for oral pharmaceutical formulations that comprises at least one mucinous extract of the plant Abelmoschus esculentus in an amount ranging from 9 to 24 weight %; at least one flavoring agent in an amount ranging from 0.3 to 1.5 weight %; at least one carrier in an amount ranging from 74 to 91 weight %; and other pharmaceutically acceptable excipients, wherein the ratio of said mucinous extract of Abelmoschus esculentus to said carrier is in the range of 1:10 - 3:10. The present disclosure also relates to a process for the preparation of the administration vehicle for oral pharmaceutical formulations.

Description

In accordance with a first aspect, the present disclosure provides an administration vehicle for oral pharmaceutical formulations.

The administration vehicle comprises at least one mucinous extract of the plant Abelmoschus esculentus in an amount ranging from 9 to 24 weight %, at least one flavoring agent in an amount ranging from 0.3 to 1.5 weight %, at least one carrier in an amount ranging from 74 to 91 weight % and other pharmaceutically acceptable excipients. It is a characteristic of the formulation of the administration vehicle that the ratio of the mucinous extract of Abelmoschus esculentus to the carrier is in the range of 1:10 - 3:10.

The extract of the plant Abelmoschus esculentus is the extract of the mucin of the fruit of Abelmoschus esculentus and is in an amount ranging from 9 to 24 weight %. The characteristic consistency of the mucin of Abelmoschus esculentus makes it a perfect candidate for use as an administration vehicle. Further, Abelmoschus esculentus is a well-tolerated, non-toxic vegetable with numerous beneficial effects. The inventors of the present disclosure propose using this mucinous extract as a vehicle to help patients swallow a large number of pills in one go, without the need to ingest any water to aid the swallowing. The slimy nature of the mucin facilitates swallowing of 5-6 pills with ease. Moreover, the contact of the pills with the mucin is not going to be for substantial amount of time, therefore any question of interaction of the mucin with the drugs in the pills does not arise. After ingestion, the mucin gets digested and the pills undergo absorption in the bloodstream and can initiate their therapeutic action. Thus, there is no probability of the pharmacokinetics of the medicine in the pills to be affected. The flavoring agent is at least one selected from the group consisting of the extract of Mentha arvensis, the extract of Citrus lemon and the extract of Vanilla planifolia and is included in an amount ranging from 0.3 to 1.5. In one embodiment, the flavoring agent is the extract of Mentha arvensis. The flavoring agent performs the function of providing a pleasant taste to the administration vehicle.

The carrier of the formulation of the present disclosure is at least one selected from the group consisting of filtered water, purified water, distilled water, double distilled water and saline solution and is present in an amount ranging from 74 to 91 weight %. The present formulation optionally comprises any other pharmaceutically acceptable excipient. It is a characteristic of the formulation of the administration vehicle of the present disclosure that the ratio of the mucinous extract of Abelmoschus esculentus to the carrier is in the range of 1:10 - 3:10. After extensive experimentation, the inventors of the present disclosure have observed that formulation gives the most optimum and efficient results when the two afore-stated ingredients are used in the following range 1:10 - 3:10.

In accordance with another aspect, the present disclosure provides a process for the preparation of the afore-mentioned administration vehicle for oral pharmaceutical formulations. The process comprises a series of steps as disclosed herein after.

As a first step, freshly chopped fruits of Abelmoschus esculentus, in an amount ranging from 9 to 24 weight %, are boiled in at least one carrier, in an amount ranging from 74 to 91 weight %, at a temperature of 100 degree C for a time period ranging from 20 to 35 minutes to form a mucinous liquid. Characteristically, the ratio of the mucinous extract of Abelmoschus esculentus to the carrier is maintained in the range of 1 : 10 - 3 : 10. In the second step, the boiling of the mucinous liquid is terminated and at least one flavoring agent is admixed there-to, in an amount ranging from 0.3 to 1.5 weight % to form a mucinous liquid admixture. In the third step, the mucinous liquid admixture is allowed to cool for a time period ranging from 20 minutes to 2 hours to form a cooled mucinous liquid admixture. In the last step, the cooled mucinous liquid admixture is strained to obtain the administration vehicle of the present disclosure.

