INTRODUCTION:

In the ever-evolving tapestry of health and nutrition research, where the dance between nature's apothecary and the culinary arts unfolds, a modern renaissance is ignited. This revival unveils the latent potential of an expansive array of phytochemical compounds dwelling within the realms of both the edible and the esoteric, sparking a profound exploration of their prowess in combating maladies.

This dynamic synergy gives birth to the portmanteau "nutraceutical," a fusion of "nutrition," the essence of nourishing sustenance, and "pharmaceutical," the realm of therapeutic wonders.

Nutraceuticals, in their multifaceted splendour, emerge as consumable marvels or gastronomic creations endowed with the extraordinary ability to bestow health and medical benefits, standing as sentinels against a myriad of ailments.

At the core of our bodily symphony, foods and nutrients play a symphonic role as guardians of individual well-being, actively engaging in the reduction of risks associated with diverse diseases. Nutraceuticals, these medicinal victuals, take on the mantle of wellness stewards, sculpting immunity, and orchestrating the prevention and mitigation of specific maladies.

In the pharmaceutical arena, clinical testing is a stringent imperative, with animal trials acting as the litmus test for efficacy. Yet, the historical narrative of nutrition lacked such scrutiny. However, recent scientific revelations on food's impact on lifestyle-related diseases have cast a spotlight on this pivotal nexus¹.

Nutraceuticals, the vanguards of health, embody a holistic fusion of lipids, proteins, carbohydrates, vitamins, minerals, and other vital nutrients tailored to the specific focus of their intended use. This spectrum spans time-honored traditional foods and avant-garde non-traditional fare. When a nutraceutical supplement embarks on its journey within the body, it becomes part of intricate and precise digestion and absorption processes. Amidst a symphony of discontent with synthetic therapeutic agents and concerns about potential toxicities, the United States witnessed the advent of the "Dietary Supplements Health and Education Act" (DSHEA) in 1994, heralding a new era of regulatory oversight.

The essence behind nutraceutical dosage forms is to deliver tangible benefits by fortifying the body's supply of essential building blocks, operating on a dual front: alleviating disease signs and enhancing overall bodily performance.

Dr. Stephen L. DeFelice, the visionary founder of the Foundation of Innovation Medicine (FIM) in Crawford, New Jersey, bestowed upon the world the term "nutraceutical" in 1989, a clever amalgamation of "nutrition" and "pharmaceutical." This term, now ingrained in the lexicon of health and wellness, awaits a standardized regulatory definition.

In Canada, Health Canada paints a vivid picture of nutraceutical as meticulously isolated or purified products derived from foods, often taking medicinal forms not traditionally associated with everyday sustenance. These treasures, such as beta-carotene and lycopene, forge a bridge between nature's bounty and human health, embodying the delicate interplay between science and sustenance^1,2.

Diversifying Nutraceutical Classifications:

Nutraceutical, an expansive term encompassing products derived from food sources that offer supplementary health benefits beyond basic nutrition, reside in a realm where regulation is scant, leading to a wide array of applications and efficacy claims. The absence of a universally accepted definition has sparked calls, particularly within the medical community, for a more precise delineation of this category to distinguish among its diverse offerings. Indeed, a multitude of products can be classified under the nutraceutical umbrella³:

Dietary Supplements:

These products, often in the form of pills, are concentrated sources of nutrients derived from food. The Dietary Supplement Health and Education Act of 1994 provides a framework for what constitutes a dietary supplement, encompassing vitamins, minerals, herbs, amino acids, and more. Notably, dietary supplements do not require pre-approval by the FDA and often carry disclaimers regarding their intended use⁴.

Functional Foods:

These foods aim to enrich our diets with added health benefits, blurring the line between natural sustenance and dietary supplements. The practice of "nutrification" involves restoring nutrient content to pre-processing levels and, at times, introducing complementary nutrients. Functional foods, as defined by Health Canada, are ordinary foods with added components that confer specific medical or physiological benefits beyond mere nutrition. Japanese standards require that such foods be in their natural form, consumed regularly, and contribute to the regulation of biological processes to prevent or control diseases⁵.

