DE202023104492U1 - A system for producing a formulation for the treatment of hypertension, diabetic kidney disease and heart failure - Google Patents

Abstract

A system for producing a formulation for treating hypertension, diabetic kidney disease and heart failure, comprising:
a pre-formulation unit for carrying out pre-formulation studies on the drug enalapril maleate, the characterization being carried out by studying the organoleptic properties, loss on drying, solubility, melting point and distribution coefficient of the drug enalapril maleate;
an extraction unit for preparing or extracting jackfruit gum from powdered jackfruit, wherein extracted jackfruit gum is used together with the drug enalapril maleate to prepare the formulation; And
a formulation unit for producing a powder mixture of formulation and floating tablets using this powder mixture, the production of floating tablets being carried out using a direct compression process in which HPMC K15M superdisintegrants are used in different concentrations, thereby producing multiple formulations.

Description

FIELD OF THE INVENTION

The present disclosure relates to the field of pharmaceutical science and chemistry, providing a system for producing a formulation for treating hypertension, diabetic kidney disease and heart failure. Specifically, a novel formulation of enalapril maleate and Jack Fruit Gum, a herbal super-dissolving agent used to treat high blood pressure, diabetic kidney disease and heart failure.

BACKGROUND OF THE INVENTION

Enalapril is an angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure. It is a poorly soluble drug with a half-life of 11 hours and a bioavailability of 40%. The low bioavailability of enalapril is due to its first-pass metabolism in the liver.

To improve the bioavailability of enalapril, it is beneficial to develop a suspended drug delivery system that delays first-pass metabolism, increases gastric residence time, and releases the drug in the gastrointestinal tract where absorption of enalapril is more efficient.

There are a number of floating drug delivery systems designed for other drugs. These systems typically use a polymer that is less dense than stomach fluid, so the tablet floats on top of the liquid in the stomach. This prevents the tablet from being quickly emptied from the stomach, allowing the medicine to be absorbed over a longer period of time.

Therefore, there is a need for a floating matrix tablet formulation for the stomach which has a number of advantages over prior art systems, which formulation can be prepared using a combination of polymers allowing a more controlled release of the drug, and wherein The formulation can also be designed to have a specific buoyancy period so that the drug can be released into the gastrointestinal tract where absorption is more efficient.

From the foregoing discussion, it is clear that there is a need for a system for producing a formulation for the treatment of hypertension, diabetic kidney disease, and heart failure.

SUMMARY OF THE INVENTION

The present disclosure relates to a system for producing a formulation for treating hypertension, diabetic kidney disease and heart failure. In the present disclosure, a novel formulation is prepared with the drug enalapril maleate and jackfruit gum, a herbal superdissolving agent, to produce a floating tablet for the treatment of hypertension, diabetic kidney disease and heart failure. The aim of the present work is to produce enalapril tablet formulations with floating gastric matrix using different polymers. The composition of this formulation is selected to study the effect of various factors such as drug-polymer ratio and other parameters such as buoyancy time and release rate. The purpose of the present invention is to achieve better delivery of enalapril to the stomach and proximal parts of the small intestine by increasing the mean residence time (MRT) in the stomach. For this purpose, floating tablets are prepared to prolong gastric emptying, thereby delivering the maximum drug to the site of absorption. The formulation of enalapril maleate and jack fruit gum showed good results as an ideal gastric delivery system.

The aim of the present disclosure is to provide a system for producing a formulation for treating hypertension, diabetic kidney disease and heart failure. The system includes: a pre-formulation unit for carrying out pre-formulation studies on the drug enalapril maleate, where the characterization is carried out by studying the organoleptic properties, loss on drying, solubility, melting point and distribution coefficient of the drug enalapril maleate; an extraction unit for preparing or extracting jackfruit gum from powdered jackfruit, wherein extracted jackfruit gum is used together with the drug enalapril maleate to prepare the formulation; and a formulation unit for producing a powder mixture of formulation and floating tablets using this powder mixture, wherein the production of floating tablets is carried out using a direct compression method in which HPMC K15M superdisintegrants are used in different concentrations, thereby producing multiple formulations.

An object of the present disclosure is to provide a system for producing a formulation for treating hypertension, diabetic kidney disease and heart failure.

Another object of the present disclosure is to develop a new suitable formulation of enalapril maleate and jackfruit gum as a suitable packaging material for the treatment of hypertension, diabetic kidney disease and heart failure.

