WO2023246722A1

WO2023246722A1 - Dioscorea polystachya tablet formulation

Info

Publication number: WO2023246722A1
Application number: PCT/CN2023/101185
Authority: WO
Inventors: Wai Yip Thomas Lee
Original assignee: Aptorum Therapeutics Limited
Priority date: 2022-06-20
Filing date: 2023-06-20
Publication date: 2023-12-28

Abstract

A manufacturing method of Dioscorea polystachya Chinese yam powder tablets with a specified loading of 200-500 mg, the formulation to which the manufacturing method is applicable also allows direct compression manufacturing. The tablets produced have a controlled friability for achieving an optimal disintegration rate for controlled release of a non-hormonal bioactive ingredient to ensure therapeutic benefits.

Description

Dioscorea polystachya Tablet Formulation

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority from the U.S. provisional patent application number 63/353,639 filed June 20^th, 2022, and the disclosure of which is incorporated herein by reference in its entirety.

TECHNICAL FIELD

The present invention relates to a Dioscorea polystachya tablet formulation and manufacturing method thereof. More specifically, the present invention relates to the specific formulation and manufacturing for Dioscorea polystachya tablets having optimized disintegration characteristics to deliver maximum bioavailablity of the active ingredients in Dioscorea polystachya.

BACKGROUND

Menopausal symptoms occur when there is a decline in levels of estrogen and progesterone secreted by ovaries in women’s bodies as a natural aging process, which may include hot flushes, night sweaty, anxiety, panic, irritability and more; and menopause may also be a risk factor for osteoporosis. While hormone replacement therapy is the conventional medical treatment to relieve menopausal symptoms, such treatments may also cause side effects including an increase in risk of ovarian cancer, breast cancer and stroke.

Dioscorea polystachya, or Chinese yam is a species in the yam family well known and widely cultivated in Asia. Also known as Shan-yao or Huai-shan in Chinese, the Chinese yam, in particular the root tuber section, is frequently used as a homeopathic remedy, in particular Chinese medicine.

In Chinese medical theory, Chinese yam is known as an edible and medicinal herb for nourishing Yin, and may be used for the regulation of menstrual cycle. It has therefore been a practice in Chinese medicine to give prescriptions or medical formulations containing Chinese yam to menopausal women for relieving menopausal symptoms.

Recently, scientific literature has reported the therapeutic effect of Chinese yam extracts in improving the levels of sex hormones, lipids and antioxidants in women in menopause. It is also reported that a novel bioactive ingredient known as DOI, as extracted from Chinese yams, is effective in treating conditions resulting from low serum estrogen and progesterone levels, including osteoporosis and decline in cognitive abilities. There are also commercially available products which contain Chinese yam powders targeting menopausal women for the relief of menopausal symptoms.

However, the formulations of previous Chinese yam products do not lend themselves to fabrication by direct compression methods.

As the traditional granulation procedures used in the current products are associated with moisture and heat, and with the bioactive ingredients in the Chinese yam extracts having a potential moisture sensitivity and heat lability, direct compression method is a preferred method of tablet formulation for Chinese yam extracts due to a better maintenance of stability of the active ingredients throughout both the manufacturing process and the shelf life.

There is a need in the art for improved Dioscorea polystachya tablet formulation and manufacturing methods to increase bioavailability of the active ingredients. The present invention addresses this need.

SUMMARY OF THE INVENTION

The present inventors have determined that formulations of Dioscorea polystachya tablets using a direct compression process provide optimized disintegration characteristics to deliver maximum bioavailability.

Further, directly compressible formulations allow a single-step manufacturing process, in comparison to the traditional granulation-based formulations which may involve multiple steps including wet granulation, drying and milling, and effectively simplifies the manufacturing process by removing the intermediate steps, and thereby also minimizing the time and cost of production. This, in turn, more easily allows large-scale manufacturing.