Medical Foods:

Unlike over-the-counter products, medical foods are not available to consumers for self-use. The FDA designates them as formulations meant for the dietary management of diseases with recognized nutritional requirements, supervised and prescribed by healthcare professionals. Nutraceuticals and supplements differ from medical foods in meeting these distinctive criteria and undergoing stringent FDA oversight⁶.

Nutraceutical Advantages:

Nutraceuticals, in their multifaceted glory, bestow a treasure trove of health benefits, enhancing our well-being and elevating our quality of life. These benefits encompass:

· Enhanced overall health.

· Augmented energy levels.

· Alleviated anxiety.

· Improved mental clarity.

· Enhanced sleep quality and quantity.

· Disease prevention.

· Slowed aging process.

· Reinforced immune system.

· Increased life expectancy.

Capsules: Medicinal Marvels:

Capsules, those unit solid dosage forms, are small, gelatin-encased containers meticulously filled with measured drug substances. This Latin-derived term, "capsula," aptly describes these medicinal mini-vessels, occupying a significant role in the realm of drug development. Their prominence stems from the efficient manufacturing process that sets them apart from other dosage forms. Gelatin, renowned for its water-triggered disintegration property, remains the primary choice for capsule shells. Denatured gelatin, methyl cellulose, and polyvinyl alcohol can also be employed for this purpose. Capsules come in two primary types^7,8

Hard-shelled capsules:

These capsules encase dry, powdered ingredients or miniature pellets, sealed in two halves, a "body" and a "cap." Gelatin and plant polysaccharides serve as the gelling agents, while plasticizers like glycerine ensure the capsules' pliability.

Soft gelatin capsules:

Originally developed in the 19th century to mask the unpalatable aspects of drug substances, these capsules are versatile, serving pharmaceutical, health, nutrition, cosmetic, and even recreational purposes. They excel in areas such as line extension, uniformity of low-dose drugs, safety with potent compounds, and ease of consumption. The latest advances involve liquid and semisolid formulations to enhance bioavailability and reduce plasma variability^9,10.

Capsule Varieties:

Gelatin capsules:

These capsules, both soft and hard, constitute the foundation of capsule technology.

Soft gelatin capsules:

Leveraging strategic and technological advantages, soft gelatin capsules have become increasingly popular, finding applications across various domains.

Hard gelatin capsules:

The majority of capsule products are crafted from hard gelatin, known for its clear, tasteless, and colorless properties. However, it's worth noting that this material is of animal origin, bringing about stability and safety concerns due to its potential for transmissible spongiform encephalopathy (TSE)^11,12.

These capsules, both gelatinous and non-gelatinous, can be tailored to meet specific drug release profiles, coatings can be added for various purposes, and sustained release capsules are employed to optimize dosing schedules and maintain stable blood concentration levels.

In this ever-evolving landscape of health and nutrition, nutraceutical classifications continue to expand and evolve, offering a diverse array of options to enhance human well-being. Meanwhile, capsules stand as a reliable and adaptable medium for delivering various forms of medication, opening up a world of possibilities in the pharmaceutical industry^{13, 14}.

MATERIALS AND METHODS:

Materials:

Ingredients such as Liquorice Powder, Amla Powder, Fennel Powder procured from UK enterprises. were selected by comparing the COA. All ingredients used were of analytical grade^15,16

Preformulation Study’s:

Bulk Density: 25g of accurately weighed powder was poured into a graduated cylinder, powder bed was made uniform without disturbing the cylinder and the volume was measured directly from the graduation mark on the cylinder as ml. The volume measured was called as Bulk Volume and bulk density is calculated as -

Weight of powder

Bulk Density = -------------------------

Bulk Volume

Tapped Density:

After measuring bulk density same cylinder was set to measure tap density. The cylinder was tapped with 100 taps drop per min and operated for 500 taps. Volume was noted as Va tapping was done again for 750 times and final volume was noted as Vb. The difference between Va and Vb was calculated and when it was found to be not more than 2%, then Vb was considered as final tapped volume and tapped density was calculated by using following formula-

Weight of powder

Tapped Density = ---------------------------

Tapped Volume

Carr’s Index:

Carr’s Index of the powders was determined by using the formula.