Another aim of the present disclosure is to use natural resources to produce the formulation in order to keep side effects as low as possible.

Another objective of the present disclosure is to evaluate the effects of various factors such as drug-polymer ratio and other parameters such as buoyancy time and release rate.

In order to further illustrate the advantages and features of the present disclosure, a more detailed description of the invention will be made with reference to specific embodiments thereof shown in the accompanying drawings. It is understood that these drawings represent only typical embodiments of the invention and are therefore not to be viewed as limiting its scope. The invention is described and explained in more detail and in greater detail with reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE FIGURES

• 1 veranschaulicht ein Blockdiagramm eines Systems zur Herstellung einer Formulierung zur Behandlung von Bluthochdruck, diabetischer Nierenerkrankung und Herzinsuffizienz gemäß einer Ausführungsform der vorliegenden Offenbarung;
• 2 veranschaulicht ein Arbeitsablaufdiagramm für die Zubereitung von Tabletten gemäß einer Ausführungsform der vorliegenden Offenbarung; Und
• 3A, 3B, 3C, 3D und 3E veranschaulichen Tabellen, die die Ergebnisse zeigen, die aus der Charakterisierung der hergestellten Formulierung und Tabletten gemäß einer Ausführungsform der vorliegenden Offenbarung erhalten wurden.

These and other features, aspects and advantages of the present disclosure will be better understood when the following detailed description is read with reference to the accompanying drawings, in which like reference numerals represent like parts throughout the drawings, in which:

• 1 illustrates a block diagram of a system for producing a formulation for treating hypertension, diabetic kidney disease and heart failure according to an embodiment of the present disclosure;
• 2 illustrates a workflow diagram for the preparation of tablets in accordance with an embodiment of the present disclosure; And
• 3A , 3B , 3C , 3D and 3E illustrate tables showing the results obtained from the characterization of the prepared formulation and tablets according to an embodiment of the present disclosure.

Additionally, experienced craftsmen will recognize that elements in the drawings are presented for convenience and may not necessarily have been drawn to scale. For example, the flowcharts illustrate the method through key steps that help improve understanding of aspects of the present disclosure. Additionally, in view of the construction of the device, one or more components of the device may have been represented in the drawings by conventional symbols, and the drawings may show only the specific details relevant to understanding the embodiments of the present disclosure around the drawings not to be obscured by details that would be readily apparent to one of ordinary skill in the art who would benefit from the description herein.

DETAILED DESCRIPTION:

In order to promote understanding of the principles of the invention, reference will now be made to the embodiment shown in the drawings and specific language will be used to describe the same. It is to be understood, however, that this is not intended to limit the scope of the invention, since changes and further modifications to the system illustrated and further applications of the principles of the invention set forth therein are contemplated as would normally occur to one skilled in the art Technology to which the invention relates.

Those skilled in the art will understand that the foregoing general description and the following detailed description are exemplary and illustrative of the invention and are not intended to limit the same.

References in this specification to “an aspect,” “another aspect,” or similar language mean that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure is included. Therefore, the phrases “in one embodiment,” “in another embodiment,” and similar phrases in this specification may, but not necessarily, refer to the same embodiment.

The terms “includes”, “comprising” or any other variations thereof are intended to cover non-exclusive inclusion so that a Process or method that includes a list of steps, not only includes those steps, but may not include other steps specifically listed or inherent in that process or method. Likewise, one or more devices or subsystems or elements or structures or components prefixed with "comprises...a" do not exclude, without further limitation, the existence of other devices or other subsystems or other elements or other structures from other components or additional devices or additional subsystems or additional elements or additional structures or additional components.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as generally understood by one of ordinary skill in the art to which this invention pertains. The system, methods and examples provided herein are for illustrative purposes only and are not intended to be limiting.

Embodiments of the present disclosure are described in detail below with reference to the accompanying drawings.

1 shows a block diagram of a system for producing a formulation for treating hypertension, diabetic kidney disease and heart failure according to an embodiment of the present disclosure. The system (100) comprises a pre-formulation unit (102) for carrying out pre-formulation studies for the drug enalapril maleate, the characterization being carried out by examining the organoleptic properties, loss on drying, solubility, melting point and distribution coefficient of the drug enalapril maleate.

In one embodiment, an extraction unit (104) is used to prepare or extract jackfruit gum from jackfruit powder form, wherein extracted jackfruit gum is used together with the drug enalapril maleate to prepare the formulation.