With the aim of manufacturing tablets with a designated loading of Chinese yam powders in mind, the design of a compressible formulation is also crucial as it facilitates consistent and reliable dosing, resulting in better therapeutic outcomes.

In addition, directly compressible formulations in general have a higher flexibility in design, allowing a wider range of combinations of excipients and bioactive ingredients. Therefore, in the present invention aims to optimize the disintegration rate of the Chinese yam powder tablet for the controlled release of the active ingredients of the Chinese yam.

The formulation of the tablet and the manufacture method (compression force and pressure) are crucial factors in achieving the optimum disintegration rate of a tablet, both of which must be taken into careful consideration. Both processes have a major impact in varying tablet hardness, which is key in ensuring tablet integrity during handling and transportation. However excessive hardness negatively impacts the disintegration rates, and friability, which corresponds to faster disintegration rates leading to powder loss and reduced mechanical integrity.

In view of the above, a manufacturing method of a Chinese yam powder through a direct compression method, where the tablets with a specific loading of 200-500 mg and controlled friability for achieving an optimal disintegration rate for controlled release of a non-hormonal active ingredients to ensure therapeutic benefits is provided herewith. The method comprises providing an entire root tuber of an organic Chinese yam Dioscorea polystachya root; forming a powder from the Chinese yam root by drying and milling; mixing the Chinese yam root powder with a colorant to form a pre-blended first mixture; sieving the pre-blended first mixture to form a homogenously colored blend; mixing the pre-blended first mixture with a moisture absorbent in an amount of 0.1-0.2 %w/w to form a second mixture to maintain viability of an active ingredient and prevent humidity-based deterioration and to further maintain a friability of less than 1%in a formed tablet; combining the second mixture with a tablet binder to obtain a tablet cohesiveness such that a friability is less than 1%; further combining the second mixture with a superdisintegrant to cause the formed tablet to disintegrate in a controlled manner to impart bioavailability, the superdisintegrant being selected from one or more of a modified starch, a cross-linked polyvinylpyrrolidone or modified cellulose; adding a lubricant to the second mixture; homogenizing the second mixture to uniformly disperse all active ingredients, inactive ingredients and excipients, forming a third mixture; subjecting the mixture to direct compression with a tablet compressor for consistent and stable formation of tablets with uniform bulk density without involving any intermediate granulation processes, wherein the tablets formed have an average friability of less than 1%; average hardness of more than 7 kP and an average disintegration time of less than 45 minutes.

In an embodiment, the moisture absorbent is colloidal silicon dioxide.

In another embodiment, the tablet binder is microcrystalline cellulose.

In yet another embodiment, the superdisintegrant is sodium starch glycolate.

In yet other embodiment, the lubricant is magnesium stearate.

In a second aspect of the invention, the product Chinese Yam tablets manufactured under the aforementioned method is also provided herein, wherein the amount of Chinese Yam powder is 200-500 mg and is of an amount of 35-45 %w/w of the tablet; the fumed silica is colloidal silicon dioxide of an amount of 0.1-0.2 %w/w of the tablet; the tablet binder is microcrystalline cellulose of an amount of 56-57 %w/w of the tablet; the super-disintegrant is sodium starch glycolate of an amount of 2.5-3.5 %w/w of the tablet; and the flowing agent is magnesium stearate of an amount of 0.1-0.3 %w/w of the tablet.

In an embodiment, the tablets produced have an average hardness of 15.5-16.5 kP, and are manufactured under the turret speed of 25 RPM.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosure will become more fully understood from the detailed description given herein below for illustration only, and thus not limitative of the disclosure, wherein:

FIG. 1 is an albumin standard calibration curve obtained from the Chinese yam tablet sample, processed and subjected to colorimetric test at an absorbance of 562 nm.