Tapped density-Bulk density

Carr’s Index = ------------------------------------

Tapped Density

Hausner ratio:

Hausner ratio of the powders was determine by using the formula

Hausner’s ratio = (Tapped Density)/(Bulk Density)

Table 01: Carr’s Index & Hausner ratio

Carr’s Index (%)	Flow property	Hausner’s ratio
≤10	Excellent	1.00-1.11
11-15	Good	1.12-1.18
16-20	Fair	1.19-1.25
21-25	Passable	1.26-1.34
26-31	Poor	1.35-1.45
32-37	Very poor	1.46-1.59
>38	Very very poor	>1.60

Angle of repose:

To determine the angle of repose the powder was passed through the walls of funnel, fixed at a definite position. The powder was poured till the upper tip of the pile surface touched the lowermost end of the funnel and the angle of repose was calculated^{17, 18}.

Θ = tan^-¹ h/r

Where θ is the angle of repose, h is the height in cm, and r is the radius in cm.

Table 02: Acceptance criteria for angle of repose

Flow Property	Angle of Repose
Excellent	25-30
Good	31-35
Fair-aid not needed	36-40
Passable-may hang up	41-45
Poor-must agitate, vibrate	46-55
Very poor	56-65
Extremely poor	>66

Moisture Analysis:

The capsule blend was weighed, kept in an oven at 105℃ and equilibrated. It was reweighed again till 3 constant readings using moisture balance and moisture content was measured gravimetrically.

pH of capsule:

PH of 1% solution of the formulation was determined by means of a digital PH meter.

METHOD OF PREPARATION:

· Weigh accurately 75mg of amla and 75mg of liquorice for the formulation.

· Issue the apparatus required for formulation.

· The powders were triturated and passed through sieves to make it fine for capsule fillings.

· Then the direct filling was done in capsules with the help of capsule filling machine^19,20.

Hard Gelatin Capsule Filling Process:

Steps of hard gelatin capsule filling:

It goes without saying that the hard gelatin or hard shell gelatin capsule filling process is not possible without a machine. There is a wide array of equipment

available ranging from small scale manual filling to intermediate level, semi-automatic and fully automatic large-scale machines. They can also be hand-filled and compounding pharmacy is an example of that.

Powder Formulation Filling in Hard Gelatin Capsules:

Hard gelatin capsules can also be filled manually using hands for research purposes. Place the powder on a clean paper or porcelain plate and press the open end of the capsule downwards till the time it is filled. Now place the cap to close the capsules.

In any small-scale manufacturing unit, hard gelatin capsules are filled manually using a hand operated machine, Hand operated capsule filling machine come in a variety of capacities ranging from 24 to 300 capsules. You can also produce about 200 to 2000 capsules per hour by focusing a bit more on efficiency.

Large scale manufacturing units have a number of machines at their disposal. These machines are semi-automatic as well as automatic and you can expect huge production capacities ranging between 3000 to 1,50,000 per hour. You must know that in large scale units the filling process depends on one of these two dosing devices- dosing disk/tamping device or donator device^21,22.

Evaluation of Nutraceutical Capsules

Weight variation test: For hard capsules accurately weigh 10 capsules individually. Remove the contents of each capsule by suitable means. Accurately weigh

the emptied shells individually, and calculate for each capsule the net mass of its contents by subtracting the mass of the shell from the respective gross mass. Calculate the active substance content in each capsule from the mass of product removed from the individual capsules and the result of the assay²³.