In one embodiment, a formulation unit (106) is used to produce a powder mixture of formulation and floating tablets using this powder mixture, the production of floating tablets being carried out using a direct compression process in which HPMC K15M superdisintegrants are used in different concentrations. This creates multiple formulations.

In one embodiment, an analytical analysis of the drug used, enalapril maleate, is carried out, with UV absorption maxima being determined by scanning the drug solution in phosphate buffer 6.8, 0.1 N HCL at a wavelength of 200-400 nm. 10 mg of enalapril maleate is accurately measured and then transferred to a 10 mL Erlenmeyer flask, which is then dissolved in sufficient methanol to reach a volume of 10 mL with methanol. A stock solution of 1 ml is then removed with a pipette and diluted to 10 ml with methanol and finally the spectrum is recorded in the range of 200-400 nm. An additional 10 mg of enalapril maleate is dissolved in 10 ml of phosphate buffer with a pH of 6.8 to create a standard curve, and then 1 ml of the stock solution is removed with a pipette and diluted to 5 ml of phosphate buffer with a pH of 6.8, and further dilution is carried out. Rinse with phosphate buffer pH 6.8 to obtain a solution in the concentration range of (0-14 µg/ml). To create a calibration curve of enalapril maleate in phosphate buffer pH 6.8, a stock solution is first prepared fresh by dissolving 10 mg of enalapril in 10 ml volumetric flasks. This solution is then filled up to the mark with phosphate buffer pH 6.8 to create a solution with a concentration of 1000 µg/ml, then 10 ml of this solution is diluted to 100 ml with phosphate buffer pH 6.8 to obtain a solution with a concentration of 100 µg/ml obtained, and now this second solution is used to prepare the required concentrations such as 2, 4, 6, 8, 10, 12, ad 14 µg / ml.

In one embodiment, to extract jackfruit gum, 100 g of powder is first soaked in 500 ml of distilled water and kept in a boiling water bath for 30 minutes with constant stirring and then left overnight, after which a gel forms. Stirred with 100 ml of water for 10 minutes and passed through a muslin cloth to obtain a slimy solution, to which an equal quantity of absolute alcohol is then added, resulting in a precipitate, which is then filtered through Whatman filter paper, then the precipitate is dried, and then gum is added 24 Kept in a desiccator for hours after drying the gum powder with a grinder and sifting through a No. 80 sieve. The powder finally obtained is reprecipitated and filtered to obtain a second portion. The cleaning is kept in the desiccator for 24 hours. The product obtained is packaged in an airtight container for further use.

In one embodiment, to prepare enalapril maleate floating tablets, a direct compression process is used in which all ingredients are mixed in a mortar and pestle for 5 minutes and then the mixture of all ingredients is pressed into tablets on a tablet press machine to produce tablets weighing 300 mg to form, using super explosives, HPMC K15M, in different concentrations. To prepare tablets, accurately weighed amounts of polymer and lactose or mannito are placed in a mortar and then mixed, to this the required amount of enalapril maleate is added and then further mixed, and then accurately measured amount of sodium bicarbonate is added with the medicine. Then the powder mixture is lubricated with magnesium stearate and talc and mixed for about 3 minutes. Finally, the resulting blend or mixture is compressed on a 16-station rotary tablet machine using a standard 10mm flat die.

In one embodiment, preformulation studies conducted may be described as a phase of the research and development process in which the formulation scientist characterizes the physical, chemical, and mechanical properties of new drug substances to develop stable, safe, and effective drug dosage forms. In this phase, the selection of new chemical entities to be used in the formulation process is done using the available data about the drug, e.g. B. physical and chemical data. The drug is characterized using various studies such as: B. organoleptic properties, loss on drying, solubility studies, melting point and distribution coefficient, all of which are listed below.

Organoleptic properties: The organoleptic properties of the drug such as color, smell, taste and appearance are crucial for identifying the sample and should be reported using descriptive terms.

Loss on Drying: Loss on drying is the weight loss as a percentage of weight caused by water and volatile solutions that can be driven off under certain conditions.

Solubility studies: It is crucial to understand the water solubility properties of a drug as they must have a certain degree of water solubility to produce a therapeutic effect. A saturated solution of the drug was prepared in a constant volume of phosphate buffers with pH 1.2, 6.8 and 7.4 and the resulting solutions were kept at room temperature for 24 hours while shaking periodically. The resulting solutions were filtered before subjecting them to UV spectrophotometry at a maximum wavelength of 212 nm for drug dissolution analysis.

