Formulation and Evaluation of Colon-Targeted Wheat Grass Tablets Using pH-Dependent Mechanism

The oral route is the most preferred method of drug administration due to its convenience, safety, and patient compliance. However, conventional oral drug delivery systems often fail to deliver the required amount of drug specifically to the intended site of action within the gastrointestinal tract. Drugs administered orally may undergo degradation in the acidic environment of the stomach or enzymatic breakdown in the upper intestine, resulting in reduced therapeutic efficiency and increased systemic side effects. Colon-targeted drug delivery systems are specially designed to transport therapeutic agents intact through the stomach and small intestine and release them selectively in the colon. Such systems are particularly useful for drugs that are unstable in upper gastrointestinal conditions, poorly absorbed in the small intestine, or intended for local action in the colonic region. The colon provides unique physiological conditions that make it an attractive site for targeted drug delivery. These include a relatively neutral pH, longer transit time, lower enzymatic activity compared to the upper gastrointestinal tract, and the presence of abundant microflora capable of metabolizing certain polymers. Exploiting these characteristics allows the development of formulations that release drugs specifically in the colon.

Approaches for Colon-Targeted Drug Delivery

Various strategies have been developed to achieve colon-specific drug release. These include:

1. pH-Dependent Systems

These systems utilize polymers that remain intact in the acidic pH of the stomach but dissolve at the higher pH found in the colon. Drug release occurs when the formulation encounters the appropriate pH environment.

2. Time-Dependent Systems

In this approach, drug release is delayed for a predetermined lag time corresponding to the transit time from the stomach to the colon.

3. Microflora-Activated Systems

These systems depend on the enzymatic activity of colonic bacteria to degrade specific biodegradable polymers, thereby releasing the drug in the colon.

4. Pressure-Controlled Systems

Drug release is triggered by the increased luminal pressure present in the colon. Among these methods, pH-sensitive systems are widely employed due to their simplicity, reproducibility, and effectiveness.

pH-Dependent Tablets

pH-dependent tablets are oral dosage forms specially designed to release the drug at a particular pH level within the gastrointestinal tract. Different parts of the digestive system have different pH conditions. The stomach is highly acidic, with a pH of about 1–3, whereas the small intestine and colon have a higher and more alkaline pH, usually between 6 and 8. These tablets utilize this variation in pH to ensure that the drug is released only at the desired site. These tablets are coated with pH-sensitive polymers that remain intact in acidic environments but dissolve when exposed to alkaline conditions. As a result, the tablet does not release the drug in the stomach but begins releasing it when it reaches the intestine or colon, where the pH is higher. Commonly used pH-sensitive polymers include Eudragit, cellulose acetate phthalate, and hydroxypropyl methylcellulose phthalate. pH-dependent tablets are especially useful in treating diseases that affect specific regions of the gastrointestinal tract, such as ulcerative colitis. In such conditions, the drug is released directly in the colon, which improves therapeutic effectiveness at the target site and minimizes unwanted side effects in other parts of the body.

Role of Eudragit Polymers in Colon Targeting

Eudragit polymers are synthetic methacrylate-based polymers extensively used in controlled and site-specific drug delivery. They are available in various grades with distinct solubility profiles, enabling selective drug release at specific pH values. pH-responsive Eudragit polymers remain stable in acidic gastric conditions and dissolve at higher intestinal or colonic pH levels. This property makes them particularly suitable for colon-targeted formulations. These polymers provide protective coatings around tablets, preventing premature drug release and ensuring delivery to the desired site. Their stability, reproducibility, and regulatory acceptance have made Eudragit polymers a preferred choice for colon-specific drug delivery systems.

Herbal Drugs and the Need for Targeted Delivery

Herbal medicines contain multiple bioactive constituents that exhibit antioxidant, anti-inflammatory, antimicrobial, and immunomodulatory properties. However, many herbal compounds suffer from poor stability, low bioavailability, and degradation in the upper gastrointestinal tract. Incorporating herbal extracts into colon-targeted delivery systems enhances their stability and therapeutic potential. By protecting active constituents from gastric and intestinal degradation, targeted systems improve local availability and overall efficacy.