The requirements are met if the acceptance value of 10 capsules is less than or equal to 15 percent. If acceptance value is greater than 15 percent, test the next 20 capsules and calculate the acceptance value. The requirements are met if the final acceptance value of the 30 capsules is less than or equal to 15 percent and no individual content of the capsule is less than (1-25 x 0.01) M or more than + 25 x 0.01) M in calculation of acceptance value under mass variation or content uniformity^24,25."

Weight of Capsule - Average Weight

Weight Variation = --------------------------------×100

Average Weight of capsule

Disintegration test:

To test for disintegration time, one capsule is placed in each tube and the basket rack is positioned in specified medium at 37±2°C such that capsule remains 2.5cm below the surface of the liquid on their upward movement and descend not closer than 2.5cm from the bottom of the beaker.

Perforated plastic discs may also be used in the test.

A standard motor driven device is used to move the basket assembly containing the capsules up and down through distance of 5 to 6cm at frequency of 28 to 32 cycles per minute.

The capsule complies with the test according to USP, if all of the capsules have disintegrated completely. If 1 or 2 capsules fail to disintegrate completely, repeat the test on 12 additional capsules. The requirement is met if not less than 16 of the totals of 18 capsules tested are disintegrated^26,27.

Table 03 Acceptance criteria for disintegration time of capsules

Capsules	Disintegration Time
Hard gelatin Capsules	30 minutes

RESULT:

Table 04 Phytochemical Screening of Liquorice

Sr.No	Phytoconstituents	Test Performed	Result
1	Carbohydrates	Molish’s test	-
2	Proteins	Copper Sulphate test	-
3	Flavonoids	Lead acetate test, NaOH solution test	+
4	Alkaloids	Dragendroff’s test	+
5	Steroids	Lieberman’s test	+
6	Terpenoids	Salkowski’s test	+
7	Saponins	Froth test	+
8	Tannins	Ferric chloride test	+
9	Phlobatannins	HCL test	-
10	Anthraquinones	Benzene test	-
11	Glycosides	Keller-Killani test	+
12	Phenolic Compounds	Ferric chloride test	-

Table 05 Phytochemical analysis of Amla

Sr. No	Phytoconstituents	Ethanolic extract of embilica officinalis
1.	Tannins	Present
2.	Flavanoids	Absent
3.	Alkaloid	Absent
4.	Terpenoid	Absent
5.	Glycoside	Absent
6.	Saponins	Absent
7.	Resin	Absent
8.	Carbohydrate	Present

Table 06 Result for Preliminary Tests of Amla^29,30,31

Sr. No.	Evaluation Parameters	Result	Acceptance Criteria
1.	Bulk Density	0.31g/ml	0.2 - 0.7g/ml
2.	Tapped Density	0.35g/ml	0.4 - 1.0g/ml
3.	Moisture Content	5.59%	Not more than 3%
4.	Total Ash Value	3.96% w/w	Not more than 5.0%
5.	Water soluble ash value	3.01% w/w	Not more than 40%
6.	Acid Insoluble ash value	0.71% w/w	Not more than 2.0%
7.	Carr’s Index	11%	11-15%
8.	Hausner’s Ratio	1.12	1.12-1.18
9.	Angle of repose	26.56 ^O	25-30
10.	PH	3.5	2.0 - 5.0

Table No 07 Disintegration Time of capsules:

Sr. No	Disintegration Time	Average Disintegration Time
1	3 min 20sec	4 min 10 sec
2	3 min 30sec
3	3 min 60sec

Acceptance criteria is 30 min.

6) Table No 08 Weight Variation Test:

0.250 - 0.24

= -- ---------------------------- ×100

0.248

= 0.80 %w/w.