Melting Point: By using a small amount of enalapril maleate in an instrument to determine the melting point and comparing it with standards, the capillary method was used to estimate the melting point of enalapril maleate.

Partition coefficient: In n-octanol, the distribution coefficient of enalapril maleate is calculated. Take 50 ml of n-octanol and 50 mg of precisely weighed medication, dissolve it in 50 ml of water and then pour the liquid into a separatory funnel. To achieve equilibrium, the mixture was shaken continuously for one hour and then left overnight. To test the absorption at 212 nm with a UV spectrophotometer, both phases were separated and the aqueous phase was filtered and diluted accordingly. The following formula was used to calculate the distribution coefficient: $${\text{P}}_{\text{o/w}}={\text{C}}_{\text{organic}}/{\text{C}}_{\text{w}\ddot{\text{a}}\text{ssrig}}$$

In one embodiment, absorption maxima of the drug are determined by conducting an analytical study, wherein a UV absorption maximum of the drug was determined by scanning the solution of the drug in phosphate buffer 6.8, 7.4, 0.1 N HCL at a wavelength of 200-400 nm. The detailed procedure for determining λ max in phosphate buffer pH 6.8 is described below.

10 mg of enalapril maleate was accurately weighed and transferred to a 10 mL Erlenmeyer flask. It was dissolved in a sufficient amount of methanol and the volume was made up to 10 ml with methanol. Exactly 1 ml of the stock solution was pipetted off and diluted to 10 ml with methanol. The spectrum was recorded in the range of 200-400 nm. A standard curve was prepared by dissolving 10 mg of enalapril maleate in 10 ml of phosphate buffer with pH 6.8. 1 ml is removed from the stock solution and diluted to 5 ml phosphate buffer pH 6.8. It was further diluted with phosphate buffer pH 6.8 to obtain a solution in the concentration range of (0-14 µg/ml). th. The absorption maximum for enalapril maleate was 212 nm.

To prepare a phosphate buffer with a pH of 6.8, dissolve 28.80 g of disodium hydrogen phosphate and 11.45 g of potassium dihydrogen phosphate in enough water to make 1000 ml.

The calibration curve of enalapril maleate in phosphate buffer pH 6.8 is prepared by first preparing a fresh stock solution by dissolving 10 mg of enalapril in a 10 ml volumetric flask. The solution is then filled up to the mark with phosphate buffer pH 6.8 to obtain the solution with a high concentration of 1000 µg/ml (strain I). 10 ml of this solution was diluted to 100 ml with phosphate buffer pH 6.8 to obtain a solution with a concentration of 100 µg / ml (stock solution II). The required concentrations of 2, 4, 6, 8, 10, 12 and 14 µg/ml are prepared from this secondary strain. The absorbance was measured at 212 nm with a UV spectrophotometer.

1. 1. 100 g Pulver wurden in 500 ml destilliertem Wasser eingeweicht und 30 Minuten lang unter ständigem Rühren über einem kochenden Wasserbad gehalten und über Nacht stehen gelassen.
2. 2. Dann wurde das gebildete Gel 10 Minuten lang mit etwa 100 ml Wasser gerührt und durch ein Musselintuch geleitet, um eine schleimige Lösung zu erhalten.
3. 3. Dann wurde der Schleimlösung die gleiche Menge absoluten Alkohols zugesetzt, was zur Ausfällung des Gummis führte, der durch Whatman- Filterpapier filtriert wurde.
4. 4. Der Niederschlag wurde auf einer Stahlplatte getrocknet und über Nacht in einem Ofen bei 40 °C aufbewahrt.
5. 5. Dann wird das Gummi 24 Stunden lang in einem Exsikkator aufbewahrt, nachdem das Gummipulver mit einer Mühle getrocknet und durch ein Sieb Nr. 80 gegeben wurde.
6. 6. Das erhaltene Pulver wurde erneut zur Umfällung verwendet und filtriert. Das erhaltene Pulver wurde im zweiten Teil der Reinigung 24 Stunden lang im Exsikkator aufbewahrt und in einem luftdichten Behälter verpackt und zur weiteren Verwendung im Exsikkator aufbewahrt.