FIG. 2 shows a sample TLC plate for identification testing of Chinese yam powder and the 375 mg Chinese yam tablets. Columns marked A are reference standard, B are Chinese yam powder, and C are Chinese yam tablets, 375 mg. The highest 2 of the 4 marked spots were selected as the test method acceptance criteria.

FIG. 3 is a schematic of the representative manufacturing process of the 375 mg Chinese yam tablets of the present invention.

DETAILED DESCRIPTION

In the following description, structures and methods of modification of the self-adhesive liquid silicone rubbers are set forth as preferred examples. It will be apparent to those skilled in the art that modifications, including additions and/or substitutions may be made without departing from the scope and spirit of the invention. Specific details may be omitted so as not to obscure the invention; however, the disclosure is written to enable one skilled in the art to practice the teachings herein without undue experimentation.

Various processes will be described below to provide an example of at least one embodiment of the claimed subject matter. No embodiment described below limits any claimed subject matter, and any claimed subject matter may cover processes or systems that differ from those described below. The claimed subject matter is not limited to processes or systems having all of the features of any process or system described below or to features common to multiple or all of the processes or systems described below. It is possible that a process or system described below is not an embodiment of any claimed subject matter. Any subject matter that is disclosed in a process or system described below that is not claimed in this document may be the subject matter of another protective instrument, for example, a continuing patent application, and the applicants, inventors, or owners do not intend to abandon, disclaim or dedicate to the public any such subject matter by its disclosure in this document.

Furthermore, it will be appreciated that for simplicity and clarity of illustration, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements. In addition, numerous specific details are set forth in order to provide a thorough understanding of the embodiments described herein. However, it will be understood by those of ordinary skill in the art that the embodiments described herein may be practised without these specific details. In other instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the embodiments described herein. Also, the description is not to be considered as limiting the scope of the embodiments described herein.

It should be noted that terms of degree such as “substantially” , “about” and “approximately” as used herein mean a reasonable amount of deviation of the modified term such that the end result is not significantly changed. These terms of degree may be construed as including a certain deviation of the modified term if this deviation would not negate the meaning of the term it modifies.

Furthermore, the recitation of numerical ranges by endpoints herein includes all numbers and fractions subsumed within that. It is also to be understood that all numbers and fractions thereof are presumed to be modified by the term “about” which means a variation up to a certain amount of the number to which reference is being made if the end result is not significantly changed.

As will be discussed in further detail below (in particular, the Examples section) , the present inventors determined a specific formulation that includes one or more disintegrants and excipients to achieve an optimum hardness, friability, and porosity such that a controlled disintegration is achieved. This optimum formulation and fabrication technique facilitates a more controlled release of the bioactive ingredient.

The inventors determined that the relationship between compression pressure and disintegration rate is crucial for maximizing beneficial effects. By carefully controlling the disintegration rate through formulation and manufacturing parameters, it is possible to achieve optimal release profiles and enhance the therapeutic efficacy of the Dioscorea polystachya. In particular, the inventors determined that when tablets have an average friability of 0.4%to 1.2%, an average hardness of 10-25 kP that an average disintegration time of less than 45 minutes can be achieved.

The present invention provides a manufacturing method of a Chinese yam powder through direct compression method. The tablets have a specific loading of 200-500 mg, and, in the examples below, a loading of 375 mg, with controlled friability for achieving an optimal disintegration rate for controlled release of a non-hormonal bioactive ingredient to ensure therapeutic benefits.

The method starts by providing an entire root tuber of an organic Chinese yam Dioscorea polystachya root and forming a powder from the Chinese yam root by drying and milling.

The Chinese Yam root powder is then mixed with a colorant to form a pre-blended first mixture. To ensure a uniform blend, the pre-blended mixture undergoes sieving, resulting in a homogenously colored blend.

To maintain the viability of the active ingredient and prevent humidity-based deterioration, the pre-blended first mixture is mixed with a moisture absorbent in an amount of 0.1-0.2%w/w. Colloidal silicon dioxide may be used as the moisture absorbent.