Table No. 09 : Acceptance criteria of Weight Variation

Average Weight	Percent Difference
80 mg or less	10 %w/w
More than 80mg to 250mg	7.5%w/w
More than 250mg	5 %w/w

DISCUSSION:

In the initial stages of formulating our nutraceutical capsules, our journey began with the essential task of gathering foundational information and identifying the specific needs for the formulation. Nutraceuticals, a fusion of nutrition and pharmaceuticals, were our focus, aiming to provide health and medical benefits beyond basic nutrition. We recognized two primary types: functional foods and vitamins, minerals, and supplements (VMS). With a commitment to high standards, we delved into detailed literature reviews, meticulously understanding the nuances of different capsule types, their limitations, and the essential excipients required for the formulation. This groundwork paved the way for subsequent pre-formulation studies, wherein we delved into specific information on capsules and conducted crucial chemical and identification tests on selected drugs.

The qualitative phytochemical screening of the polyherbal extract provided intriguing insights, revealing the presence of alkaloids, flavonoids, tannins, cardiac glycosides, and phenolic compounds, all contributing to the therapeutic activity of our formulation. moving forward, we initiated the actual formulation using the direct powder filling method and a precision-driven capsule filling machine. This step required meticulous selection of chemicals and equipment to ensure the precision and efficacy of our capsules.

The evaluation parameters became a critical aspect, encompassing the weight variation test, uniformity of content, disintegration time, dissolution test, and moisture content. These parameters were instrumental in ensuring that our capsules met the highest quality standards. an exciting revelation in our journey was the advent of non-gelatin capsules, such as HPMC, PVA, and starch capsules, catering to various dietary restrictions and preferences. The significance of packaging emerged as a key consideration, with the primary goal being to prevent contamination and maintain optimal moisture levels during long-term storage. Our exploration encompassed various packaging options, including plastic blister packs, aluminum foil strips, and even glass, all designed to uphold the integrity of our capsules.

Challenges in long-term storage underscored the importance of meticulous temperature and humidity maintenance, essential for preserving the efficacy of our capsules over an extended period. in reflection, our nutraceutical capsule formulation journey proved to be a comprehensive process, ranging from the initial information gathering to the final stages of product quality control. The intersection of nutrition and pharmaceuticals in our formulation presented exciting possibilities, with advancements in capsule types and packaging continuously driving us toward the quest for better and more effective nutraceutical capsules. Staying abreast of the latest research and advancements in the field remains integral to our commitment to continual improvement.

CONCLUSION:

The study mentioned above leads us to the conclusion that our Formulated Nutraceutical capsules have yielded satisfactory and acceptable outcomes. Capsules offer numerous advantages for formulators, manufacturers, physicians, patients, and health-supplement consumers. These advantages can greatly enhance the chances of success for over-the-counter drug products and dietary supplements. The flow ability of a powder is directly influenced by both the physical properties of the material itself and the specific processing conditions in the handling system. Insufficient flow can result in wastage, machinery maintenance issues, and downtime, all of which incur additional costs. There are several test methods available for evaluating the flow behavior of powders, both before and after compression. Adhering to good manufacturing practices ensures a system that guarantees proper design, monitoring, and control of manufacturing processes and facilities. Compliance with these regulations ensures the identity, strength, quality, and purity of supplementary products by requiring manufacturers to effectively control their manufacturing operations. This includes implementing robust quality management systems, sourcing high-quality raw materials, establishing reliable operating procedures, investigating and addressing product quality deviations, and maintaining trustworthy testing laboratories. When effectively implemented at a nutraceutical company, this formal system of controls helps prevent instances of contamination, mix-ups, deviations, nutrient loss, failures, and errors. Consequently, it ensures that the Formulated Nutraceutical Capsules consistently meet their quality standards.

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Received on 24.02.2024 Modified on 22.05.2024

Res. J. Pharmacognosy and Phytochem. 2024; 16(3):159-164.

DOI: 10.52711/0975-4385.2024.00030