In one embodiment, the extraction of jackfruit gum includes the following steps:

1. 1. 100 g of powder was soaked in 500 ml of distilled water and kept over a boiling water bath for 30 minutes with constant stirring and left overnight.
2. 2. Then the formed gel was stirred with about 100 ml of water for 10 minutes and passed through a muslin cloth to obtain a slimy solution.
3. 3. An equal amount of absolute alcohol was then added to the mucus solution, resulting in the precipitation of the gum, which was filtered through Whatman filter paper.
4. 4. The precipitate was dried on a steel plate and stored in an oven at 40 °C overnight.
5. 5. Then the gum is kept in a desiccator for 24 hours after drying the gum powder with a grinder and passing it through a No. 80 sieve.
6. 6. The powder obtained was used again for reprecipitation and filtered. The obtained powder was kept in the desiccator for 24 hours in the second part of purification and packed in an airtight container and stored in the desiccator for further use.

2 illustrates a workflow diagram for the preparation of tablets according to an embodiment of the present disclosure. The steps for preparing the mixture and tablets are described below.

Enalapril maleate floating tablets were prepared by direct compression according to the prepared formulation. The super explosive HPMC K15M was used in different concentrations. All ingredients were passed through sieve no. 40. All ingredients were mixed in a mortar and pestle for 5 minutes. The blended mixture was compressed into tablets on a tablet press machine to a weight of 300 mg.

1. 1. Die Mengen an Polymer und Laktose oder Mannit genau abwiegen, in einen Mörser geben und geometrisch vermischen.
2. 2. Zugabe der erforderlichen Menge Enalapril Maleat hinzufügen und mit einem Stößel vermischen.
3. 3. Zugabe einer genau abgewogenen Menge Natriumbicarbonat und anschließendes Mischen mit der Arzneimittelmischung.
4. 4. Schmieren Sie die Pulvermischung mit Magnesiumstearat und mischen Sie anschließend etwa 3 Minuten lang Talkum, um eine endgültige Mischung zu erhalten.
5. 5. Komprimieren der endgültigen Mischung auf einer 16-Stationen-Rotationstablettenmaschine mit 10-mm-Standard-Flachstanzern.

The steps to make tablets are listed below:

1. 1. Accurately weigh the amounts of polymer and lactose or mannitol, place in a mortar and mix geometrically.
2. 2. Add the required amount of Enalapril Maleate and mix with a pestle.
3. 3. Add an accurately measured amount of sodium bicarbonate and then mix with the drug mixture.
4. 4. Lubricate the powder mixture with magnesium stearate, then mix talc for about 3 minutes to obtain a final mixture.
5. 5. Compress the final mixture on a 16-station rotary tablet machine with standard 10mm flat punches.

In one embodiment, the prepared tablets were evaluated for weight uniformity, active ingredient content, hardness, thickness, friability, dissolution study, etc. In solid dosage form, the physicochemical properties of the mixture determine the tablet quality. If the mixing step is not properly optimized, it can affect the properties of the mixture and therefore the tablet produced. The mixture was characterized by the mass-volume ratio (bulk density, tap density, Hausner ratio, Carr index) and flow properties.

3A , 3B and 3C illustrate tables showing the results obtained from the characterization of the prepared formulation and tablets according to an embodiment of the present disclosure.

In one embodiment, the powder mixture produced is characterized by evaluating the angle of repose and the mass-volume relationship (bulk density, tap density, Hausner ratio, Carr index). The results of the characterization are in shown.

The angle of repose is the maximum angle of stable inclination, which is determined by friction, cohesion and the shapes of the particles. The internal angle between the surface of the stack and the horizontal surface is called the angle of repose and depends on the density, surface area and coefficient of friction of the raw material. The calculation of the angle of repose is shown below.

Wobei h = Höhe des Haufens, r = Radius des Haufens, θ = Böschungswinkel.The angle of repose was determined using the funnel method. The height of the hopper was adjusted so that the tip of the hopper just touched the pile of mixtures. The precisely weighed mixture was able to run freely on the surface through the funnel. The height and diameter of the powder cone were measured and the angle of repose was calculated using the following equation. $$\mathrm{\theta }=\tan -1\left(H/r\right)$$

Where h = height of the pile, r = radius of the pile, θ = angle of repose.

In one embodiment, to examine drug-excipient compatibility, Fourier transform infrared spectroscopy (FTIR) is performed, where the infrared spectra of the samples were obtained using an infrared spectrophotometer. Pure drugs, excipients and physical mixtures of drugs and excipients were subjected to FTIR study. The IR spectra were obtained using the KBr disk method. The results of FTIR spectroscopy are in shown.