The second mixture, comprising the pre-blended mixture and moisture absorbent, is combined with a tablet binder to achieve tablet cohesiveness and ensure a friability of less than 1%in the formed tablet. Microcrystalline cellulose is an example of a suitable tablet binder.

Additionally, the second mixture is combined with a superdisintegrant, such as sodium starch glycolate, modified starch, cross-linked polyvinylpyrrolidone, or modified cellulose, to enable controlled disintegration of the tablet, thus imparting optimal bioavailability.

To aid in the compression process and facilitate the release of tablets from the tablet compressor, a lubricant, such as magnesium stearate, is added to the second mixture.

The resulting mixture, consisting of all active ingredients, inactive ingredients, and excipients, is homogenized to ensure the uniform dispersion of all components, forming a third mixture.

The third mixture is subjected to direct compression using a tablet compressor. This process allows for consistent and stable formation of tablets with uniform bulk density without involving any intermediate granulation processes. The tablets formed have an average friability of average friability of 0.4%to 1.2%, an average hardness of 10-25 kP that an average disintegration time of less than 45 minutes.

In an embodiment, the moisture absorbent is colloidal silicon dioxide.

In another embodiment, the tablet binder is microcrystalline cellulose.

In yet another embodiment, the superdisintegrant is sodium starch glycolate.

In yet other embodiment, the lubricant is magnesium stearate.

The current invention provides a manufacture method of 200-500 mg Chinese yam tablets developed, with the objectives of maximizing the bioavailability of the active ingredients in Chinese yam while achieving a smaller tablet size to improve compliance and maintain a reasonable level of strength; improving process efficiency through development of a directly compressible tablet for Chinese yam; improving tablet appearance and color uniformity by directly compressible blend for tableting; and achieving high efficiency of manufacturing while optimizing parameters such as lower friability, reasonable hardness and desired disintegration time.

EXAMPLES

In the Example section below, the optimum manufacturing method and formulation for the Chinese yam tablets of a loading of 375 mg in particular is discussed in detail. The proposed target product profile for the inventive Chinese Yam Tablets, 375 mg, is provided in Table 1 below:

Table 1. Target product profile for Chinese Yam Tablets, 375 mg

The materials used for the development of Chinese Yam Tablets, 375 mg, are provided in Table 2 below:

Table 2. Materials used in development of Chinese Yam Tablets, 375 mg

The qualitative compositions of the pigment blends are provided in Table 3 as tabulated below:

Table 3. Qualitative compositions of pigment blends

1. Analytical Method Development

1.1 Pierce BCA Protein Test Assay for Chinese Yam Tablets, 200-500 mg

Three blends of 2%colorant in a Chinese yam powder/MCC blend were produced for each of the three colorants (NB140000, NB140007 and PB140012) . The composition of the Chinese yam powder/MCC blend was as follows:

- 49.9%w/w of Chinese yam powder blend (96.74%w/w Chinese yam powder, 3.01%w/w Sodium Starch Glycolate (Explotab) and 0.25%w/w Colloidal Silicon Dioxide (Aerosil 200 Pharma) )

- 49.9%w/w of binder blend (97.0%w/w Microcrystalline Cellulose (Vivapur 102) , 3%w/w Explotab)

- 0.20%w/w of magnesium stearate

The protein contents of the three 2%colorant blends were quantified using the Pierce BCA protein assay.

A 3 g sample of Chinese Yam Tablets, 375 mg, was ground into fine powder by a mortar and pestle followed by the addition of 30 mL of water to the powder. The mixture was then incubated at 50℃ in a water bath for 30 min with stirring using a stir rod for roughly 20 s every 5 mins during incubation. The mixture was centrifuged (Beckman Coulter Allegra X-22) in a 10 mL centrifuge tube for 10 mins at 4,000 rpm. 100 μL of the supernatant was incubated with 2 mL of BCA reagent in a water bath at 37℃ for 30 mins. The sample was allowed to be cooled to room temperature and subsequently tested within 10 mins using the previously developed colorimetric method at 562 nm (Agilent 8453 UV-Vis) . The protein content was calculated using an albumin standard calibration curve as shown in Fig. 1.