Wheat Grass (Triticum aestivum): Therapeutic Potential

Wheat grass refers to the young shoots of the wheat plant (Triticum aestivum). It is rich in chlorophyll, vitamins, minerals, amino acids, enzymes, and flavonoids. Traditionally, it has been consumed as a nutritional supplement for detoxification, immune support, and digestive health. Scientific investigations have demonstrated that wheat grass possesses strong antioxidant and anti-inflammatory activities. Chlorophyll, one of its major components, plays a significant role in neutralizing free radicals and supporting tissue repair. Despite its therapeutic benefits, conventional oral administration may lead to partial degradation of its active constituents before reaching the colon. Therefore, developing a colon-targeted formulation can enhance its effectiveness.

Need for Wheat Grass Tablets as a Colon-Targeted System

Tablets are one of the most commonly used oral dosage forms due to their convenience, accurate dosing, stability, and patient acceptability. Formulating wheat grass into tablet form allows standardized dosing and improved shelf life. By coating wheat grass tablets with pH-sensitive polymers such as Eudragit, the formulation can be designed to resist the acidic gastric environment and release the active components selectively in the colon. This approach enhances localized therapeutic action while minimizing systemic exposure. Colon-targeted wheat grass tablets represent a novel integration of herbal therapy with advanced pharmaceutical technology, aiming to improve drug stability, efficacy, and patient compliance.

MATERIALS:

Drug

Wheat Grass Powder (dried and finely powdered young shoots of Triticum aestivum)

Excipients

The following pharmaceutical excipients were used in the formulation of wheat grass tablets:

1. Microcrystalline Cellulose (MCC) – Used as a diluent and dry binder to improve compressibility and tablet strength.
2. Lactose Monohydrate – Employed as a filler to achieve the desired tablet weight and enhance uniformity.
3. Sodium Starch Glycolate – Added as a superdisintegrant to facilitate rapid tablet disintegration when required.
4. Hydroxy Propyl Methyl Cellulose (HPMC) – Utilized as a binder and film-forming agent in the formulation.
5. Talc – Used as a glidant to improve powder flow during tablet compression.
6. Magnesium Stearate – Incorporated as a lubricant to prevent sticking of powder to punches and dies.
7. Methyl Paraben – Added as a preservative to enhance formulation stability.
8. Eudragit S – A pH-sensitive polymer used for coating to ensure drug release in the colonic region.
9. Eudragit L – A methacrylate-based polymer used in combination with Eudragit S for targeted drug delivery.
10. Glycerin – Used as a plasticizer in the coating solution to provide flexibility to the polymer film.
11. Ethanol – Used as a solvent for preparing the coating solution.

METHODOLOGY:

Tablet Preparation Procedure:

Material Sieving: Weigh precise quantities of wheat grass powder, microcrystalline cellulose, lactose monohydrate, sodium starch glycolate, hydroxypropyl methylcellulose, talc stearate, magnesium stearate, and methyl paraben. Sieve all individually using a 40-60 mesh screen to standardize particle size and break clumps.

Primary Mixing: Merge the sieved wheat grass powder, microcrystalline cellulose, and lactose monohydrate in a sanitized dry blender or mortar. Mix steadily for 5-10 minutes until a consistent powder mass forms.

Disintegrant and Binder Addition: Fold in sodium starch glycolate and hydroxypropyl methylcellulose to the initial blend. Continue mixing for 5 additional minutes to promote uniform dispersal for effective tablet breakup and cohesion.

Glidant and Lubricant Integration: Introduce talc stearate as glidant, magnesium stearate as lubricant, and methyl paraben as preservative in stages. Blend the full combination for 10-15 minutes overall, verifying uniformity through sight or sampling.