In one embodiment, after producing tablets using direct compression, a post-compression analysis is performed in which post-compression parameters of the tablets such as weight fluctuation, hardness, drug content, friability, lag time and total floating time are evaluated. The results of the post-compression analysis are in shown.

1. 1. Auswertung der Gewichtsschwankung: Zufällig ausgewählte 20 Tabletten wurden einzeln und zusammen in einer Einzelschalenwaage gewogen. Das Durchschnittsgewicht wurde notiert und die Standardabweichung berechnet. Der IP-Grenzwert für die Gewichtsschwankung liegt bei Tabletten mit einem Gewicht von bis zu 120 mg bei ± 10 %, bei 120 mg bis 300 mg bei ± 7.5 % und bei mehr als 300 mg bei ± 5 %. $$\mathbf{PD}=\left(\mathbf{Wavg}\right)/\left(\mathbf{Winitial}\right)\times 100$$
   
   Dabei ist PD = prozentuale Abweichung , Wavg = Durchschnittsgewicht der Tabletten, Winitial = Anfangsgewicht der Tabletten.
2. 2. Härtebewertung: Mit diesem Test wird die Härte einer Tablette überprüft, die bei Lagerung, Transport und Handhabung abplatzen oder brechen kann. Dabei wurden sechs Tabletten nach dem Zufallsprinzip ausgewählt und die Härte jeder Tablette mit einem Monsanto-Härteprüfgerät gemessen. Die Härte wird üblicherweise in kg/cm2 gemessen.
3. 3. Tablettendicke und ihr Durchmesser: Die Tablettendicke sollte innerhalb von 5 % oder weniger eines Standardwerts liegen. Die meisten Tabletten haben einen einheitlichen Durchmesser, es sei denn, sie wurden mit unterschiedlichen Matrizen hergestellt. Kleine Unterschiede in der Tablettendicke und im Tablettendurchmesser wirken sich erheblich auf die Härte und das Auflösungsprofil der Tablette aus. Dicke und Durchmesser wurden mit einem Messschieber gemessen.
4. 4. Bröckeligkeit: Zur Bestimmung der Bröckeligkeit wurde der Roche Friabilator verwendet. Vorgewogene Tabletten wurden in einen Friabilator gegeben und 4 Minuten lang mit einer Geschwindigkeit von 25 U/min gedreht. Oder bis zu 100 Umdrehungen. Die Tabletten werden bei jeder Umdrehung aus einer Entfernung von 6 Zoll fallen gelassen. Die Tabletten wurden nach Entfernung der Feinstoffe erneut gewogen und der prozentuale Gewichtsverlust berechnet.
5. 5. Einheitlicher Inhalt: 10 Tabletten wurden zufällig ausgewählt und dann mit Mörser und Stößel gewogen und pulverisiert. Eine Pulvermenge entsprechend 50 mg wurde entnommen und in 100 ml Phosphatpuffer mit pH 6.8 gelöst. Von der obigen Arzneimittellösung wurde 1 ml entnommen und mit 9 ml Phosphatpuffer, pH 6.8, verdünnt. Anschließend wurde die Lösung mit Whatman -Filterpapier filtriert. Die Absorption der filtrierten Arzneimittellösung wurde mit einem UV-VIS-Spektrophotometer bei λmax 212 nm gemessen und der Arzneimittelgehalt bestimmt.
6. 6. Floating-Lag-Zeit: Die Zeit, die die Tablette benötigt, um an der Oberfläche der Flüssigkeit aufzutauchen, nachdem sie dem Auflösungsmedium bei pH 6.8, Temperatur 37 ± 0.5 °C und einer Paddelrotation mit 50 U/min hinzugefügt wurde.
7. 7. Gesamtschwimmzeit: Die Zeit, die die Tablette benötigt, um konstant auf der Oberfläche der Magenflüssigkeit zu schwimmen, bei pH 6.8, Temperatur 37 ± 0.5 °C, Paddelrotation bei 50 U/min.
8. 8. Auftriebs- oder Schwimmtest: Der In-vitro- Auftrieb wurde gemäß der Methode anhand der Schwimmverzögerungszeit bestimmt. Hier wurden die Tabletten in ein 100-ml-Becherglas mit Phosphatpuffer pH 6.8 gegeben. Die Zeit, die die Tablette benötigt, um an die Oberfläche zu steigen und zu schwimmen, wurde als Schwimmverzögerungszeit bestimmt und die Gesamtdauer, während der die Dosierungsform schwimmfähig bleibt, wird als Total Floating Time (TFT) bezeichnet.