The measured protein content (normalized to weight of sample) of samples stored for 2 weeks under accelerated storage conditions (40^oC/75%RH) was 1.98%, 1.91%and 1.49%for NB140000, NB140007 and PB140012 respectively.

However, the measured protein content met the requirements in the proposed specification, spectral shifts were detected for the 2%PB140012 blend suggesting that the assay values may be accurate, overestimated or underestimated. Spectral shifts were not detected in NB140000 and NB140007 blends.

The lead formulation (with 0.05%of colorant PB140012) and another formulation containing the same ingredients prior to addition of PB140012 were examined using Pierce BCA protein assay. The results showed no significant spectral shift at the target colorant (PB140012) concentration of 0.05%.

The lack of interference is further confirmed by the assay values where the protein content of the formulation with or without colorant at 0.05%w/w level were essentially the same at 1.64%and 1.76%respectively.

1.2 Identification of Yam Powder/Tablets by Thin-Layer Chromatography

A thin-layer chromatography (TLC) method was developed based on the validated procedure used for identification of Chinese yam powder in Chinese Yam Tablets, 375 mg. The method is described in Table 4:

Table 4. Identification by TLC for Chinese Yam Tablets, 375 mg

Identification by Thin Layer Chromatography (TLC) of tablets manufactured using the lead composition (containing PB140012 colorant) showed that that the key active ingredients of Chinese yam powder and are present in the 375 mg tablet formulation. The highest two of the four marked spots (R_f = 0.76 &0.67) , shown in Fig. 2, were selected as the acceptance criteria for identification testing.

2. Formulation and Process Development

2.1 Influence of Processing Procedure on Colorant Distribution in Tablets

In order to obtain even distribution of colorant in the tablets, both the choice of blending equipment and the comparison of direct colorant addition against colorant addition by way of a pre-blend were investigated.

The following blending equipment were experimented with:

- Low shear blender (PK Blend Master with 3.3 L v-shell)

- High shear blender (KG-5 High Shear Granulator with high-speed chopper)

- High shear blending equipment (Vitamix E320 food processor)

When adding the colorant to the blend, three approaches were tested:

- Direct addition of colorant to the excipients before mixing

- Mixing of colorant, binder blend and active blend using a high shear or low shear blender –the active and binder blend was produced separately using low shear blender

- Addition of colorant in binder pre-blend produced using high shear blender

For the first approach, all excipients (except magnesium stearate) were added to a v-shell blender with an Aerosil-Explotab pre-blend (prepared by bag mixing) . The colorant was then added and the contents were blended. For the second approach, active and binder blends were first manufactured separately. The active blend consisted of 96.74%w/w Chinese yam powder, 3.01%w/w Explotab and 0.25%w/w Aerosil and the binder blend consisted of 97.0%w/w MCC, 3%w/w Explotab) . Both active and binder blends were manufactured by low shear blender. The active blend, binder blend and colorant were added simultaneously to either a high shear or low shear blender and blended.

For the third approach, a pre-blend with colorant and Chinese yam powder was produced by bag mixing followed by sieving (20 mesh) . The colorant pre-blend was then added with the other ingredients (except for magnesium stearate) and an Aerosil-Explotab pre-blend (prepared by bag mixing) to a v shell blender and bended. In all three approaches, magnesium stearate was added and blended in at the end as a lubricant.

Adding colorant to the final blend using a KG-5 high shear mixer (pilot scale) resulted in a homogenous blend and tablets. Since using a full-scale high shear mixer was impractical for commercial manufacture at this stage, this approach was not adopted.