The shelf life of the administration vehicle is up to 90 days when stored between 4- and 8-degree C. Storing the afore-stated administration vehicle in a regular refrigerator also works with the present formulation. Typically, a pre-determined quantity of the administration vehicle of the present disclosure is to be taken in a small cup made of any material such as plastic, metal and the like. Oral pharmaceutical formulations including but not limited to tablets, capsules, pills, granules and the like, 5-6 in number, are to be added in the administration vehicle. The vehicle is then consumed along with the pills and as a consequence, there is no need of consuming additional water to swallow the pills as the pills get swallowed with ease with the administration vehicle. In one embodiment, the pre-determined quantity of the administration vehicle to be taken with the oral pharmaceutical formulations is 15 ml.

The administration vehicle of the present disclosure has multiple advantage such as - it is a liquid product derived from natural sources, it is easy to prepare, pleasant to taste, has a pleasant flavour, can be stored between 4 and 8 degrees Celsius in a refrigerator for at least 3 months without altering the taste and the shelf life is good at room temperature with simple natural permitted preservative agent. The administration vehicle of the present disclosure has the following additional advantages: assists in swallowing of 5-6 pills in a volume of 10-15ml, swallowing of bigger tablets, capsules and soft-gelatin capsules will be smooth and easier, no perception of taste or after-taste of the pills, no perception of smell of the pills, no discomfort in the pharynx while swallowing the pills, no fear of swallowing pills, following fluid restriction becomes easy, decreased incidence of fluid overload, dyspnoea, oedema, pulmonary oedema in both dialysis and non-dialysis patients. This will further result in good compliance leading to slowing of progression of chronic kidney disease, reduced morbidity, reduced hospitalization, improved quality of life, useful in other conditions requiring fluid restriction such as congestive cardiac failure and left ventricular failure, ascites due to liver and other diseases, useful in other conditions where treatment involves very high pill burden like patients with multiple co-morbidities, useful in geriatric and pediatric patients where pill swallowing is a concern and also in the treatment of constipation where patients on fluid restriction frequently get constipation and are required to take regular laxatives. This product will help in relieving constipation. This demonstrates that the formulation of the present disclosure has tremendous synergistic effect. Further, in one embodiment, the estimated cost for preparation of 400mL ‘Abelmuschus Mucin Extract’ is INR 20. The administration vehicle of the present disclosure is therefore highly economical. The inventors of the present disclosure have carried out extensive experimentation to narrow down on the formulation of the present disclosure.

Determination of optimum quantity of carrier and flavouring agent: Experiment 1

Abelmoschus esculentus 50g was taken in a stainless steel vessel of 0.5L capacity. 100ml water was added to it. It was boiled for 10 min. The 100ml volume got reduced to 80ml due to evaporation. The resultant liquid was allowed to cool at room temperature. A mucinous liquid was formed. This liquid was used to swallow 2-3 pills at a time. The liquid however was more viscous than desired.

Testing:

The liquid was tested in 5 volunteers. The volunteers were asked to swallow pills with this liquid. 15ml liquid was taken in a small cup and pills were put in the liquid. The liquid was swallowed with the pills. The liquid was favorable for swallowing 2-3 pills but it was difficult to swallow more than 3 pills because of its viscous nature. Also 4 out of 5 volunteers did not like the typical taste and flavor of Abelmoschus esculentus.

Experiment 2

Abelmoschus esculentus 50g was taken in a stainless steel vessel of IL capacity. 1000ml water was added to it. It was boiled for 30min and allowed to cool for 2 hours. The 1000ml volume got reduced to 780ml due to evaporation. The resultant liquid was allowed to cool at room temperature. A mucinous liquid was formed. To mask the typical taste and flavour of Abelmoschus esculentus, 2.5ml of lemon juice was added to it. This liquid was used to swallow 2-3 pills at a time. The liquid however was less viscous than desired.