Blend Characterization: Test powder attributes like bulk and tapped densities (target Hausner ratio below 1.25), repose angle under 30 degrees, and compressibility below 20 percent to ensure suitable handling.

Compression Process: Transfer the blend to a tablet punching machine (manual or rotary type). Apply 4-6 kN pressure to form tablets weighing around 400 mg.

Coating Procedure:

Ethanol (90 mL) was taken in a clean, dry beaker and the required amount of Eudragit polymer was added slowly with continuous stirring until completely dissolved. Glycerin (0.5 mL) was added as a plasticizer, followed by talc (0.2 g) dispersed in a small amount of ethanol. The solution was stirred until a uniform and lump-free coating solution was formed and then filtered. Each tablet was held with forceps and dipped into the coating solution for 2–3 seconds, then removed and allowed to drain. The coated tablets were first air-dried for about 5 minutes and then dried in a hot air oven at 40–45°C for 10 minutes. This dipping and drying process was repeated 4–6 times until the desired coating thickness was achieved.

RESULTS AND DISCUSSION:

Precompression Parameters:

Bulk Density:

Measure weight of powder in a 100 mL cylinder at initial volume. Value obtained: 0.47 g/mL, showing reasonable space utilization in the blend.

Tapped Density:

Subject cylinder to 500 taps until volume settles. Recorded: 0.57 g/mL, demonstrating enhanced settling under mechanical agitation.

Compressibility Index Derived from [(Tapped - Bulk density)/Tapped density] × 100.

Finding: 17.54%, rated as fair-to-good (under 20% ideal), supporting smooth machine feed.

Hausner Ratio:

Outcome: 1.20, indicating low interparticle friction suitable for direct compression processes.

Angle of Repose:

Determine via fixed funnel method: tan?¹(h/r). Achieved: 27.9°, signifying free-flowing characteristics (<30° threshold).

Post Compression Parameters:

Hardness Test:

The hardness of wheat grass tablets was measured using a Monsanto or Pfizer hardness tester. Each tablet was placed between the anvils of the tester, and force was applied until the tablet broke. The breaking force was recorded, and the average hardness was calculated. The acceptable hardness range for sustained or controlled release tablets is 6–10 kg/cm².

Thickness Test:

Tablet thickness was determined using a vernier caliper or micrometer screw gauge. Five to ten tablets were selected randomly and measured individually, and the average thickness was calculated. Uniform thickness indicates proper compression. The typical thickness range for sustained or controlled release tablets is 4.0–7.0 mm.

Weight Variation Test:

Twenty tablets were selected randomly and weighed individually using an analytical balance. The average weight was calculated, and individual weights were compared with the average. The results were evaluated according to pharmacopoeial limits. According to IP standards, tablets weighing less than 80 mg may vary by ±10%, tablets between 80–250 mg by ±7.5%, and tablets above 250 mg by ±5%. Not more than two tablets should exceed the ±5% limit, and none should exceed ±10%.

Friability Test

Performed using a Roche Friabilator at 25 rpm for 4 minutes. This test measures the tablet's physical resistance to abrasion. For these specific coated formulations, weight loss should remain below 1%, with typical values ranging from 0.4% to 0.6%.

Disintegration Test

Conducted in a USP apparatus using a pH 6.8 phosphate buffer at 37 ± 2°C. The test monitors the time required for the tablet to break down completely.

Results: The 5:5 (S+L) ratio showed the highest resistance (>2 hours), while the 6:4 ratio disintegrated fastest (1:10 hours).

Dissolution Study

Carried out via USP Apparatus-II (Paddle Method) at 50 rpm in 900 ml of pH 6.8 buffer (37 \pm 0.5°C). Samples were collected over 12 hours, replaced with fresh media to maintain volume, and analyzed using UV-spectrophotometry to determine the drug release profile.

In-Vitro Drug Release Profile of Tablets at Different pH Conditions