A pre-blend of a colorant and Chinese yam powder was bag mixed and sieved through a 20-mesh sieve. The pre-blend was then mixed with the rest of the materials using a v-blender. This resulted in a homogenously colored blend and tablets suggesting that sieving of pre-blends is effective in deagglomerating and dispersing the colorant in the tablets manufactured. Hence, the sieved pre-blend approach was selected as the processing procedure to ensure the homogenous distribution of colorant in the product.

The compositions tested are described in Table 5.

Table 5. Composition of Chinese Yam Tablet, 375 mg, evaluated for colorant homogeneity studies
*Yam blend consist of 96.74%w/w Yam powder, 3.01%w/w Explotab and 0.25%w/w Aerosil. Binder blend
consists of 97.0%w/w MCC, 3%w/w Explotab.
**For these blends a high shear blender was used

Note: NT = Not Tested

2.2 Influence of Tooling Design on Tablet Disintegration

Development batches were manufactured using a Piccola Bilayer Tablet Press (rotary press) and two different sets of tooling (both manufactured by Natoli Engineering Co. ) The tooling dimensions are:

- 19.5 mm × 9.2 mm with cup volume of 95.94 mm³ (Tooling A)

- 18 mm × 8.3 mm with cup volume of 108.32 mm³ (Tooling B)

Tooling B has greater convexity in comparison to Tooling A (i.e. Tooling A produces less convex tablets) .

Tablets of the same composition prepared using Tooling A are less convex and exhibit better disintegration times than those prepared using Tooling B. The results can be explained by more even distribution of compression force during tableting, resulting in more uniform bulk density in each tablet.

The results are tabulated in Table 6.

Table 6. Influence of blend composition and tooling on disintegration, friability and hardness of Chinese Yam Tablets, 375 mg

Note: NT = Not Tested

2.3 Influence of Tablet Composition on Tablet Disintegration

Different target weight and blend compositions were tested while keeping the Chinese yam powder content at 375 mg/tablet. Raising tablet binder (i.e. MCC) content to facilitate disintegration required a higher target compression weight to maintain 375 mg/tablet of Chinese yam powder.

In addition, properties of Chinese yam tablets prepared using the following compositions of pre-blend were evaluated:

- Chinese yam powder with Explotab and Aerosil

- Chinese yam powder added to a pre-blend of MCC with Explotab

- Chinese yam powder added to a pre-blend of Explotab and Aerosil

The tablet samples were evaluated for disintegration, weight, hardness, and friability.

Samples with the same yam to binder ratio as the previously developed 750 mg tablets did not achieve the target disintegration time (≤ 45 min) when directly blended and compressed.

Reduction in tablet hardness improved disintegration time, but the tablet friability target of ≤1%was not achieved.

Increase in binder blend (97.0%w/w MCC and 3%w/w Explotab) relative to yam blend improved the disintegration time. Therefore, the active loading in tablet was decreased, by increasing the target compression weight (see Table 7 below) . A tablet with 937.6 mg target weight and 40%w/w of Chinese yam powder was selected based on disintegration and friability test results (see Table 6 above) .

Table 7. Influence of binder levels and compression hardness on disintegration time and friability for Chinese Yam Tablets, 375 mg
*Yam blend consist of 96.74%w/w Chinese yam powder, 3.01%w/w Explotab and 0.25%w/w Aerosil
**Binder blend consists of 97.0%w/w MCC, 3%w/w Explotab

NT = Not Tested

2.4 Influence of Compression Force/Tablet Hardness on Tablet Disintegration

Based on the tablet composition studies, a lead tablet blend composition and blending process involving a sieved pre-blend of colorant and Aerosil was identified, prepared, and studied. The lead composition is provided in Table 8.

Table 8. Lead composition for Chinese Yam Tablets, 375 mg

Trials were conducted based on the lead composition to study the effects of different levels of tablet hardness (achieved by changing the compression force) on disintegration. Trials were also conducted using the lead tablet blend composition to determine the effects of compression speed on tablet hardness and rate of disintegration.