Testing:

The liquid was tested in 5 volunteers. The volunteers were asked to swallow pills with this liquid. 15mL liquid was taken in a small cup and pills were put in the liquid. The liquid was swallowed with the pills. The liquid was favourable for swallowing 2-3 pills. However, this liquid was too thin and so the volunteers experienced difficulty in swallowing more 5-6 pills at a time. As the liquid was more watery, the liquid got swallowed immediately and the pills (especially the bigger ones) in the liquid stayed behind in the mouth. So more liquid was required to swallow the pills. The volunteers noted that the sour taste due to lemon was not desirable either.

Experiment 3

Abelmoschus esculentus 100g was taken in a stainless steel vessel of 500mL capacity. 500mL water was added to it. It was boiled for 25min. The 500mL volume got reduced to 400mL due to evaporation. To mask the typical taste and flavour of Abelmoschus esculentus, Mentha avensis leaves, 5g, were added to it. The resultant liquid was allowed to cool for 2 hours at room temperature. A mucinous liquid was formed. This liquid was used to swallow 2-3 pills at a time. The viscosity of the liquid appeared to be just as desired.

Testing:

The liquid was tested in 10 volunteers. The volunteers were asked to swallow pills with this liquid. 15ml liquid was taken in a small cup and pills were put in the liquid. The liquid was swallowed with the pills. The liquid was favourable for swallowing 2- 3 pills. Volunteers appreciated the flavour of Mentha avensis. On the next day, same 10 volunteers were asked to swallow 5-6 pills with the liquid. All of them could swallow 5-6 pills in 15mL of this liquid with ease. The Mentha avensis flavour was found to be pleasant. The volunteers gave feedback that they found swallowing 5-6 pills with only small volume of the liquid very easy. They were able to swallow even bigger pills with ease. The strong smell and bitter taste of the pills also got masked because of this liquid. However, this liquid was too thin and so the volunteers experienced difficulty in swallowing more 5-6 pills at a time.

Determination of optimum quantity of Abelmoschus esculentus'.

Further experiments were carried out, on the lines on Example 1, 2 and 3. However, the quantity of water was fixed to 500 ml and the quantity of Abelmoschus esculentus was varied from 50 - 150 g. In the afore-mentioned example template, the quantity of

Abelmoschus esculentus was varied in 500 ml water

As demonstrated herein above, the inventors of the present disclosure have observed that formulation gives the most efficient results when Abelmoschus esculentus (g) and water are used in the following range 1:10 - 3:10. This is a characterizing feature of the present disclosure.

Determination of optimum quantity of Flavouring Agent:

Mentha avensis was finalized as the flavouring agent. Further experiments were carried out, on the lines on Example 1, 2 and 3. The quantity of water was fixed to 500 ml, the quantity of Abelmoschus esculentus was varied from 50 - 150 g and in each batch, Mentha avensis was added in quantities varying from 1 to 10 g. Please confirm.

% by weight calculation for the Flavouring Agent:

Optimization of Boiling time:

The experimentation format as given above was repeated and the ingredients and quantities giving optimum results were boiled for variable time periods.

Inference:

From the extensive experimentation indicated above, the inventors of the present disclosure inferred that the minimum quantity of Abelmoschus esculentus required for optimum consistency and ease of swallowing was 60g and the consequent maximum quantity was 120g. Similarly, the minimum quantity of Mentha avensis required for achieving the desired flavour was 2g and the consequent maximum was 8g. Further, the minimum boiling time required to achieve the optimum consistency and ease of swallowing was 20min and the consequent maximum was 35 min.