How to perform this post-compression analysis is shown below.

1. 1. Evaluation of weight fluctuation: Randomly selected 20 tablets were weighed individually and together in a single pan scale. The average weight was recorded and the standard deviation was calculated. The IP limit for weight fluctuation is ± 10% for tablets weighing up to 120 mg, ± 7.5% for 120 mg to 300 mg, and ± 5% for more than 300 mg. $$\mathbf{P.D}=\left(\mathbf{Wavg}\right)/\left(\mathbf{Wininitial}\right)\times 100$$
   
   Where PD = percentage deviation, Wavg = average weight of the tablets, Winitial = initial weight of the tablets.
2. 2. Hardness Assessment: This test is used to check the hardness of a tablet that may chip or break during storage, transportation and handling. Six tablets were randomly selected and the hardness of each tablet was measured using a Monsanto hardness tester. Hardness is usually measured in kg/cm2.
3. 3. Tablet thickness and its diameter: The tablet thickness should be within 5% or less of a standard value. Most tablets have a uniform diameter unless they are made with different dies. Small differences in tablet thickness and diameter have a significant impact on the hardness and dissolution profile of the tablet. Thickness and diameter were measured with a caliper.
4. 4. Friability: The Roche Friabilator was used to determine friability. Preweighed tablets were placed in a friabilator and rotated at a speed of 25 rpm for 4 minutes. Or up to 100 revolutions. The tablets are dropped from a distance of 6 inches with each revolution. After the fines were removed, the tablets were weighed again and the percent weight loss was calculated.
5. 5. Uniform content: 10 tablets were randomly selected and then weighed and pulverized with mortar and pestle. A quantity of powder corresponding to 50 mg was removed and dissolved in 100 ml of phosphate buffer with pH 6.8. 1 ml of the above drug solution was taken and diluted with 9 ml of phosphate buffer, pH 6.8. The solution was then filtered with Whatman filter paper. The absorbance of the filtered drug solution was measured using a UV-VIS spectrophotometer at λmax 212 nm and the drug content was determined.
6. 6. Floating lag time: The time required for the tablet to float to the surface of the liquid after being added to the dissolution medium at pH 6.8, temperature 37 ± 0.5 °C and paddle rotation at 50 rpm.
7. 7. Total floating time: The time required for the tablet to constantly float on the surface of the gastric fluid, at pH 6.8, temperature 37 ± 0.5 °C, paddle rotation at 50 rpm.
8. 8. Buoyancy or swimming test: In vitro buoyancy was determined according to the swimming lag time method. Here the tablets were placed in a 100 ml beaker with phosphate buffer pH 6.8. The time required for the tablet to rise to the surface and float was determined as the floating lag time and the total time for which the dosage form remains buoyant is referred to as the total floating time (TFT).

The prepared floating tablets prolong gastric emptying, thereby delivering the maximum drug to the absorption site. The formulation of enalapril maleate and jack fruit gum showed good results as an ideal gastric delivery system.

The drawings and the description above provide examples of embodiments. Those skilled in the art will recognize that one or more of the elements described can certainly be combined into a single functional element. Alternatively, certain elements can be divided into several functional elements. Elements of one embodiment may be added to another embodiment. For example, the orders of the processes described herein may be changed and are not limited to the manner described herein. Additionally, the actions of a flowchart do not have to be implemented in the order shown; Not all actions necessarily have to be carried out. Even those actions that are not dependent on other actions can be carried out in parallel with the other actions. The scope of the embodiments is in no way limited by these specific examples. Numerous variations, whether explicitly stated in the specification or not, such as: B. Differences in structure, dimensions and material use are possible. The scope of the embodiments is at least as broad as indicated by the following claims.

Advantages, other benefits, and solutions to problems have been described above with respect to specific embodiments. However, the advantages, advantages, solutions to problems and any components that may cause a benefit, advantage or solution to occur or become more pronounced should not be construed as a critical, necessary or essential function or component of any or all of the claims.

CREDENTIALS

100

System for producing a formulation for the treatment of hypertension, diabetic kidney disease and heart failure.