The tablets produced for disintegration testing had of a mean hardness of 13 to 21.5 kP and were manufactured at turret speeds ranging from 15 to 25 rpm. The tablet hardness was also correlated with improved visual appearance and proportional to disintegration time. The faster turret speed also produced faster disintegrating tablets. A tablet hardness of approximately 16 kP produced at 25 rpm was observed to have a reliable disintegration rate and acceptable visual appearance.

The results are tabulated in Table 9 below.

Table 9. Influence of compression speed and force (tablet hardness) on disintegration time of Chinese Yam Tablets, 375 mg (lead tablet blend composition)

Note: NT = Not Tested

Therefore, based on the experiments conducted, the following direct compression manufacturing process was developed for Chinese Yam Tablets, 375 mg, as illustrated in Fig. 3.

INDUSTRIAL APPLICABILITY

The present invention is applicable in stable manufacturing of direct compression tablets with a specific Chinese yam powder loading of 200-500 mg with highly desirable parameters for achieving an optimal disintegration rate for controlled release of a non-hormonal bioactive ingredient to ensure therapeutic benefits.

Claims

A method for manufacturing Dioscorea polystachya Chinese Yam tablets through direct compression method, the tablets having a specific loading of 200-500 mg, controlled friability for achieving an optimal disintegration rate for controlled release of a non-hormonal bioactive ingredient to ensure therapeutic benefits, wherein the method comprises:

providing an entire root tuber of an organic Chinese yam Dioscorea polystachya root;

forming a powder from the Chinese yam root by drying and milling;

mixing the Chinese yam root powder with a colorant to form a pre-blended first mixture;

sieving the pre-blended first mixture to form a homogenously colored blend;

mixing the pre-blended first mixture with a moisture absorbent in an amount of 0.1-0.2 %w/w to form a second mixture to maintain viability of an active ingredient and prevent humidity-based deterioration and to further maintain a friability of less than 1%in a formed tablet;

combining the second mixture with a tablet binder to obtain a tablet cohesiveness such that a friability is less than 1%;

further combining the second mixture with a superdisintegrant to cause the formed tablet to disintegrate in a controlled manner to impart bioavailability, the superdisintegrant being selected from one or more of a modified starch, a cross-linked polyvinylpyrrolidone or modified cellulose;

adding a lubricant to the second mixture;

homogenizing the second mixture to uniformly disperse all active ingredients, inactive ingredients and excipients, forming a third mixture;

subjecting the mixture to direct compression with a tablet compressor for consistent and stable formation of tablets with uniform bulk density without involving any intermediate granulation processes, wherein the tablets formed have an average friability of less than 1%; average hardness of more than 7 kP and an average disintegration time of less than 45 minutes.
The method of claim 1, wherein the moisture absorbent is colloidal silicon dioxide.
The method of claim 1, wherein the tablet binder is microcrystalline cellulose.
The method of claim 1, wherein the superdisintegrant is sodium starch glycolate.
The method of claim 1, wherein the lubricant is magnesium stearate.
The method of claim 1, wherein:

the amount of Chinese Yam powder is of an amount of 35-45 %w/w of the tablet;

the desiccant is colloidal silicon dioxide of an amount of 0.1-0.2 %w/w of the tablet;

the tablet binder is microcrystalline cellulose of an amount of 56-57 %w/w of the tablet;

the superdisintegrant is sodium starch glycolate of an amount of 2.5-3.5 %w/w of the tablet; and

the lubricant is magnesium stearate of an amount of 0.1-0.3 %w/w of the tablet.
The method of claim 1, wherein the tablets produced have an average hardness of 15.5-16.5 kP and are manufactured under the turret speed of 25 RPM.
A Dioscorea polystachya Chinese Yam tablet manufactured in accordance with the method of claim 6.