In one preferred embodiment, the administration vehicle of the present disclosure comprises 100g of fresh chopped fruits of Abelmoschus esculentus, 500mL water and 5g fresh leaves of Mentha arvensis. In one preferred embodiment, the process of preparing the administration vehicle for oral pharmaceutical formulations, comprises the following steps: boiling 100g of freshly chopped fruits of Abelmoschus esculentus in 500ml of drinking water for 25 minutes on medium flame to form a mucinous liquid; turning off the flame after 25 minutes followed by admixing 5g of fresh leaves of Mentha arvensis to form a mucinous liquid admixture; covering the mucinous liquid admixture and allowing it to cool for 1 hour, followed by straining the same to obtain the administration vehicle of the present disclosure in a quantity of approximately 400ml.

The embodiments described herein above are non-limiting. The foregoing descriptive matter is to be interpreted merely as an illustration of the concept of the present disclosure and it is in no way to be construed as a limitation. Description of terminologies, concepts and processes known to persons acquainted with technology has been avoided for the sake of brevity.

Technical Advantages and Economic Significance

The technical advantages and economic significance of the administration vehicle of the present disclosure and its process of preparation include but are not limited to:

• the formulation makes swallowing of pills easier,

• the formulation decreases the risk of choking due to big pills,

• the formulation facilitates pill swallowing in children and elderly individuals,

• the formulation facilitates pill swallowing with only small quantity of liquid in patients who are advised to follow strict restriction of liquid intake,

• the formulation will improve patient compliance, and

• the formulation will decrease complications like choking, fluid overload and those due to patient non-compliance.

Claims

We Claim:

1. An administration vehicle for oral pharmaceutical formulations comprising: a. at least one mucinous extract of the plant Abelmoschus esculentus in an amount ranging from 9 to 24 weight % ; b. at least one flavoring agent in an amount ranging from 0.3 to 1.5 weight %; c. at least one carrier in an amount ranging from 74 to 91 weight %; and d. other pharmaceutically acceptable excipients, wherein the ratio of said mucinous extract of Abelmoschus esculentus to said carrier is in the range of 1:10 - 3:10.

2. The formulation as claimed in claim 1, wherein said extract of the plant Abelmoschus esculentus is the extract of the mucin of the fruit of said plant.

3. The formulation as claimed in claim 1, wherein said flavoring agent is at least one selected from the group consisting of extract of Mentha arvensis, extract of Citrus lemon and extract of Vanilla planifolia.

4. The formulation as claimed in claim 1, wherein said carrier at least one selected from the group consisting of filtered water, purified water, distilled water, double distilled water and saline solution.

5. The formulation as claimed in claim 1 , wherein the shelf life of said administration vehicle is up to 90 days when stored between 4- and 8-degree C. A process for the preparation of an administration vehicle for oral pharmaceutical formulations; said process comprising: a. boiling freshly chopped fruits of Abelmoschus esculentus in an amount ranging from 9 to 24 weight % in at least one carrier in an amount ranging from 74 to 91 weight % at a temperature of 100 degree C for a time period ranging from 20 to 35 minutes to form a mucinous liquid; b. terminating the boiling and admixing at least one flavoring agent to said mucinous liquid in an amount ranging from 0.3 to 1.5 weight % to form a mucinous liquid admixture; c. allowing said mucinous liquid admixture to cool for a time period ranging from 20 minutes to 2 hours to form a cooled mucinous liquid admixture; and d. straining said cooled mucinous liquid admixture to obtain said administration vehicle for oral pharmaceutical formulations, wherein the ratio of said mucinous extract of Abelmoschus esculentus to said carrier is in the range of 1:10 - 3:10. The formulation as claimed in claim 1, wherein said flavoring agent is at least one selected from the group consisting of extract of Mentha arvensis, extract of Citrus lemon and extract of Vanilla planifolia. The formulation as claimed in claim 1, wherein said carrier vehicle at least one selected from the group consisting of filtered water, purified water, distilled water, double distilled water and saline solution.