102

Preformulation unit

104

Suction unit

106

Formulation unit

202

Accurately weigh the amounts of polymer and lactose or mannitol, place in a mortar and mix geometrically

204

Add the required amount of Enalapril Maleate and mix with a pestle

206

Add an accurately measured amount of sodium bicarbonate and then mix with the drug mixture

208

Lubricate the powder mixture with magnesium stearate and then mix talc for about 3 minutes to obtain a final mixture

210

Compressing the final mixture on a 16-station rotary tablet machine with standard 10mm flat punches

Claims (8)

A system for producing a formulation for the treatment of hypertension, diabetic kidney disease and heart failure, comprising: a preformulation unit for carrying out preformulation studies on the drug enalapril maleate, the characterization being carried out by studying the organoleptic properties, loss on drying, solubility, melting point and partition coefficient of the drug Enalapril maleate is done; an extraction unit for preparing or extracting jackfruit gum from powdered jackfruit, wherein extracted jackfruit gum is used together with the drug enalapril maleate to prepare the formulation; And a formulation unit for producing a powder mixture of formulation and floating tablets using this powder mixture, the production of floating tablets being carried out using a direct compression process, in which super disintegrant HPMC K15M in different concentrations can be used, producing multiple formulations. System after Claim 1 , wherein an analytical analysis of the drug used enalapril maleate is carried out, with UV absorption maxima being determined by scanning the drug solution in phosphate buffer 6.8, 0.1 N HCL at a wavelength of 200-400 nm. System after Claim 2 , wherein 10 mg of enalapril maleate is accurately measured and then transferred to a 10 mL Erlenmeyer flask, which is then dissolved in a sufficient amount of methanol to reach a volume of 10 mL with methanol, followed by a stock solution of 1 mL is removed with a pipette and diluted to 10 ml with methanol. The spectrum is then recorded in the range of 200-400 nm. System after Claim 3 , where another 10 mg of enalapril maleate is dissolved in 10 ml of phosphate buffer with a pH of 6.8 to create a standard curve, and then 1 ml of stock solution is removed with a pipette and diluted to 5 ml of phosphate buffer with a pH of 6.8, and further dilution is performed with phosphate buffer, pH 6.8, to obtain a solution in the concentration range of (0-14 µg/ml). System after Claim 4 , whereby to prepare a calibration curve of enalapril maleate in pH 6.8 phosphate buffer, first prepare a stock solution freshly by dissolving 10 mg of enalapril in 10 ml of a volumetric flask and then top up this solution to mark the mark using phosphate buffer pH 6.8 to obtain a solution with a concentration of 1000 µg/ml, then 10 ml of this solution is diluted to 100 ml with phosphate buffer pH 6.8 to obtain a solution with a concentration of 100 µg/ml and now this second solution is used to prepare required concentrations such as 2, 4, 6, 8, 10, 12 and 14 µg / ml are used. System after Claim 1 , whereby to extract jackfruit gum, 100 g of powder is first soaked in 500 ml of distilled water and kept on a boiling water bath for 30 minutes with constant stirring and then left overnight. Then the gel formed is stirred with 100 ml of water for 10 minutes and through passed over a muslin cloth to obtain a slimy solution, to which an equal quantity of absolute alcohol is then added, resulting in a precipitate which is then filtered through Whatman filter paper. The precipitate is then dried. The rubber is then kept in a desiccator for 24 hours, after drying the rubber powder using a mill and passing it through a No. 80 sieve, the final powder being reprecipitated and filtered to obtain a second part of the To obtain cleaning, the product obtained is kept in the drying cabinet for 24 hours and packed in an airtight container for further use. System after Claim 1 , wherein to prepare enalapril maleate floating tablets, a direct compression method is used, in which all ingredients are mixed in a mortar and pestle for 5 minutes and then the mixture of all ingredients is pressed into tablets on a tablet pressing machine to produce tablets weighing 300 mg form, using super explosives, HPMC K15M, in different concentrations. System after Claim 7 , wherein to prepare tablets, accurately weighed amounts of polymer and lactose or mannito are placed in a mortar and then mixed, to which the required amount of enalapril maleate is added and then further mixed and then accurately weighed. A quantity of sodium bicarbonate is added to the drug mixture, then the Powder mixture lubricated with magnesium stearate and talc and mixed for about 3 minutes, and finally the resulting mixture or blend is compressed on a 16 station rotary tablet machine using a 10mm standard flat hole punch.

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